CENTER FOR NEUROBIOLOGICAL SCIENCES 
University of Florida
Gainesville, Florida
Director: Charles J. Vierck
Department
of Neuroscience
Co-Director: Carol Van Hartesveldt
Department of Psychology
The purpose of the Center for Neurobiological Sciences is to
coordinate, encourage and support interdisciplinary research and education
on the nervous system. The Center is made up of faculty and students from
a variety of departments, including physiology, pharmacology, neurology,
neurosurgery and ophthalmology (in the College of Medicine), oral biology
(in the College of Dentistry), physiological sciences (in the College of
Veterinary Medicine), pharmacodynamics (in the College of Pharmacy) and
psychology (in the College of Liberal Arts and Sciences). In addition,
the Center is affiliated with the Whitney Laboratory of the University
of Florida, located at Marineland, Florida. The Center sponsors a local
neuroscience meeting in the fall and a regional neuroscience meeting in
the spring. A number of outstanding speakers are brought in throughout
the year, and travel support is provided for students and faculty to attend
meetings and present their work or to acquire new technical skills. The
Center supplements departmental offerings by contributing several courses
in the neurobiological sciences, and forums are provided for students to
gain experience with oral and written presentations of their scientific
interests.
Included in this brochure is a list of Center members and a description
of their research interests. For more information, write the Director,
Center for Neurobiological Sciences, PO Box 100244, Medical Sciences Building,
University of Florida, Gainesville, FL 32610.
Program of Study
The Center does not admit students into Ph.D. programs; these are offered
through the departments in which members of the Center have appointments.
The purpose of the Center is to enhance these departmental curricula by
providing broad perspectives and interdisciplinary research experiences
in the neurobiological sciences. Courses in a variety of departments are
available, and students are encouraged to design a tailored curriculum
of courses as part of their interdisciplinary program.
Research Facilities
Excellent facilities for research in all areas of neuroscience and behavior
are available in departmental laboratories in the Health Center Complex,
Psychology Building, the adjacent Veterans Administration Medical Center,
the nearby Animal Research and Primate Research facilities, and the Whitney
Laboratories. Both the main campus and College of Medicine libraries have
extensive holdings.
Financial Aid
Research and teaching assistantships are available through the various
departments, and the Center provides stipends, through a training grant,
to advanced students whose advisors are members of the Center. Fellowships
are also available from the Graduate School for minority students.
The University
The University of Florida is a combined state university and land-grant
college with an approximate enrollment of 35,000. The Colleges of Medicine,
Dentistry and Veterinary Sciences, the Institute of Food and Agricultural
Sciences, the School of Law, and the Graduate School are located on the
campus, along with the undergraduate colleges. The graduate school offers
programs leading to the Ph.D. in 56 fields. The campus is located in Gainesville,
a community in north central Florida. The Whitney Laboratory is located
on the east coast, at Marineland, just south of St. Augustine.
Application
Application for admission must be made through degree-granting departments
whose faculty are members of the center. After deciding which faculty member
and/or department is of interest to the applicant, it is suggested that
the applicant write to that faculty member and the graduate coordinator
of the department, informing them of an interest in the program. The departments
are listed below; address for all departments is the University of Florida,
Gainesville, Florida 32610.
Department of Neuroscience, College of Medicine, Box 100244, JHMHC.
Department of Pharmacodynamics, College of Pharmacy, Box 100487, JHMHC.
Department of Pharmacology and Therapeutics, College of Medicine, Box
100267, JHMHC.
Department of Physiology, College of Medicine, Box 100274, JHMHC.
Department of Physiological Sciences, College of Veterinary Sciences,
Box 100144, JHMHC.
Department of Psychology, College of Arts and Sciences, 114 Psychology
Building (Zip Code: 32611-2065).
RESEARCH INTERESTS OF FACULTY MEMBERS OF THE CENTER FOR NEUROBIOLOGICAL
SCIENCES
Barry W. Ache, Ph.D., Professor, Whitney Laboratory:
We are interested in the sense of smell. Odors are complex blends of molecules
that are discriminated on the basis of the unique patterns of discharge
they create across the ensemble of neurons. We are currently attempting
to elucidate the neural mechanisms that shape these patterns and thereby
form the code for odor quality. For much of our work we use non-vertebrate
models, in particular the spiny lobster. There is evidence for more than
one transduction mechanism in the same lobster olfactory receptor cell.
We are also interested in describing the pattern of connectivity between
receptor cells and their central target neurons in the glomerular neuropil
of the olfactory lobe and how synaptic interactions among neurons within
the olfactory lobe contribute to odor recognition. These studies combine
intracellular recording and staining with pharmacological and immunocytochemical
techniques.
Trainee Participation in this Research: Students are trained
primarily in electrophysiological techniques using patch clamp technology.
This training is supplemented with further training in either molecular
biology, second messenger biochemistry or immunocytochemistry, depending
on the demands of the specific project. The latter skills are provided
through specific collaborative arrangements between the parent lab and
three of the research groups in the highly active Whitney Lab.
Douglas K. Anderson, Ph.D., Department of Neuroscience:
At the present time there are two primary goals of this laboratory.
The first is the use of transplantation of fetal neural tissue as one approach
to improve locomotor performance in chronically spinal cord injured animals.
The second is the study of secondary injury following trauma to the CNS.
Particular emphasis is placed on the role of free radicals, lipid peroxidation
and the inflammatory process in the genesis of this secondary injury and
the capacity of antioxidant and antinflammatory compounds to limit this
injury and to restore neurological function following injury.
Kevin J. Anderson, Ph.D., Assistant Professor, Physiological Sciences
and Neuroscience: The primary focus of my laboratory is the characterization
of excitatory amino acid (e.g. glutamate) systems in the brain of aged
rodent, non-human primate and human. In particular, our objective is to
understand the relationship between excitatory amino acid systems and neuronal
death during aging or neuropathology. For these studies, I use quantitative
receptor autoradiography to study the anatomy, pharmacology and kinetics
of excitatory amino acid receptors and transporters in the aged brain.
In addition, I examine the effects of brain lesions and resultant neural
plasticity mechanisms on these systems. Finally, I am interested in the
role that astrocytes play in regulating the transport of potential excitotoxins
and how astrocytes function during aging and disease.
Trainee Participation in this Research: Trainees are involved
directly in the research described above. Other techniques used: immunohistochemistry,
in situ hybridization
Peter A.V. Anderson, Ph.D., Professor, Whitney Laboratory: We
are using conventional electrophysiological and molecular biological techniques
to characterize ion channels in a variety of lower animals. This is being
done partly in an attempt to trace the evolution of ion channels, and ultimately
the nervous system, and partly because this work may provide important
structure/function information about the ion channels in higher organisms.
In addition, we are using similar techniques to study chemical synaptic
transmission in a jellyfish. The synapse in question is unusual inasmuch
as it is bidirectional, but has the advantage that its structure permits
simultaneous pre- and post-synaptic voltage clamp recordings. Thus, this
work may provide important information about chemical synaptic transmission,
in general.
Trainee Participation in this Research: The research carried
out in my laboratory employs a variety of electrophysiological, biochemical
and molecular biological techniques. These include (electrophysiology)
intracellular recordings, whole cell, and single channel patch clamp, and
two electrode voltage clamp. The biochemical techniques include protein
and lipid purification, and characterization using TLC, SDS-PAGE and western
blotting. The molecular biological techniques employed include cDNA library
production, PCR, cDNA cloning and DNA sequencing. Trainees resident in
my laboratory would be trained in which ever techniques was required for
their research but would, in addition, be exposed to all other techniques
through group discussions, tutorials and, if possible, through practical
experience.
Barbara-Anne Battelle, Ph.D., Associate Professor, Neuroscience
and Whitney Laboratory: The responsiveness of photoreceptors
to light can be modulated by messages from the brain and by light itself.
We are examining the molecular mechanisms underlying the photoresponse
and its modulation. Our experimental animal is the horseshoe crab Limulus
polyphemus; in this animal a well characterized centrifugal projection
from the brain to the eyes regulates the responsiveness of the photoreceptors
to light in a circadian manner, and the effects of light on photoreceptor
sensitivity are well documented. Our experimental approach is largely biochemical
and anatomical. We are identifying the neuroactive molecules released from
the centrifugal neurons onto the photoreceptors and the intracellular messenger
systems activated by centrifugal input and by light. We also use the tools
of molecular genetics to characterize protein substrates. Our goals are
to understand the basic processes of phototransduction and adaptation,
and, more generally, to understand how intracellular messenger systems
interact to modulate cell function.
Trainee Participation in this Research: A multiple disciplinary
approach is used in our research efforts. The tools of molecular genetics
are applied to clone and sequencing cDNA encoding proteins of interest
and to begin to understand the functions of these proteins. Modern techniques
or protein chemistry are applied to compare the properties of the native
proteins with those expressed recombinant proteins. Biochemical assays
are used to study the mechanisms of transduction and adaptation; immunocytochemistry
is applied to locate the protein products.
W. Keith Berg, Ph.D., Professor, Psychology: Our laboratory
is focused on the study of the psychophysiology. In general, this area
is concerned with the association of the psychological events with changes
in bodily and brain physiology. It typically involves study of intact humans,
although it can be carried out with animals as well. Response measures
can include brain electrical events (such as EEG, and event related potentials),
cardiovascular events (such as heart rate, blood pressure), other autonomic
events (such as skin conductance), or electrical changes in muscles. In
our laboratory we have focused on changes in heart rate, brain wave and
muscle activity (startle blinks) during a variety of situations with both
adult and infant populations. Our current interests center on physiological
changes that accompany a subjects's anticipation of an interesting and/or
important event. It is similar to but not identical with classical conditioning.
We have also carried out studies of modulation of startle and other reflexes
by previous acoustic and visual events. Finally, we have studied the effects
of "visual stress," as measured by facial muscle changes, of individuals
observing computer monitors of various quality for sustained periods. All
of these areas have received funding from both federal and private sources
over the years. Though most of our work is with humans, we have studied
both infant and adult rat startle reflexes and heart rate as well.
Trainee Participation in this Research: Trainees in this
laboratory learn a wide variety of research skills. Laboratory skills taught
include the appropriate choice, location and method of attachment of external
electrodes for the recording of heart rate, electromyogram, and electroencephalograms
and other physiological measures. In addition trainees are taught the use
of appropriate physiological amplification and transduction equipment,
and the use of the latest computer software and hardware for the display
and processing of the data. Off-line data analysis procedures will also
be demonstrated including statistical packages (e.g., BMDP), spreadsheets
(e.g., Quattro) and custom data scoring programs. Trainees would normally
be fully involved in the execution of all phases of a complete research
study with infants, young children or adult human subjects.
Donald C. Bolser, Assistant Professor, Physiological Sciences and
Neuroscience: Our laboratory is actively engaged in the study of pulmonary
defensive reflexes, such as the cough reflex, which are essential for maintenance
of normal lung function. We have two main efforts ongoing. First, we are
attempting to determine the mechanism of action of centrally-active cough
suppressant (antitussive) drugs. Using a combination of pharmacological
and physiological methods, we have determined that these drugs suppress
the cough motor pattern in a very specific manner. Our results suggest
that a central ?gating? mechanism exists that regulates afferent input
to the central pattern generator for cough (located in the brainstem).
This gating mechanism is sensitive to the suppressive effects of antitussive
drugs, but the central pattern generator for cough is not. The location
and characteristics of the neurons that contribute to the gating mechanism
are currently unknown and remain a primary focus of this laboratory. Our
second research effort is aimed at determining the mechanisms by which
pulmonary defensive reflexes are impaired after cervical spinal injuries
and the identification of strategies that will restore their function.
In animal models, we have determined that these reflexes are functionally
resilient to moderate cervical spinal injuries involving the phrenic motor
nucleus. Elucidation of the mechanism by which motor drive to respiratory
muscles is maintained in the face of cervical spinal injuries is a major
goal of this research.
Trainee Participation in This Research: The trainee will be expected
to master a variety of physiological and pharmacological methods including
but not limited to: electromyogram and neurogram recordings, single and
multiple unit recording methods in the brainstem and spinal cord, advanced
correlational and spike triggered averaging analysis of single neuron spike
trains, and selective delivery of drugs to the central nervous system.
Participation in research conducted in this laboratory will also involve
familiarity with animal models of spinal injury and methods of cellular
repair of spinal tissue and animal models of cough. The graduate student
also may have the opportunity to participate in experimental work involving
humans.
Marc N. Branch, Ph.D., Professor, Psychology: Behavioral
factors involved in modulation of effects of prolonged, repeated exposure
to cocaine. Effects of immediate, brief signals on performance maintained
by delayed reinforcement. Observing responses and attention.
Trainee Participation in this Research: Students learn to employ/investigate
principles of operant and respondent conditions. They also learn basics
of pharmacological techniques.
Brian Y. Cooper, Ph.D., Assistant Professor, Oral & Maxillofacial
Surgery: Research in the neurophysiological laboratories of the
Dept. of Oral and Maxillofacial surgery is concerned with the development,
maintenance and control of inflammatory pain. These questions are addressed
in two acute preparations. In one preparation, recordings are made from
the trigeminal root ganglion of neural activity originating in the palatal
tissues. Examination of the evolution of stimulus-response properties of
thin fiber afferents are made following exposure to local and blood borne
hormones and immune system by-products. In a related series of experiments,
recordings in the trigeminal root ganglion examine the properties of afferents
in the temporomandibular joint. Currently, the goat is used as a subject
in both cases.
Trainee Participation in this Research: Other techniques used:
Students in my laboratory learn general electrophysiological and surgical
dissection techniques; In addition they are trained in the anatomy, physiology
and pharmacology of the pain system; modes of interaction between the immune
system and the pain system; and the biomechanics of soft tissues.
Paul W. Davenport, Ph.D., Associate Professor, Physiological Sciences:
Research in my laboratory combines invasive studies on animals with non-invasive
human experiments to develop an understanding of the role of the cerebral
cortex in respiratory sensations and the control of breathing. The transduction
properties of respiratory muscle afferents are under investigation with
the correlation of muscle mechanics with afferent discharge. The central
projections of these afferents are studied electrophysiologically by recording
thalamic and cortical neurons that are activated by respiratory muscle
afferents. Cortical evoked potentials elicited by loads to breathing and
psychophysical measures are used as a tool for studying respiratory sensation
in humans. Respiratory load sensation is studied in adults, children and
asthmatic patients. Psychophysical and evoked potential studies are being
used with asthmatic patients that have difficulty sensing their asthmatic
attack. The combination of the animal and human studies allows for identification
of the neural mechanisms of respiratory load sensation and the related
adjustments to breathing mediated by the cerebral cortex.
Trainee Participation in this Research: Graduate students learn
respiratory and neurophysiological methods during the course of training
in this laboratory. Specific methods related to respiratory physiology
include lung volume, airflow and pressure recording in humans and experimental
animals for tracheostomy, arterial and venous cauterization, exposure of
respiratory muscles, spinal laminectomy and craniotomy must be mastered.
Electrophysiological techniques are used for recording single unit activity
form peripheral nerves, dorsal rootlet recording, extracellular microelectrodes
recordings in the central nervous system, brain surface electrode recording
and muscle electromyography, In humans, skin electrodes are used for recording
brain evoked potentials and muscle activity. Psychophysical methods are
used in human studies of respiratory sensation. The physiological parameters
recorded in these studies are processed by appropriate computer analysis.
Graduate students are expected to have both human and experimental animal
experience before they complete their training.
Ralph Dawson, Jr., Ph.D., Associate Professor, Pharmacodynamics:
My laboratory is currently involved in examining the role of excitatory
amino acids in mediating neuronal cell death. Specifically, we are interested
in glutamate and aspartate and their role in age-related neuronal loss
and neurodegenerative diseases. We are examining the enzyme glutaminase,
which is responsible for the synthesis of neurotransmitter glutamate and
ammonia, which are neurotoxic in excessive concentrations. The second area
we are investigating is the release of glutamate by conditions that compromise
the energy levels of neurons. We have evidence to suggest that under conditions
of ATP depletion or mitochondrial inhibition, excessive amounts of glutamate
are released. These two related processes, glutamate synthesis and release,
are known to be involved in many neurological disorders such as Alzheimer's
disease, Huntington's disease and stroke. Our studies seek to examine their
role in the neuronal death that accompanies "normal" aging. My laboratory
is also interested in the role of taurine in protecting the brain from
the neurotoxic actions of excitatory amino acids. We have found that taurine
levels in the blood decrease in aging and may contribute to the vulnerability
of the brain to various neurotoxic insults. We are currently exploring
the possibility that dietary taurine could ameliorate or attenuate the
age-related loss of neurons.
Trainee Participation in this Research: This laboratory conducts
basic neurochemical studies of excitatory amino acid neurotransmission.
Research training is available in in vitro techniques for neurotransmitter
release from brain slices, synaptosomes and glial cultures, other techniques
available include; high affinity amino acid uptake measurement, radioligand
binding and detailed enzymatic studies including enzyme purification. The
basic approach involves neuropharmacological analysis of how excitatory
amino acid synthesis and releases are controlled. The laboratory also has
extensive experience in analytical neurochemistry using high performance
liquid chromatography.
William W. Dawson, Ph.D., Professor, Ophthalmology: Research
continues into the investigation of the relationship between cell layers
of the retina, their electrical signals and their morphology. Current specific
interest lies in the analog potentials produced by pattern stimulation
of the retina and inhibitory influences upon it. Several comparative projects
are ongoing in the laboratory; of particular interest are the anatomical
and physiological studies of human related disease in monkeys (macular
degeneration) and dogs (glaucoma).
Trainee Participation in this Research: Techniques learned include
histopathology, Fourier analysis, analog recording/A-D conversion, fluorescein
angiography, fundus photography and image processing.
Gerhard Freund, M.D., Professor, Medicine and Neuroscience:
The long-term interest of this laboratory is in the effects of aging, of
chronic exposure to alcohol and of Alzheimer's disease (AD) on synaptic
receptors in human postmortem brain. We currently focus on excitotoxic
amino acid receptors, both NMDA and non-NMDA subtypes, because alcohol
has profound effects on these receptors in various in vitro and animal
preparations. Using autoradiographic (in collaboration with Dr. Kevin Anderson)
and membrane preparations we examine the effects of aging, alcohol and
AD upon receptor densities, affinities, distributions within brain structures,
responses to in vitro transmitters and drugs (agonists, antagonists, co-regulatory
sites) and to membrane fluidization. The brains in our collection were
dissected and examined histologically be the neuropathologist Dr. William
Ballinger to confirm the clinical diagnosis of Alzheimer's disease and
to determine if these brains are free of other diseases. Since many clinical
and postmortem conditions also could potentially affect synaptic receptors,
the morphological, clinical and neurochemical data are stored in a computerized
data bank to determine the effects of variables such as autopsy delay,
CNS-active medications taken by the patient and of various clinical conditions
associated with acute and chronic hypoxia.
Trainee Participation in this Research: 1. Preparation of microscopic
sections for autoradiography and electron microscopy of human brain tissues.
2. Quantitative receptor autoradiography. 3. Computer image analyses 4.
Homogenization of tissue samples, liquid scintillation of membrane preparations
5. Statistical analyses using SAS
Jiangu Gu, Ph.D., Assistant Professor, Oral and Maxillofacial Surgery:
We are interested in cellular and molecular mechanisms of somatosensory
transmission and modulation. Sensory signals involving touch, temperature,
and pain sensations are usually initiated on dorsal root ganglions (DRG)
and conveyed to the spinal cord dorsal horn through the release of glutamate
and neuropeptides. These neurotransmitters activate their receptors on
dorsal horn neurons of the spinal cord and result in the changes of postsynaptic
currents or potentials. We propose that an enhancement of synaptic
transmission at this first sensory synapse is critical in the development
of pathological pain. We are currently attempting to elucidate the
mechanisms that potentiate the release of glutamate and neuropeptides from
DRG presynaptic terminal. We are focusing on presynaptic ligand-gated
ion channels, including ATP P2x receptors, kainate receptors, and NMDA
receptors. We are also interested in postsynaptic modulation of glutamate
receptors. Techniques used in our laboratory include
electrophysiological approaches with patch clamp, calcium imaging, immunohistochemical
methods.
Trainee Participation in this Research: Students will be
trained primarily in patch clamp techniques. This training is supplemented
with further training in immunocytochemistry and/or calcium imaging, depending
on the demands of the specific project.
Jeffrey K. Harrison, Ph.D., Assistant Professor, Pharmacology:
Our laboratory is interested in the molecular characterization of G-protein
coupled receptors. Collectively these receptors form a large superfamily
of genes whose encoded proteins are characterized structurally as having
seven stretches of hydrophobic amino acids that are capable of spanning
the plasma membrane. Functionally, they mediate the actions of a wide variety
of hormones, neurotransmitters, and drugs. Our research
is focused primarily on receptors for chemokine (chemoattractant cytokine)
peptides. We use a variety of experimental approaches with the goal to
understand the location of expression and cellular signaling mechanisms
of these receptors. Techniques in the lab include pharmacological, biochemical,
immunological, and molecular biological methodologies.
Most of our attention is focused on determining the functional role
of chemokines and their receptors in the
central nervous system. Chemokines are a class of pro-inflammatory
peptides that are important mediators of
leukocyte migration. We have identified a number of chemokine receptors
in the rat and have determined that
the central nervous system expresses many of these genes. Chemokine
receptors are being studied in
transfected mammalian cells, primary cultured cells derived from rat
brain (i.e. microglia, astrocytes, and
neurons), as well as a number of neuroimmunological animal models.
My laboratory actively collaborates with a number of research groups
here at UF as well as at other
institutions. My principal collaborators outside of UF are Drs. Lili
Feng (The Scripps Research Institute, La Jolla,
CA) and Kevin B. Bacon (Neurocrine Biosciences, San Diego, CA). We
are also working with Dr. Faye
Silverstein (University of Michigan). At UF our group interacts extensively
with Drs. Wolfgang J. Streit
(Neuroscience), Luiz Belardinelli (Medicine), Maureen M. Goodenow (Pathology),
Richard W. Moyer (Molecular
Genetics and Microbiology), and Craig H. Gelband (Physiology).
Marieta B. Heaton, Ph.D., Professor, Neuroscience: The
research in my laboratory is concerned with both normal nervous system
development and abnormal development produced by prenatal exposure to neurotoxins.
We are examining the role played by various normally occurring growth factors
in fostering survival and differentiation of developing neuronal populations.
We are using chick embryos and fetal rats to study the damage that neurotoxins
such as alcohol can cause in the developing nervous system. Such prenatal
exposures leads to the Fetal Alcohol Syndrome (FAS) in both humans and
in animal models. We are investigating the possibility that synthesis of
vital growth factors such as nerve growth factor (NGF) is reduced in FAS,
leading to loss of certain responsive neuronal populations. Of particular
interest in this regard is the developing septo-hippocampal system, a system
critical to normal memory and cognitive functioning, a portion of which
is selectively damaged by prenatal alcohol exposure. These studies are
assessing morphological and neurochemical differentiation within cholinergic
and GABAergic basal forebrain populations following prenatal ethanol exposure,
and the concomitant synthesis of NGF and other growth factors within the
hippocampus, their normal projection target. Both in vivo and
in vitro investigations are being performed. An additional line of
research, using a tissue culture model system, is directly viewing cellular
events involved in ethanol neurotoxicity, and assessing the possible modulation
of this toxicity by neurotrophic factors and other substances.
Trainee Participation in this Research: Trainees will be involved
in most phases of research in my laboratory. Among the techniques which
will be learned are paraffin histology, immunohistochemistry, neuroanatomical
quantitative analyses, tissue culture of primary neuronal and non-neuronal
cells, autoradiography, quantitative enzymatic assays (e.g., choline acetyltransferase
assay, ELISA analyses of neurotrophic factors), and bioassays to assess
activity of neurotrophic factors.
Kenneth M. Heilman, M.D., Professor, Neurology: Our laboratory
performs research on the neglect syndrome. The neglect syndrome is an attentional
disorder induced by a variety of lesions and interfere with attentional
processing and response to stimuli. Our research is primarily behavioral
and takes place in three laboratories; a primate laboratory and rat laboratory
on 34th street and a human laboratory at the V.A. Medical Center. For review
of our research, see Neglect in Clinical Neuropsychology, edited
by Heilman and Valenstein, Oxford University Press, 1985.
Trainee Participation in this Research: Students received
in-depth training in behavioral techniques for evaluating sensory capacities
and states of arousal.
Dena R. Howland, Ph.D., Research Assistant Professor, Neuroscience:
The overall focus of the laboratory is to determine how the spinal
cord responds to injury and what interventions may be used to enhance recovery
based upon both anatomical and behavioral criteria. A variety of
lesion models in both the rat and cat are being used. Our studies
have shown that grafts of embryonic spinal cord can promote recovery following
spinal cord injury in both developing and adult systems. These grafts
can survive for long periods and undergo substantial differentiation.
Although grafts into adult and developing systems both integrate with the
host tissue, the grafts integrate more extensively and promote greater
axonal growth when placed into the developing host system. This structural
response difference is correlated with differences in behavioral recovery.
We are continuing to assess the potential for grafts of embryonic spinal
cord to enhance behavioral recovery and promote anatomical repair in the
adult and believe that the mechanisms by which transplants may work in
the adult versus developing system are different. A variety of neuroanatomical
and molecular methods are being used to assess the cellular and axonal
interactions that occur between the host and graft. The behavioral
analysis focuses on several characteristics of locomotion including weight
support, balance, interlimb coordination and angular kinematics.
We are also currently studying the expression of several molecules that
are know to affect axonal growth during development. These molecules
include both growth-promoting and repulsive molecules as well as their
putative receptors (e.g. netrin, proteoglycans, aggrecan, dcc). The
differential display of these molecules in the adult and following injury
may suggest mechanisms that affect growth which are present or absent in
the developing versus adult versus injured systems. These differences
may also suggest potential therapeutic strategies for the adult.
To this end, we are degrading proteins as well as introducing genes to
make proteins within the injured central nervous system. In addition
to repair strategies using cellular and molecular approaches, we are also
evaluating the effects of rehabilitation training paradigms on recovery
in experimental animal models. These studies should begin to indicate
whether training is important, whether the type of training is critical
and whether training can be beneficial, detrimental or benign based upon
behavioral and anatomical criteria.
Richard D. Johnson, Ph.D., Assistant Professor, Physiological Sciences:
The goal of the laboratory is to study the electrophysiology and neuroanatomy
of the single sensory neurons, spinal cord and brainstem interneurons,
and motoneurons involved in (1) the control of the reproductive and pelvic
organs and (2) sense organs in skin and muscle. Current areas of
emphasis involve the investigation of normal mechanisms, sensory and motor
dysfunction following chronic spinal cord or peripheral nerve injury, chronic
pain, and the efficacy of neural transplantation and neurotrophic factor
intervention in the recovery of function.
Trainee Participation in this Research: The laboratory
is designed to perform in vivo electrophysiological experiments on anesthetized
rats. Surgical approaches include intracranial, intraspinal, and peripheral
nerve/muscle. Facilities for performing chronic surgeries on nerve and
spinal cord are present. Single cell recording (intracellular and extracellular)
is performed in the brain and spinal cord as well as in somatic and autonomic
nerves. Other methodology includes computer-interfaced data acquisition/data
analysis, spike-triggered averaging, evoked potential recording, feedback
controlled mechanical stimulation, and iontophoresis are used. Anatomical
procedures on board include light microscopy (histochemistry and immunocytochemistry),
scanning electron microscopy, and transmission electron microscopy. Techniques
for behavioral analysis of male rodent sexual behavior are available.
Pushpa S. Kalra, Ph.D., Professor, Neuroscience: Neuroendocrinology
of reproduction, neuroimmunoendocrinology, neural regulation of sexual
and feeding behaviors in rodents.
The inflammatory cytokines have profound inhibitory effects on the hypothalamo-pituitary-gonadal
axis. We are investigating this action with special emphasis on the hypothalamus.
Our endeavors are concentrated on elucidating the impact of cytokines on
the complex interaction among the neuropeptides that regulate hypothalamic
luteinizing hormone releasing hormone activity. We are especially interested
in the activities of members of the pancreatic polypeptide, the endogenous
opioid peptide and tachykinin families. The overall objective is to unravel
the sequence of interactions among these regulatory neuropeptides as they
alter hypothalamo-pituitary hormonal functions in response to the stress
of inflammation.
The regulation of food intake by neuropeptides is being investigated
with the aim of identifying the effective molecules, mapping the hypothalamic
pathways and assessing alterations in their functional activity to account
for drastically altered feeding patterns leading to hyperphagia and obesity,
especially when it is induced by neural injury and/or neurotoxins.
Brief description of education interests and activities: Coordinator
of Endocrinology Section of Physiology courses for medical and dental students;
lectures in general and reproductive endocrinology. Member Dissertation
Committee for graduate students in the Colleges of Medicine and Pharmacy.
Training of Postdoctoral Fellows in neuroendocrine research.
Satya P. Kalra, Ph.D., Professor, Neuroscience:
The hypothalamus is crucial to homeostatic integration and regulation of
functions essential to survival both of self and species. Clues to understanding
the hypothalamus lie in a complex communication network which continuously
receives, interprets, transduces and transforms information into neural
and hormonal messengers. The goals of our laboratory are to first identify
novel messenger molecules and then study the site and mode of action, and
control of their synthesis and release. State-of-the-art cellular and molecular
biology techniques are employed for accomplishing these goals. Specifically,
the current research is focussed on neuroendocrine aspects of hypothalamic
regulation of pituitary function and brain control of obesity.
Neuroendocrine Research: The long-term goal is to map the route of signal
transmission responsible for the secretion of hypothalamic hormones that
participate in the induction of ovulation and anovulatory infertility.
These investigations include a detailed analysis of the interaction between
inhibitory (opioids and tachykinins) and excitatory (neuropeptide Y, galanin,
agmatine and nitric oxide) messenger molecules.
Brief Description of Other Research Interests and Activities:
Brain Control of Obesity: Since the discovery in this laboratory that
neuropeptide Y is a naturally-occurring appetite transducer, we are continuing
to investigate the role of this signal in induction of obesity. The investigations
include neural and endocrine factors that regulate secretion of neuropeptide
Y in the hypothalamus and underlying molecular mechanisms in the etiology
of neurotoxin- and diabetes-induced obesity and hypertension. Finally,
special attention is paid to the development of suitable agonists and antagonists
for therapeutic application.
Brief description of education interests and activities: Education
efforts include teaching anatomy, neurochemistry and signal modalities
in the hypothalamic control of homeostatic process and pituitary function
to graduate, medical and dental students. Postgraduate education includes
training of postdoctoral fellows in molecular and neuroendocrine aspects
of hypothalamic function.
Michael A. King, Ph.D., Assistant Research Scientist:
Neurobiology of alcoholism, neuroanatomy, neurohistology, limbic system.
Christiana Leonard, Ph.D., Professor, Neuroscience:
I work with an interdisciplinary research team of neuropsychologists, psychiatrists,
and neurologists interested in the diagnosis and treatment of children
with dysfunctional verbal and nonverbal social communication skills. Current
evidence suggests that many of these children have anomalous brain asymmetries
and that their behavioral problems may be due in part to structural neurodevelopmental
defects. We are currently developing neuroanatomical and behavioral assessment
procedures for these children by (a) using digital image analysis and psychophysics
to identify the physical features that make facial expressions so uniquely
salient; (b) refining a category scheme for verbal messages used to define
human social relationships; and (c) using quantitative methods to analyze
magnetic resonance images (MRIs). Our goals are twofold: we hope to develop
rational therapies based on an improved understanding of the underlying
functional disabilities as well as to further our understanding of the
neuroanatomical correlates of functional lateralization.
Trainee Participation in this Research: Trainees develop
behaviorally salient stimuli (facial expressions) and use psychophysical
and other experimental paradigms to assess human information processing
of affective stimuli. They also test patients and controls on a variety
of cognitive and language tests in order to develop subject groups whose
brain morphology is assessed quantitatively. They develop computer programs
to make these assessments and learn enough neuroanatomy to make reliable
measurements of cortical and subcortical structures involved in language
and visual spatial function.
Mark H. Lewis, Ph.D., Associate Professor, Psychiatry, Neuroscience,
and Psychology: The research interests of this lab involve brain-behavior
relationships with a focus on effects of alterations in development and
social experience on central dopamine function. Our studies include investigation
of the neurobiological mechanisms that mediate repetitive behavior disorder
(i.e., stereotypies, self-injury, compulsions) in individuals with mental
retardation. This project, using biochemical, psychopharmacological, and
neuropsychological methods, is examining the hypothesis that these behavioral
disorders are due to a developmental insult to central dopamine and serotonin
systems. We are also examining the long-term neurobiological effects of
early social deprivation in non-human primates. Such early insult results
in life-long alterations in behavior (e.g., stereotypies and self-injury)
and in brain structure and function. Our data to date show that early social
deprivation results in dopamine receptor "supersensitivity" and marked
changes in the chemoarchitecture of the striatum. Finally, we are studying
the neurobiological mechanisms by which genetic, developmental, and experiential
factors influence social behavior in mice selectively bred for high and
low levels of aggression.
Trainee Participation in this Research: Trainees working on these
projects will be able to learn a variety of techniques relevant to the
biochemical basis of behavior including receptor binding methods (homogenate
binding, receptor autoradiography), high performance liquid chromatography
for neurochemical determinations, stereotaxic surgical techniques automated
(e.g., startle) and observational behavioral assessment, tissue sectioning
and microdissection by punch, and in situ hybridization.
Paul Linser, Ph.D., Associate Professor, Whitney Laboratory:
Our studies focus on the regulation of gene expression and cell phenotype
maturation during development. We are currently pursuing two major directions.
First, we are investigating those events in cell-to-cell communication
that influence cell differentiation. In general, cells receive stimuli
from their microenvironments in three forms: soluble molecules, which reach
the cell by diffusion; insoluble molecules, which are fixed to structural
elements of the environment surrounding a cell; and physical contact with
adjacent cells through receptor molecules on cell surfaces. We have identified
cell membrane molecules involved in such communication, and we are now
describing in detail the biochemical characteristics and functional role
of particular cell surface macromolecule first discovered in our laboratory.
Our laboratory is also studying the DNA sequences that regulate the expression
of the gene encoding carbonic anhydrase II (CA-II), an enzyme critical
to cell function. We have found that the pattern of appearance of CA-II
during development is complex, and have theorized that the regulation of
the expression of the CA-II gene, during this period, must follow the same
complex pattern. Using the techniques of molecular genetics, we are now
attempting to test this hypothesis. In addition, we are examining the physiological
role of CA-II in ocular tissues. Our studies are usually performed on cells
and tissues of the visual system including the neural retina, lens, and
optic lobes of the brain.
Trainee Participation in this Research: Technical approaches
available for students to learn in this laboratory include: protein analysis
including SDS-PAGE and Western blotting; molecular analyses of genomic
DNA and mRNA expression including engineering and characterization of antisense-producing
retroviral vectors and plasmids; cell culture; hybridoma production and
characterization; embryo culture; computer-aided analyses of gene and protein
sequence data; immunohistochemistry; computer-aided image analysis.
William G. Luttge, Ph.D., Professor, Neuroscience: Our emphasis
is on the CNS receptors for adrenal steroids. Current projects include
an initial characterization of molecular biological mechanisms mediating
the endocrine and tissue-specific regulation of the expression of genetic
coding for these receptors. Other projects include a continuing analysis
of the physicochemical, protein biochemical and steroid binding properties
of the receptors as well as the molecular mechanisms and consequences of
their transformation (activation) to nuclear/DNA binding species.
Trainee Participation in this Research: Trainee participation
in this research program will often entail training in techniques related
to routine endocrine organ, brain and peripheral target tissue surgical
isolations; routine biochemical, radioreceptor and radioimmunoassay procedures;
routine chromatographic, electrophoretic, ultracentrifugation and in vitro
incubation procedures; and a growing involvement with tissue culture and
various recombinant DNA procedures.
A. John MacLennan, Ph.D., Associate Professor, Neuroscience:
We study proteins involved in brain development and nervous system responses
to injury. By better understanding how the nervous system is put together
during development and how in some rare cases, as in peripheral nerve regeneration,
the nervous system can put itself back together after severe insult, we
expect to contribute to the development of therapies that repair the nervous
system after diseases and injuries that it can not effectively respond
to on its own. Most of our current work examines the role that ciliary
neurotrophic factor receptor a (CNTFRa ) may play in peripheral nerve regeneration.
We have recently discovered that axotomized spinal motor neurons selectively
increase their production of CNTFRa protein and mRNA while they regenerate
their injured axons.
Edwin M. Meyer, Ph.D., Associate Professor, Pharmacology: We
investigate a variety of presynaptic neuronal processes using techniques
that range from molecular biology to behavior, due to the multidisciplinary
nature of neuropharmacology. Much of our recent work has focused on age-related
changes in brain neurons that render them susceptible to pathological conditions
such as Alzheimer's disease. We are interested in developing novel animal
models and drug-regimens that will be useful in understanding human disease
processes and treating them. Several ongoing projects include: determining
how age- or lesion-induced changes in receptor activity regulate the transcription
of mRNA encoding neuropeptides; studying age-related reductions in calcium-triggered
neurotransmitter release; measuring the turnover of membrane proteins that
appear to be affected by Alzheimer's disease; testing several potential
therapeutic treatments for dementia in a new animal model for the disease
and gene-delivery into differentiated neuronal types of cells.
Trainee Participation in this Research: Trainees will learn
a variety of approaches, ranging from molecular biology to behavior. These
approaches include: cloning and subcloning of genes into novel vectors
with activity in postmitotic cells; neurochemical measurements of transmitter
turnover and levels; oocyte mRNA-expression systems for receptors; primary
and transformed cell culture; receptor binding and transduction processes;
and memory related behavior.
Merle E. Meyer, Ph.D., Professor, Psychology: We have
been investigating the neuroanatomical substrates underlying behavioral
inhibition induced by dopamine and by opioid peptides. At present our attention
has focused upon the dopamine D1 and D2 agonists and antagonists injected
directly into the nucleus accumbens, olfactory tubercles and dorsal striatum.
In general, DA agonists increase locomotor activity suggesting that the
DAD1 has a behavioral function. In addition to locomotor activities we
have been interested in behavioral inhibition and associated complex inhibitory
responses, particularly the dorsal immobility responses.
Trainee Participation in this Research: Students trained
in this lab are exposed to all the procedures listed above.
David F. Muir, Ph.D., Associate Professor, Pediatric Neurology and
Neuroscience: Our research in cellular and molecular neurobiology
centers on the interactions of neural cells with extracellular matrix during
development, regeneration, pathology and tumor formation.
In development and regeneration, neuronal growth is guided by signals
presented by glial cells and the extracellular matrix. We find Schwann
cell produce both stimulatory and inhibitory signals for growth cone motility.
We have isolated a chondroitin-, heparan-sulfate proteoglycan produced
by Schwann cells which binds to and inhibits the neurite-promoting activity
of endoneurial laminin. This proteoglycan is assembled into Schwann cell
basal lamina and is greatly upregulated following crush injury of peripheral
nerve. Similarly, inhibitory proteoglycan is abundant in injured spinal
cord and brain. My lab explores therapeutic means to enzymatically
degrade and inactivate inhibitory proteoglycans from injured nervous tissues
with the goal of improving axonal growth and functional recovery. We find
that certain neurons secrete matrix-degrading enzymes which belong to the
gene family of matrix metalloproteinases (MMP). For instance, peripheral
sensory neurons secrete MMP-2 (a type IV collagenase). Furthermore, MMP-2
expression by sensory neurons is upregulated by nerve growth factor. We
hypothesize MMP expression is required for growth cone infiltration of
peripheral target tissues. Additionally, MMP-2 degrades and inactivates
inhibitory proteoglycan, providing a physiological mechanim by which neurons
can forge routes of regeneration. This model of neuronal regeneration
and growth cone penetration of tissues shows striking similarities to molecular
processes implicated in tumor invasion through extracellular compartments.
Research goals in neuro-oncology pertain to the mission of the DNOL
(Developmental Neuro-Oncology Laboratory) and include discovery of cellular
mechanisms involved in glial tumor cell migration, invasion and proliferation.
Using both in vitro and in vivo models, human tumor specimens are established
in culture and examined for the ability to degrade extracellular barriers
and to migrate in response to adhesive matrix components. Tumor fragments
and characterized cell lines are then engrafted in animal hosts and examined
for tumor formation and response to anti-invasive therapies. These
studies are applied to problems of tumorigenesis in developing brain and
in Neurofibromatosis type 1.
Trainee Participation in this Research: Training is provided
in research pertaining to neuronal regeneration or neuro-oncology.
Students in my laboratory become proficient in tissue culture methods as
well as small animal surgery. Models of neuronal regeneration include peripheral
nerve and spinal cord injury and subsequent examination of extracellular
matrix expression, distribution and biological function regarding growth
cone motility. Participants in neuro-oncology projects establish cultures
from human tumor specimens are perform a variety of in vitro assays to
characterize cellular constituents and to assess neoplastic properties.
Roger L. Papke, Ph.D., Associate Professor, Pharmacology & Therapeutics
and Neuroscience: The effects of nicotine on human behavior are
mediated by specific receptors in the brain which are normally activated
by the neurotransmitter acetylcholine. We are interested in studying how
these neuronal nicotinic acetylcholine receptors function as ligand-gated
ion channels. We are identifying parts of the molecule which are involved
with the binding of neurotransmitter and the conformational change associated
with receptor activation.
A second major research focus in the lab is identifying the mechanisms
through which nicotine-like substances can alleviate
some of the learning and memory impairments in animal models of dementia
that resemble Alzheimer's disease. We are also
interested in models of nicotine addiction and developing possible
therapies to help people quit smoking.
Joanna Peris, Ph.D., Associate Professor, Pharmacodynamics:
I am basically involved in studies on how drugs of abuse affect the functional
neurochemistry of the brain. In particular, my lab is working on two projects
in this area. The first studies the effects of repeated cocaine exposure
on GABAergic transmission in nigrostriatal and mesolimbic pathways in the
brain. Previous work attempting to discern the neurochemical basis for
behavioral sensitization to repeated exposure to cocaine has focused primarily
on dopamine and serotonin neurons with equivocal results. there is a strong
GABAergic innervation in both of these regions and it is very likely that
GABA activity in these regions modulates the behavioral responses to cocaine.
We have found that cocaine sensitization is strongly correlated with a
decrease in GABA-A receptor number and function. Cocaine sensitization
may also cause a small decrease in the release of GABA from striatal nerve
terminals as well. When antisense oligonucleotides for the mRNA of subunits
of the GABA-A receptor are injected into striatum, cocaine responsiveness
is increased. Together, these data indicate that changes in GABA transmission
in striatum strongly modulates cocaine responsivity and may underlie the
development of behavioral sensitization to cocaine.
The second set of studies investigates how cocaine may interfere with
the development of tolerance to the locomotor incoordinating effects of
ethanol. So far, we have behavioral evidence that concurrent cocaine exposure
will block the expression of ethanol tolerance. This difference is not
due to pharmacokinetic factors however we are unable to determine whether
the effect is purely behavioral (e.g. cocaine interferes with performance
of ethanol tolerance) or whether it cocaine is actually blocking the cellular
development of tolerance (e.g. interfering with the effects of ethanol
on GABA or glutamate receptors).
Trainee Participation in this Research: Students are trained
to be familiar with four basic types of assays. Behavioral assays include
daily treatment of animals with various routes of ethanol administration
(injection, gastric lavage, liquid diets) or cocaine administration and
assessment of the behavioral effects of these drugs including seizure sensitivity,
stereotypy, locomotion, and simple learned behaviors. Neurotransmitter
release assay involve determination of basal and evoked 3H- dopamine or
3H-GABA release from superfused slices of different brain regions. Receptor
binding assays involve determination of the number and affinity of the
various subtypes of dopamine, GABA and glutamate receptors using both tissue
homogenate filtration methods and quantitative autoradiographic analyses.
Receptor function assays involve determination of the efficacy and potency
of drugs acting at a variety of release-modulating autoreceptors. Determination
of the efficacy and potency of drugs affecting 36CI transport via the GABAA
receptor/chloride ionophore.
M. Ian Phillips, Ph.D., D.Sc., Professor, Physiology:
Research is concerned with the physiological role of peptides in brain
and body functions. Specifically the actions of brain angiotensin II in
fluid balance, reproduction, cyclic timing, neurotransmission and behavior
are investigated. The research also involves the morphology and physiology
of circumventricular organs. We use cellular, molecular, and in vitro
slice recording to whole animal and in vivo studies on peptide levels,
receptors and immune responses.
Trainee Participation in this Research: Students trained
in this lab utilize the procedures described above.
Donald D. Price, Ph.D. , Professor, Oral and Maxillofacial Surgery,
Neuroscience: My laboratories have developed research programs
along several interrelated lines. The first is concerned with the
neurophysiological mechanisms by which pain-related information is encoded
and transmitted within the central nervous system. This line of research
has used electrophysiological single unit recording techniques (both extra-
and intracellular), neural imaging techniques (2-deoxyglucose metabolic
mapping and immunocytochemistry), and psychophysical methods in order to
determine how fundamental psychophysical characteristics of pain are related
to the manner in which pain information is encoded and represented within
the central nervous system. A second line of research has dealt with
the neuropharmacological mechanisms of opioid analgesia, tolerance to opioid
analgesia, and hyperalgesia. This line of research has led to discovery
of a commonality between intracellular mechanisms of opioid tolerance and
mechanisms of hyperalgesia resulting from nerve injury and opioid administration.
Studies of these mechanisms have led to several publications, 6 issued
United States patents and several pending patents in foreign countries.
A third line of research has been concerned with psychological mechanisms
of pain processing and pain modulation. It includes studies of hypnotic
analgesia, placebo analgesia, and neurophysiological studies that help
to characterize the neural mechanisms associated with human pain and pain
modulation. The latter include both neuroimaging and human reflex
studies of pain.
Trainee Participation in this Research: At present, trainees
in this research would receive training in psychophysical methods and in
designs of psychological studies to analyze mechanisms of placebo analgesia
as well as NMDA receptor and opioid receptor mechanisms of pain and analgesia
in human subjects. Studies of pathophysiological mechanisms of chronic
pain conditions, such as fibromyalgia, are also ongoing. The possibility
also exists for neural imaging studies of normal and pathological pain.
Philip Posner, Ph.D., Professor, Physiology: The focus
of research in this laboratory is electrophysiology at the whole body,
organ, tissue and single cell level. Current research is focused on the
role of neuromodulators and peptides in regulating electrical activity
in a variety of cell types including neurons, cardiac myocytes, glia and
endothelium using patch clamp techniques. The major aim is to define the
unifying electrophysiological mechanisms which exist in different cell
types for triggering and modulating cell function through electrophysiological
activity.
Trainee Participation in this Research: The focus of research
in this laboratory is electrophysiology, biophysics and signal transduction.
Students in the laboratory participate in studies involving electrical
recordings from excitable tissue. Techniques involve a range from extracellular
recordings, to transmembrane microelectrode recordings, to whole cell patch
clamp recordings, to single channel recordings, We also carry out intra-
and extracellular perfusion to study signal transduction. We are also involved
in cell culture and hope to move into the area of genetic modification
of channels and receptors and incorporation of these into oocytes for electrical
studies.
Mohan K. Raizada, Ph.D., Professor, Physiology: Cell physiology
and molecular biology of neuroendocrine system. In particular, regulation
of neuropeptides such as IGF, insulin and angiotensin and their receptors
in the CNS from normal and hypertensive animals at transcriptional and
translational levels is currently under investigation. In addition, the
role of astrocytes and chemical signals generated by them in the control
of neurotrophic and neuromodulatory functions neurons is an intense area
of study.
Trainee Participation in this Research: Cell culture for normal
and diseased brain (hyperactive rat, Batten diseased brain). Receptor analysis,
kinetics, pharmacology, Western blot. Molecular biology of the endocrine
system; Southern, Northern, PCR, cloning. protein chemistry, sequencing,
Ab production, gel electrophoresis.
Roger L. Reep, Ph.D., Associate Professor, Physiological Sciences:
Our research is focused on comparative neuroanatomy and the evolution of
mammalian cerebral cortex, and on manatee biology. The neural studies
utilize axonal tracers, stains and histochemistry at the light microscope
level, and computer-based image analysis for morphometry, densitometry
and three dimensional reconstruction. Current projects include: 1)
Field studies and neuroanatomical analysis of tactile hairs on the bodies
of Florida manatees. We hypothesize that these hairs are utilized
to detect underwater pressure waves produced by approaching animals, water
currents and tidal flows, and large objects in the environment. 2)
Architectural studies of manatee cerebral cortex. We are using three
dimensional reconstruction to map the extent of presumptive somatic sensory
cortex, and to obtain accurate counts of Rindenkerne, neuronal clusters
in cortical layer VI, each of which we hypothesize processes information
from a single tactile hair. 3) Manatee reproductive hormones and
cyclical mating behavior. Fecal radioimmunoassay procedures and behavioral
analysis are being applied to study seasonal patterns of reproductive biology
in Florida manatees. 4) Biomechanics of manatee bone. We are
quantifying the amount of force required to inflict the damage typical
of fatal boat impact injuries in Florida manatees. Such information
will be critical in establishing boat speed zones adequate to minimize
the chance of fatal impacts. Experiments include assessment of age,
sex, and reproductive status categories; 3-point bending tests; histological
analyses to investigate the mechanism by which pachyostosis occurs; and
measuring mechanical properties of soft tissues overlying bone, to calculate
impact energy transfer to bone. The data obtained from these projects
will allow modeling of manatee/boat interactions, and will contribute significantly
to our knowledge of the physical and physiological effects of boat strikes
on manatees. 5) Cortical circuitry for directed attention behavior
in rats. The rat is being utilized as a model system to study the
neural substrates involved in hemispatial neglect. These studies
involve neuroanatomical, behavioral and neuropharmacological approaches,
currently focused on the dorsocentral striatum, a convergence zone for
corticostriatal inputs.
Trainee Participation in this Research: Most students in
my laboratory learn the following techniques in connection with tracing
neuronal connections in rats: stereotaxic surgery and intracerebral delivery
of axonal tracers, cardiovascular perfusion, histological processing including
a variety of staining procedures, epifluorescence microscopy, neuroanatomical
analysis of connection patterns, and photomicrography. In addition,
image analysis is utilized for quantification of various morphometric and
densitometric parameters, and for three dimensional reconstruction.
Some students in my lab will become conversant with the comparative approach
to studying the evolution of mammalian brains. We are also involved in
behavioral assessment of spatial orientation in rats, social and mating
behaviors in manatees, and use of the postcranial tactile hairs in manatees.
Paul J. Reier, Ph.D., Professor, Neurosurgery: The primary emphasis
of this laboratory is on cellular dynamics and interactions associated
with nerve tissue damage and regeneration. A specific area of interest
in this regard centers upon spinal cord injury and the use of neural tissue
grafts to foster functional sparing and/or recovery in lesion models that
closely parallel the human clinical condition. A wide range of contemporary
anatomical methods (e.g., immunohistochemistry, nerve fiber tracing techniques,
electron microscopy) are being used to elucidate the capacity of donor
and host nerve cells to form connections that could result in better functional
outcomes. In addition, collaborative interactions have been established
with other laboratories in the Center for Neurobiological Sciences that
are aimed at functional evaluation of host-neural graft interactions using
electrophysiological and behavioral paradigms. Closely linked to these
studies of neural grafts, are other studies focused on transplantation
immunology. Experiments are being conducted to assess which cell types
are involved in antigen presentation that can lead to graft rejection.
Coordinated with these in vitro studies are tissue culture projects which
examine cellular interactions that can either enhance or inhibit nerve
fiber growth. The use of cultured cells or their biosynthetic products
to promote regeneration in the central or peripheral nervous system is
also being investigated. A future direction of this laboratory will entail
the use of genetically-engineered cells for transplantation. Thus, a multidisciplinary
approach is being taken to address a major and enigmatic biomedical problem
of considerable basic science and clinical interest.
Trainee Participation in this Research: This research program
embraces several areas of technical expertise to which all students associated
with this laboratory are exposed. The main area of emphasis is on neuroanatomical
methodologies such as: immunohistochemistry, conventional histology, neuroanatomical
tracing methods, and electron microscopy. This is an important aspect of
the program as it introduces students to the basic cell biology of CNS
injury and issues that need to be addressed in order to foster functional
recovery. Another part of the research effort is now focused on behavioral
analysis related to fore- and hindlimb locomotion. A third area of interest
in this laboratory centers on tissue culture methods for studying cell-cell
interaction in vitro or for preparing specific cellular populations
for transplantation. New directions also are becoming defined in relation
to molecular and immunological approaches. For this purpose, postdoctoral
fellows are currently being recruited who will be available for graduate
student training in my laboratory.
Louis A. Ritz, Ph.D., Associate Professor, Neuroscience and Neurosurgery:
The major emphasis of our laboratory's research efforts has centered on
the neurobiological organization of the cat sacrocaudal spinal cord, the
portion of the neuraxis that controls the tail. The sacrocaudal spinal
cord has served as a model to study the relationship of the spinal cord
to midline structures (i.e., neck, truck) of the body, because little is
known about spinal cord control of axial musculature and how this control
is affected by spinal cord injury. Our laboratory is involved in investigations
of. 1) the projection patterns of small-diameter primary afferent fibers
containing calcitonin gene-related peptide (CGRP), in the normal and unilaterally
rhizotomized animal; 2) the intersegmental organization of the spinal cord,
relative to tail-hindlimb interactions and to the behavioral effects of
sacrocaudal spinal cord lesions; and 3) the effects of fetal spinal cord
transplants into the circuitry of the sacrocaudal spinal cord. Quantitative
behavioral analyses have suggested that the segmental reflex functions
of the tail are altered by the presence of fetal transplants. Most
recently, our research efforts are aimed at understanding the effects of,
and the underlying mechanisms involved with, training (activity-dependent
plasticity) of locomotor tasks on interlimb coordination, following thoracic
spinal cord injury. Through functional evaluation of a specific motor function
(forelimb-hindlimb coordination) and neurophysiological evaluation of ascending
and descending aspects of intersegmental (cervical-lumbosacral) connectivity,
we are beginning to assess potential neurobiological mechanisms that may
underlie training effects.
Trainee Participation in this Research: Techniques that
are available in our lab are concerned with anatomical, physiological and
behavioral evaluation of the normal and the injured spinal cord. Most notably
are: 1) intra-axonal staining of physiologically identified primary afferent
fibers, dorsal horn neurons and motoneurons; 2) physiological recording
from the spinal cord, ranging from surface recordings and ventral root
potentials to intracellular recordings from motoneurons and dorsal horn
cells; 3) transplantation of fetal tissue into sacrocaudal spinal cord,
in collaboration with Dr. Paul Reier; 4) anatomical evaluation of the integration
of fetal tissue with the adult spinal cord; and 5) behavioral analyses
of the effects of sacrocaudal lesions and of transplants into the sacrocaudal
spinal cord, in collaboration with Dr. Charles Vierck.
Neil E. Rowland, Ph.D., Professor, Psychology: Main interests
are in the physiology and neurochemistry of feeding, thirst, and sodium
appetite in rodents. Current research includes: 1) The role of brain serotonin
in satiety. 2) Role of renin-angiotensin system in thirst and sodium appetite.
3) Postingestional factors in termination of water intake. 4) Immediate
early gene expression for functional mapping. 5) Relationship between salt
intake, genetic background and development of hypertension.
Trainee Participation in this Research: Students will learn
how to take biological samples in relation to behavioral changes. They
will learn chemical assays including receptors autoradiography, immunocytochemistry,
and radioimmunoassay. Surgical methods include stereotaxic, and various
peripheral (e.g., gastric, venous) surgeries, as needed.
Susan L. Semple-Rowland, Ph.D., Associate Professor, Neuroscience:
The aim of my research program is to understand basic mechanisms underlying
retinal dysfunction and degeneration. We are using molecular and biochemical
techniques to study the cascade of cellular events triggered by genetic
mutations that disrupt photoreceptor function. Currently, the main thrust
of our research effort is directed toward understanding photoreceptor dysfunction
and degeneration in the rd (retinal degeneration) chicken model of inherited
retinal disease, a model for Leber congenital amaurosis, type 1 in humans.
There are two major projects in progress in my laboratory: (1) development
of a lentiviral-based gene therapy for rescue of the inherited retinal
degeneration in the rd chicken; (2) analyses of circadian clock mechanisms
in retinal photoreceptor cells. Several different experimental techniques
are being employed, the majority of which are based on molecular biology.
Trainee Participation in this Research: Students in my
laboratory currently have the opportunity to learn and use the following
techniques in their research studies: Molecular biology techniques: cDNA
cloning, cDNA and genomic library screening, DNA sequencing, PCR, quantitative
reverse transcription PCR, Northern and Southern blot analyses, primary
retinal cell culture, transient transfection analyses of promoter function,
various aspects of viral-based gene therapy. Biochemical techniques: SDS-PAGE,
two-dimensional gel electrophoresis, Western blot, immunocytochemistry.
Gerard P.J. Shaw, Ph.D., Assistant Professor, Neuroscience:
I am interested a complex array of structural proteins known as the cytoskeleton.
In neurons, these proteins are responsible for the growth and regeneration
of axons and dendrites, the transport of material within neurons and the
formation and maintenance of neuronal morphology. The major component of
the neuronal cytoskeleton is a complex of 10nm diameter filaments, called
neurofilaments. These structures are composed of at least 7 different proteins,
the expression of which is controlled in complex ways in development and
disease states. Almost nothing is known about how the neurofilaments are
cross-linked, how they are transported down axons and dendrites and how
they interact with other components of the neuron. All of these questions
are interesting and potentially medically important; alterations in the
organization and expression of neurofilaments are seen in a very wide variety
of neurological disorders, including Alzheimer's disease, Amyotrophic Lateral
Sclerosis and Parkinson's disease. The current focus of our research is
to better understand neurofilament structure, function and involvement
in disease processes.
Trainee Participation in this Research: A trainee could
expect to learn biochemical techniques for analysis, purification and characterization
of proteins. It is likely that immunological techniques such as the raising
of antibodies and their use immunohistochemically to map the distribution
of proteins of interest in tissues and in neuron cultures would also be
used. Molecular biological and computer-based techniques to elucidate primary
sequence, evolutionary and structural information will also be used when
appropriate. Finally, we occasionally perform electron microscopical analysis
of cells and biochemical preparations.
James W. Simpkins, Ph.D., Professor, Pharmacodynamics: The major
interest of my research program is the neuroendocrine regulation of reproduction
and related neuroendocrine processes. We use in vivo and in vitro neurons
in the regulation of reproductive processes. Normal physiology is evaluated
in young animals and age-related changes in neuroendocrine function are
examined over the life-course of animals. Particular interest is directed
at understanding the role of endogenous opioid peptides in the feedback
action of ovarian steroids on the brain. Additionally, we have undertaken
a major effort in determining the role of ovarian steroids in the normal
function of various brain neuronal systems with an emphasis on the role
of estrogen in cytoprotection and cognition.
Trainee Participation in this Research: Trainees use a variety
of techniques to address original hypotheses. These techniques include
(but are not limited to) radioimmunoassay of neuropeptides and hormones,
brain surgical techniques, behavioral assessment, assay of neurotransmitters
and related enzymes, receptor binding assays and molecular biology methods.
These techniques are applied to small animals and to in vitro cell
lines including primary cell cultures, neuroblastomas and gliomas.
Alan C. Spector, Ph.D., Assistant Professor, Psychology: My
research focuses on understanding how the mammalian nervous system organizes
and processes taste information. To accomplish this, we alter the flow
of ascending gustatory information by producing lesions in the central
nervous system and transecting various peripheral nerves in rats. A variety
of sophisticated behavioral techniques are employed to assess gustatory
function. A specially designed rodent taste-testing apparatus is used in
many of these experiments and serves as a "behavioral microscope". The
challenge is to ascribe a functional significance to the neural circuits
of the gustatory system. What parts of the circuit are necessary for the
animal to maintain discriminability among various classes of chemical stimuli?
To what degrees do the electrophysiological characteristics of gustatory
neurons correspond with the measured psychophysical characteristics of
the animal? What portions of the system are required for the significance
of gustatory signals to be modified by learning? To what extent is the
anatomical convergence of gustatory and visceral afferents reflected in
the functional integration of these signals. These are some basic questions
which we are trying to address in my laboratory.
Trainee Participation in this Research: In my laboratory
students learn basic psychobiological techniques including: electrolytic
lesion production, chemical lesion production (these include electrophysiological
guidance techniques), nerve surgery, perfusion, histological tissue preparation,
and histological analysis of brain and oral tissue. Students also learn
a variety of behavioral methodologies including the temporal analysis of
eating and drinking patterns, animal psychophysics, oral motor taste reactivity
procedures, and conditioned taste aversion methods. In addition, students
learn how to program and use computers to both operate instrumentation
and analyze data.
Donald J. Stehouwer, Ph.D., Associate Professor, Psychology:
The primary research focus of our laboratory is on neural remodeling during
normal development, and how that remodeling generates adaptive behavioral
development. We are using frogs to study the ways in which development
of central locomotor controls mediate the metamorphic transition from undulatory
swimming to appendicular locomotion. These studies include the study of
neural mechanisms of coordination, as well as the ways in which those mechanisms
interact with changing morphology, changing sensory input, and a changing
environmental niche to ensure harmonious maturation of coordinated behavior.
We have recently begun to conduct comparative studies development of appendicular
locomotion in different amphibia in order to better understand the phylogenetic
origins of vertebrate locomotor circuits. We are also conducting complementary
neural and behavioral studies of locomotion in rats.
Trainee Participation in this Research: A variety of neuroanatomical,
electrophysiological, pharmacological and behavioral techniques are brought
to bear on these problems. Anatomical techniques include routine histological
techniques, such as Nissl stains, myelin stains, and tract-tracing via
horseradish peroxidase and fluorescent labels. Electrophysiological techniques
include electromyography, population and unit recordings from nervous tissue
in vitro, and electrical stimulation of CNS tissue. Pharmacological techniques
include high performance liquid chromatography, injection of pharmacological
agents into intact animals, and electrophysiological assessment of pharmacological
agents in vitro. Behavioral techniques include time-lapse, slow motion,
and frame-by-frame video analyses. Behavioral data collected include measures
of gross motor activity, as well as fine-grain analyses of movements and
their coordination.
Wolfgang J. Streit, Ph.D., Associate Professor, Neuroscience:
The overall goal of this research is to develop an understanding of how
microglial act as specialized immune cells of the brain, and how their
functioning relates to the pathogenesis of CNS disease. Function
of microglia as immunocompetent cells of the CNS. Microglial immune functions
are being studied in a number of experimental pathological circumstances,
such as brain tumors, nerve lesions, and neural transplants. Aspects of
microglial activity being examined include the following: Anti-glioma defense
mechanisms and tumor cytotoxicity. Cytokine production and changes in immunophenotype.
Experimental in vivo modulation of cytokine production and immunophenotype.
Role in motor neuron regeneration. Role in initiation of brain inflammatory
diseases. Role in transplant rejection. Maintenance of the nervous tissue-blood
interface.
Colin Sumners, Ph.D., Professor, Physiology: The major
area of research in my laboratory concerns peptide receptors in the brain.
Specifically, we are interested in the regulation and cellular functions
of angiotensin II and atrial natriuretic peptide receptors in neurons and
glia derived from brain. In addition, we also investigate the altered expression
of these receptors in brain cells from hypertensive animals.
Trainee Participation in this Research: Methodologies include:
Primary brain cell culture; radioligand binding; analysis of intracellular
messengers (e.g. CAMP, CGMP, phosphoinositide hydrolysis, protein kinase
C); analysis of receptor proteins (Western Blots); analysis of mRNAs for
receptors.
Philip Teitelbaum, Ph.D., Graduate Research Professor, Psychology:
In collaboration with Dr. Ralph Maurer in the Department of Child Psychiatry,
we are developing a method for the computerized evaluation of the movement
and auditory synchronies involved in the foundation and maintenance of
emotional attachments. We use the Eshkol-Wachman movement notation system
for such analysis. We believe a fundamental disruption in such synchrony
exists in autistic children, and are beginning an experimental analysis
of this phenomenon in autistic and normal children.
Trainee Participation in this Research: Students working in my
laboratory receive comprehensive training in methods of analysis of behavior.
Floyd J. Thompson, Ph.D., Associate Professor, Neuroscience: We
are currently investigating cortical/brainstem modulation of segmental
motor mechanisms. In collaboration with Ronald Parmer, M.S., Charles
J. Vierck, Ph.D., and Prodip Bose, M.D. Ph.D. (Dept of Neuroscience) we
are investigating the neurophysiological and neuropharmacological mechanisms
that regulate sensory-motor function in the spinal cord and how these are
changed by spinal cord injury. In collaboration with Paul J. Reier, Ph.D.(Depts.
of Neurosurgery & Neuroscience), we are evaluating processes associated
with recovery of function, and in particular we are testing the potential
for enhanced functional recovery mediated by neural tissue transplantation
into the injured spinal cord in a laboratory model of spinal cord trauma.
In a project directed by Edward Wirth, M.D., Ph.D. (Dept. of Neuroscience),
co-investigators Paul J. Reier, Ph.D., Douglas K. Anderson, Ph.D.(Dept.
of Neuroscience), and Richard Fessler, M.D. (Dept. of Neurosurgery) we
are evaluating the safety and feasibility of intraspinal neural tissue
transplantation in patients with syringomyelia. These studies involve
evaluation of patients before and at quarterly intervals for two years
following the transplantation procedure. In this project, we are
collaborating with Basim Uthman, M.D. and Susan Mott, M.D. (Dept.
of Neurology), to analyse spinal cord and cortical evoked potentials. And
in collaboration with Andrea Berhman, Ph.D. and Mark Trimble, Ph.D. (Dept.
Of Physical Therapy), we are evaluating lower limb spasticity. Additional
projects include an evaluation of the neurophysiological basis for activity
directed neuroplasticity produced by specific locomotor training
in a laboratory model of spinal cord contusion trauma.
Trainee Participation in this Research: 1. We utilize neurophysiological
analysis of spinal reflex excitability as a basic tool, alone or combined
with stereotaxic procedures for microstimulation and recording from specific
brainstem nuclei. 2. In collaboration with Dr. Paul Reier's Laboratory,
we use spinal cord single unit analysis to investigate intraspinal transplant
neuron and host neuron interactions.
Edward Valenstein, Ph.D., Professor, Neurology: We have
been conducting studies in primates in two principal areas: (1) the behavioral
and anatomic definition of disorders of attention, in particular, multimodal
neglect and extinction. Behavioral tasks have been devised to distinguish
motor from sensory aspects of these attentional disorders. Investigation
of lesions that may cause neglect in the vertical rather than lateral dimension
are underway. (2) We have been studying the role of the retrosplenial cortex
in memory.
Trainee Participation in this Research: Students working in this
lab would learn methods of testing for sensory and motor capacities of
primates, and they could also participate in related investigations of
human patients with cortical injuries.
Carol Van Hartesveldt, Ph.D., Professor, Psychology: The
focus of research in this laboratory is the functional significance of
neurotransmitters in the basal ganglia. In adult animals, the behavioral
effects of hormones and agonists and antagonists of endogenous neurotransmitters
are tested by direct injection into the neostriatum and nucleus accumbens.
In developing animals, these same drugs are used to measure the functional
development of neurotransmitters systems in the basal ganglia, and to examine
the behavioral significance of the changing relationships between these
systems. A further focus is the pharmacological characterization and neuroanatomical
localization of L-DOPA-induced air-stepping, a phenomenon induced by L-DOPA
in developing animals. Determining the neural mechanisms underlying the
changing gaits and rate of stepping in this model will provide new insights
regarding the development of locomotion.
Trainee Participation in this Research: Students in this lab
will learn special techniques for designing and carrying out biobehavioral
research in preweanling rats. Experimental design techniques in developmental
studies include the split-litter technique, as well as providing appropriately
thermoneutral environments for pups at different ages. Pre-surgical techniques
include cold anesthesia and inhalation anesthesia as well as adapting the
stereotaxic instrument for use on animals with non-calcified skulls. Surgical
techniques include transection of the brain and spinal cord at various
levels; as well as implantation of indwelling cannulae in the brains of
developing rat pups. Students will prepare drugs for intracerebral injection
and carry out the injections. Behavioral measures to be learned include
videotape analysis as well as the use of automated activity monitors with
computerized data collection and analysis systems. Students will learn
to perfuse, section, and stain immature brains.
Thomas W. Vickroy, Ph.D., Associate Professor, Physiological Sciences:
The general research interests of this laboratory involve the neurochemical
and molecular bases for chemically-mediated synaptic transmission between
CNS neurons and their target cell populations. Specific interests include
understanding the functional roles of presynaptic autoreceptors that regulate
transmitter release, understanding the biochemical basis and functional
significance of interactions between co- localized neuroactive substance,
and delineating the role of reversible protein phosphorylation in stimulus-dependent
release of neurotransmitters. The overall aim of these investigations is
to obtain a more complete understanding of chemical neurotransmission and
to identify molecular targets for drugs which may reverse specific changes
brought about by certain cognitive and affective disorders.
Trainee Participation In this Research: Students involved with
these research projects are trained to utilize a variety of techniques
in order to gain a more thorough appreciation of the biochemical and molecular
bases for interneuronal communication. Students are trained to conduct
a variety of investigations in isolated tissue preparations, including
methods to investigate drug-receptor interactions, generation of intraneuronal
second-messenger molecules, and methods to assess the release of various
neuroactive compounds. In addition, they learn sterile surgical techniques
for intracranial implantation of microdialysis probes and associated techniques
to collect and analyze CNS extracellular fluid from awake freely-moving
rats for transmitters or other analytes of interest. All students learn
appropriate analytical methods in order to measure substances of interest,
including high-performance liquid chromatography with electrochemical or
fluorescent detection methods and procedures to isolate and identify neuronal
phosphoproteins.
Charles J. Vierck, Ph.D., Professor, Neuroscience: The research
interests of this laboratory involve the neural coding of somatosensory
input, with emphasis on correlation of behavioral, anatomical and physiological
studies. Micro-electrode and psychophysical studies in monkeys are concerned
with the functional significance of different pathways of somatosensory
conduction in the central nervous system. A strong emphasis on factors
that influence recovery of function after neural injury includes investigations
of the effects of spinal grafts of fetal tissue. Investigations of the
neural mechanisms of pain coding and inhibition are aimed at determining
effective methods of pain control. These include psychophysical evaluations
of human pain patients. Studies of touch, proprioception and motor abilities
are concerned with mechanisms of neural coding and reorganization. Investigations
of spinal reflexes are addressed toward an understanding of the causes
of spasticity and an evaluation of treatments.
Trainee Participation in this Research: Students are trained
to utilize a variety of techniques to understand mechanisms for coding
or modulation or plasticity of sensory and/or motor capacities. In all
cases, this involves the design and implementation of behavioral tests
for laboratory animals (primates, cats or rats) or humans. They learn to
adapt and train the subjects, to program behavioral contingencies and acquire
multiple channels of data, involving digital and analog signals representing
behavioral and physiological events. They learn sterile surgical techniques
for spinal cord and brain, including techniques of neural transplantation.
In different experiments, the laboratory utilizes acute, single unit recordings
or chronic recordings of EMG activity or evoked potentials. All students
learn anatomical procedures for reconstruction of lesions and grafts, and
most students are involved in anatomical investigations using immunocytochemistry.
Don W. Walker, Ph.D., Professor, Neuroscience: Our lab
is involved in a multidisciplinary investigation of the alterations in
neuronal structure, circuitry, function and plasticity associated with
chronic ethanol ingestion and aging. The rodent hippocampus is used as
a model neuronal system for investigating these questions with quantitative
neuroanatomical and electrophysiological techniques. Ethanol and/or aging-induced
neuroanatomical alterations are studied with computer-assisted analysis
of material prepared with a variety of histochemical procedures including
autoradiography, HRP, immuno-procedures and Golgi impregnation. Alterations
in synaptic distribution, synaptic response strength and synaptic plasticity
are studied using neurophysiological and pharmacological approaches including
single unit, extracellular field potentials, current source density analysis
and iontophoresis. In vitro hippocampal slices are used in these
studies. In collaboration with Dr. Heaton's lab, we are currently investigating
the hypothesis that the ethanol-induced structural/functional abnormalities
in the rat septohippocampal system may be at least partially mediated by
a suppression of neurotrophic influences by ethanol. Primary cell culture,
immunocytochemical, gene expression, and quantitative morphological techniques
are used to test this hypothesis.
Trainee Participation in this Research: Trainees working
in this laboratory will be able to learn a variety of techniques that are
being used to investigate the mechanisms of ethanol neurotoxicity. This
lab uses an interdisciplinary approach to this problem including the use
of neuronal cultures, immunocytochemistry, quantitative morphology. Northern
blot and in situ hybridization measurement of gene expression and measurement
of changes in cellular calcium flux.
Keith D. White, Ph.D., Associate Professor, Psychology:
There are two main projects currently underway. One project concerns the
molecular genetic basis of human color vision and heritable color vision
defects. In this study the color matching, luminance additivity, and light-exchange
thresholds of subjects are measured psychophysically to establish their
color vision phenotypes. DNA from the same subjects is analyzed by our
collaborators to reveal gene copy number and, in selected cases, the complete
amino acid sequences in their genotypes. The aim is clarify the linkages
between genotype and phenotype in color vision, a relatively common form
of normal genetic variation. The second project deals with visual-vestibular
interactions in the context of a computer-generated "virtual environment".
It explores the conditions which may lead to disorientation or motion sickness
when viewing a large moving stimulus which is enslaved to eye or head movements
made by a subject. Such symptoms are problematic in military flight simulators
and NASA teleoperation controllers.
Trainee Participation in this Research: Students working with
Dr. White learn sophisticated methods for testing visual and vestibular
functions and interactions.
Charles G. Widmer, D.D.S., M.S., Associate Professor, Oral and Maxillofacial
Surgery: The main focus of research conducted in this laboratory is
the study of motor control mechanisms for orofacial muscles using a combination
of anatomical, physiological and behavioral techniques. The scope of these
studies is to determine normal motor organization and control mechanisms
for various cranial muscles systems and how they may be affected by facial
pain conditions in laboratory animals and human subjects. The investigations
range from developmental issues regarding spatial and temporal organization
of central nervous system sensory and motor connections, anatomical partitioning,
and neuromuscular compartmentalization to mature form and function and
the effects of aging on these systems.
Trainee Participation in this Research: Students are trained
in anatomical methods including florescent labeling and 3D reconstruction
microscopy and image analysis techniques, neurophysiological methods such
as multichannel data acquisition and analyses of single motor unit data
or surface EMG data and EEG evoked potentials, extracellular recording
techniques in the brainstem and acquisition and analyses of force measures.
Students also learn laboratory animal and human subject protocols necessary
to conduct these experiments.
Edward D. Wirth, III, M.D., Ph.D., Research Assistant Professor,
Department of Neuroscience: Several cellular grafting approaches
have shown considerable promise for achieving at least partial anatomical
and functional repair of the injured spinal cord in animals. Even
though much basic science work must still be done to fully characterize
the ultimate therapeutic potential of these transplants, sufficient data
currently exists to begin limited, but rigorous, studies of these grafts
in human subjects. We anticipate that these initial clinical experiments
will provide valuable feedback to ongoing animal investigations and will
help establish an appropriate template for future large-scale clinical
trials of intraspinal grafting. Accordingly, one major focus in our
laboratory is an ongoing pilot clinical study that is testing the feasibility
and safety of human embryonic neural tissue allografts in patients with
posttraumatic syringomyelia.
Since spinal cord transplants cannot be biopsied
safely like other organs, a critical link in this bench-to-bedside transition
is the set of noninvasive diagnostic tools that enable us to assess the
viability of these grafts and their impact on the host spinal cord in living
subjects. Therefore, our laboratory is conducting magnetic resonance
imaging (MRI) and in vivo localized spectroscopy (MRS) studies of spinal
cord injury (SCI) and repair via cellular grafting methods. These
experiments are evaluating : (1) the relationship between MRI/MRS data
and the degree of neurological impairment following SCI, (2) the application
of advanced MRI techniques such as diffusion-weighted MRI and diffusion
tensor mapping to provide detailed information on the degree of white matter
sparing following SCI, and (3) noninvasive detection of neural tissue transplant
rejection by MRI/MRS. Additional areas of interest include: functional
MRI of the spinal cord, development of implanted radiofrequency coils for
in vivo high-resolution MRI and localized MRS of spinal cord injury and
transplants, and translation of preclinical MR research to the clinical
arena.
Trainee Participation in this Research: Trainees in this laboratory
will have the opportunity to be involved both basic and clinical research
on SCI and neural tissue grafting. These studies will require each
trainee to master a wide range of research skills, including: neural tissue
microdissection, spinal cord injury and transplantation surgery, magnetic
resonance imaging and spectroscopy, clinical assessment of neurological
impairment in animals and human SCI patients, morphometric analyses, and
biostatistics.
THE CENTER FOR NEUROBIOLOGICAL SCIENCES
ADMINISTRATIVE BOARD:
Dr. Robert Sorenson, Provost
Dr. Donald Price, Vice President of Graduate Studies and Research
Dr. Alan Neims, Dean, College of Medicine
Dr. William Harrison, Dean, College of Arts and Sciences
DIRECTORS:
Dr. Charles J. Vierck, Professor, Department of Neuroscience
Dr. Carol Van Hartesveldt, Professor, Department of Psychology
PURPOSE:
The Center for Neurobiological Sciences (CNS) coordinates, encourages
and supports interdisciplinary research on the nervous system at the University
of Florida. The Center provides stipends, through a training grant from
the National Institutes of Mental Health, to students whose advisors are
members of the Center. These stipends are intended to encourage the investigation
of brain-behavior relationships. We provide a variety of educational programs
for all students and faculty with an interest in the neurobiological sciences.
The Center sponsors a local neuroscience meeting in the fall and a regional
neuroscience meeting in the spring. We bring in a number of outstanding
speakers for seminars throughout the year, and travel support is provided
for students and faculty to attend meetings and present their work or to
acquire new technical skills. The Center supplements departmental offerings
with several formal courses in the neurobiological sciences, and forums
are provided for students to gain experience with oral and written presentations
of their scientific interests. The Center does not admit students into
formal degree programs; these are offered by Departments of the University.
The purpose of the Center is to enhance these departmental programs by
providing broad perspectives and interdisciplinary research experiences
in the Neurobiological Sciences.
BACKGROUND:
The origins of our present cross-departmental research training program
go back to 1957, when training efforts were informally coordinated between
the Departments of Anatomy, Psychology and Neurosurgery. At that time the
College of Medicine had been in existence for one year. This early interaction
provided a program of study in nervous system for graduate students in
Physiological Psychology and Anatomy, giving them anatomical, physiological
and behavioral skills for neurobiological research. As Neuroscientists
joined the faculty of different departments with evolving graduate programs,
it became desirable to formalize an administrative structure to oversee
interdisciplinary training in the Neurobehavioral Sciences. The University
responded by officially establishing the Center for Neurobiological Sciences
as the first University-wide organization for cross-departmental interaction.
This was a pioneering venture for the University, in response to creative
faculty members who anticipated the direction in which Neuroscience training
must go. The formal establishment of the Center for Neurobiological Sciences
greatly facilitated acquisition of training grant support from NIMH, which
has been in effect since 1965.
COMPOSITION AND ADMINISTRATION:
The Administrative Board appoints the directors of the Center. The present
co-directors have been members of the Center since 1965 (CJV) and 1970
(CVH) and have directed the Center's activities since 1978. The directors
represent the Health Center complex (CJV) and the main campus (CVH). The
number of faculty members has grown from the original 6 members to 46.
There are 48 faculty associates of the Center, and an additional 56 faculty
at the University with interests in neurobiology receive notice of the
seminars and other activities of the Center. In addition to 7 students
who receive fellowships from the training grant, 45 students participate
in our training functions and therefore are considered as Center trainees.
All of the day-to-day operations of the Center include the participation
of one or both directors, but none of these activities are dictated by
either of us. We sit on each of the Center's committees, and all functions
are directed by a committee or decided by a vote of the entire membership.
The overall direction of the Center's program is discussed and conceived
by the STEERING COMMITTEE, comprised of members who have been especially
active and responsible toward Center activities (currently Drs. Vierck,
Van Hartesveldt, Leonard, Reier and Stehouwer). Recommendations of the
steering committee are then transmitted to other committees; every aspect
of the Center's operation is conducted by a democratic process that involves
a cross-section of the members or all the members.
The MEMBERSHIP COMMITTEE (currently Drs. Vierck, Van Hartesveldt, Fregly,
W. Dawson, Simpkins, Walker and Leonard) receives suggestions for new members
from the entire membership. Associates of the Center are appointed directly
by the committee and are then invited by the directors and notified of
the purposes and activities of the Center and of the criteria for becoming
a full member. The category of associate member is designed to include
an individual in all Center functions, to give him or her the opportunity
to become active in the Center and to meet the Center faculty. New tenure-track
faculty with an interest in Neurobiology are offered Associate membership.
Postdoctoral fellows and assistant research scientists who are working
with Center faculty are also appointed as associate members. Postdocs remain
associates during their fellowships, but research scientists can become
full members.
Associates are nominated to become full Members if the committee feels
that the person: 1) is conducting a quality research program, 2) has actively
participated in the programs of the Center and 3) is genuinely interested
in interdisciplinary collaboration and training of students. Following
a successful review by the membership committee, each nominee is invited
to submit a curriculum vitae for review and voting by the members. Because
the committee conservatively nominates excellent candidates for membership,
it is rare that a nominee is not voted in, once a vitae is submitted, but
the process of reviewing and voting further familiarizes the faculty with
the new member. Members of the Center are eligible to sponsor student applications
for Center fellowships, and they are given preferential access to Center
funds for travel and for sponsorship of outside speakers or visiting scientists.
Members of the CNS have their primary appointments within a number of
departments at the University. These include: Anatomy, Physiology, Pharmacology,
Neurology, Neurosurgery and Ophthalmology (in the College of Medicine),
Oral Biology (In the College of Dentistry), Physiological Sciences (in
the College of Veterinary Medicine), Pharmacodynamics (in the College of
Pharmacy) and Psychology and Zoology (in the College of Arts and Sciences).
Given this wide distribution of talent across the campus, the Center continues
as an important vehicle for communications which lead to productive working
relationships among students and faculty who are predisposed toward collaborative
efforts.
The FELLOWSHIP COMMITTEE reviews applications by students and awards
the stipends provided by the training grant. The members of this committee
(currently Drs. Vierck, Van Hartesveldt, Heaton [chair], Berg, Hunter,
Luttge, Thompson, Raizada, Stehouwer) represent each department that awards
graduate degrees. The committee meets once yearly, after the students of
Center Members are notified of the opportunity to apply for training grant
stipends. Each member of the committee rates the students according to
specified criteria, given information that is provided by the student on
application forms. Each applicant is evaluated on the basis of: 1) their
academic record, 2) accomplishments in the laboratory and their research
plans, 3) fulfillment of Center requirements (the Medical Neuroscience
and Behavioral Neuroscience courses and submission of an individual predoctoral
application), 4) the behavioral relevance and interdisciplinary nature
of their research, 5) their attendance and participation in Center activities
and 6) a letter of recommendation by their advisor. Stipends are awarded
only to students who have demonstrated their abilities in coursework and
the laboratory - usually after 2 or 3 years of graduate training.
For administrative purposes, several categories of Center students are
identified. In the fall of each year, the graduate advisors of the departments
affiliated with the Center are requested to send us a list of new students
with an interest in Neurobiology. These Student Associates are placed on
our mailing list and are notified of all Center functions. The list of
student associates is revised yearly, on the basis of attendance and interest
in the programs of the Center. Because it is not appropriate for all of
the students with excellent records to receive stipends from the training
grant (e.g., because they have secured other funding or are ineligible
as foreign students), any student who applies to the Fellowship Committee
and is favorably reviewed is listed as a Center Trainee. All Center trainees
must meet the requirements for receipt of a Center Fellowship. Trainees
have preferential access to Center support of travel, for sponsorship of
Center speakers or visiting scientists and for supplies to assist their
dissertation research.
The ACTIVITIES COMMITTEE (currently Drs. Vierck, Van Hartesveldt, P.
Anderson, R. Dawson, E. Meyer, Reep, Reier, Shaw, Sumners and Zengel) plans
the program for each year and divides the responsibilities for organizing
each function. The committee meets in the summer and fall of each year
to plan and organize the programs in response to written suggestions from
the members and students. The committee decides upon and schedules the
major functions for the year, and volunteers from the committee organize
each of these functions. The suggestions for individual seminars and visiting
scientists are discussed; a list of speakers is generated, and sponsors
for each visitor are identified.
PROGRAMS:
The programs of the Center are oriented toward training but are designed
to educate and facilitate interactions of both faculty and students. All
students that are affiliated with the Center receive their degrees in established
departments within the University, and the bulk of their course requirements
are determined by those departments. In addition, the Center provides a
broadly-based program of interdisciplinary training in the neural sciences
that takes advantage of direct input from many of the Center faculty members.
This, of course, is the mission of the Center - expansion of the resources
for training well beyond the confines of any single department. Because
each department represented in the Center presents a core curriculum, and
because our goal is to enhance research capabilities, much of our program
involves activities other than didactic courses. We do present several
courses (vide infra), and we require that certain other courses be taken
by Center Trainees (vide supra), but otherwise we fill important gaps in
the departmental curricula.
An important skill that receives too little attention in the standard
curricula is the ability to orally present research findings and handle
questions on the topic presented. Accordingly, we provide a variety of
opportunities for Center students to speak before a critical audience.
Neuroscience Nights. Each summer, all Center trainees and prospective
trainees give a research presentation (20 min.) that is followed by a 20
min discussion. These are evening sessions, involving only 2 or 3 presentations,
and refreshments are provided. The atmosphere is informal, and attendance
is high by both students and faculty. Even if a student has not yet gathered
sufficient data for a presentation, he or she outlines a research plan
and rationale. The format of these sessions requires that the students
organize their thoughts carefully and present the most important concepts
or interpretations succinctly.
Little Society for Neuroscience. Each student and faculty member of
the Center that submits an abstract for the Society for Neuroscience meetings
presents their poster or talk locally, one week before the national meeting.
Our local meeting requires at least half a day. Refreshments are provided,
and the recent emphasis on poster presentations provides ample opportunity
for in-depth discussions.
Nerve Net Meeting. Each year, the Center co-sponsors a regional Neuroscience
meeting under the auspices of the North Florida Chapter of the Society
for Neuroscience. The North Florida Chapter was formed by the CNS and the
Neurobiology program at Florida State University. Membership in the chapter
is defined by attendance at the South-East Nerve Net meeting (SENN), and
therefore includes individuals from other Universities (and states) in
the southeast. The meeting was initiated by the Whitney laboratory and
was held there from 1983 to 1987 (organized by Dr. Peter Anderson). Hosting
of the meeting now rotates between the Whitney lab (at Marineland), FSU
(in Tallahassee) and UF (held in Cedar Key). This two-day meeting emphasizes
student presentations and includes both slide talks and poster sessions.
The Center provides travel expenses for the students and for a keynote
speaker from outside the north Florida region.
Apres Neuroscience. Each year, following the fall meeting of the Society
for Neuroscience, the students and faculty that attended the meeting get
together for an informal discussion. Each person gives a short overview
of the poster or talk that most impressed them.
Another crucial skill that requires extra attention is scientific writing.
Although the Center cannot impose upon the students' time with a variety
of requirements for written reports, we do provide several important vehicles
for training of writing skills.
Grant Writing Course. At the end of their first or second year, Center
Student Associates take a 1-hour course that prepares them to write an
individual predoctoral application. In a seminar format, the processes
of submitting and reviewing grants are outlined by the co-directors, who
have been members of NIMH and NINCDS fellowship and research review committees.
The students write reviews of predoctoral proposals that have been submitted
in previous years, and they conduct a mock study section meeting for evaluation
of these proposals. The students begin writing their own proposals for
submission the following semester (for an additional 1 hour of credit).
The purpose of this course is to provide structure, incentive and assistance
for the students to define their research goals in writing at an early
stage of their graduate education. The fellowship application provides
a basis for a dissertation prospectus that is submitted later to the dissertation
committee. The students develop practical writing skills with optimal input
and feedback: they critically evaluate other proposals before writing their
own; their proposal is edited by their advisor; they receive feedback from
the NIMH review panel; and then they revise and hone the proposal for their
dissertation committee.
Efforts to expand the research experiences of students beyond the confines
of a single laboratory and department involve a variety of programs and
activities that: 1) provide frequent opportunities for communication with
UF faculty and students they would not otherwise be exposed to, 2) offer
similar exposure to visitors from outside the University and 3) provide
direct counseling of students on their dissertation project by experts
from outside the University.
The Center Seminar Series. We feel strongly that the students need to
observe the ways in which successful scientists approach their work and
articulate their results,and we accomplish this in a number of ways. We
provide a stellar list of talks by well-chosen experts. Each visit is hosted
by the laboratory that suggested the speaker, and the students are included
in the process of organizing and entertaining the speaker. The visit includes
several social events that are attended by students and faculty with an
interest in the topic or techniques presented by the speaker.
Regional Meeting and interchange. The Southeast Nerve Net Meeting has
been described above. This informal meeting away from the campus provides
the optimum environment for faculty and students to discover and discuss
mutual interests. Also, to maintain communications with our colleagues
on the east and west coast of Florida, we have an exchange program of speakers
for seminars and graduate courses. These efforts have led to collaborative
research projects and to membership by Whitney lab and FSU faculty on the
dissertation committees of Center students.
Journal Clubs. As a natural outgrowth of the influences of the Center,
a variety of journal clubs have formed, to meet the needs of the students
and faculty for active discussions of current research in their area of
interest. The topics come and go from year to year, and they have been
organized both by faculty and students. Currently active journal clubs
are on: "The Spinal Cord", "Sensory Systems", "Developmental Genetics"
and "General Neuroscience".
The Visiting Scientist Program. When requested by a student or faculty
Member, a visitor is supported by the Center to introduce a new technique
or otherwise assist with the conduct of a research project. The visits
take a variety of forms, ranging from demonstrations or workshops that
are attended by a group of students, to participation in experiments in
a member's laboratory, to consulting on the research plan (e.g., on a dissertation
committee) or assisting with theoretical modeling.
Travel to Meetings or Laboratories. Often a student or faculty Member
will benefit more from travel to another laboratory or to a short course
than from a consultation by a visiting scientist. Center support of this
type of travel has assisted greatly in bringing new expertise or research
directions to our Members. Also, the advanced students need experience
with presenting their work and need exposure to the scientific community,
and money for this purpose is often not available on research grants.
DISCLAIMER