Essel Program - 2004 Annual Report
The Neuroscience Program The Neuroscience Program has continued to thrive in the past year. Sixty-eight students enrolled in Introduction to Neuroscience and there were sixteen seniors who graduated with a concentration in Neuroscience. Additionally fifteen students worked in neuroscience professor's laboratories over the summer and seven completed honors theses. I.
Undergraduate Research Fellows: II. Williams Neuroscience Faculty: The
faculty was actively engaged in research and teaching this past year.
Faculty publications that were supported in part by Essel funds are listed
in Appendix III and a summary of all of their work in addition to publications
can be found in Appendix IV. Appendix V enumerates all other current sources
of funding for Neuroscience faculty and the corresponding project. III. Neuroscience Courses: This
year in the Introduction to Neuroscience course (NSCI 201) we maintained
the expanded laboratory component from the previous year, continuing with
five labs and a lab report, as opposed to the four labs of previous years. IV. Essel Fellow: Dr.
Luis Schettino continued to do an excellent job as the instructor of the
Introduction to Neuroscience class labs during his second year as the
Senior Essel Fellow, and accomplished a number of other things as well.
This winter study period, he taught a very popular winter study course
entitled The Neuropsychological Basis of Creativity. He also took on a
student researcher for the summer and continued pursuing his research
interests on the neural basis of sensorimotor controls using the EEG/ERP
(electroencephalo-graphy/event-related potentials) equipment he set up.
Throughout the year he conducted a human evoked potential experiment designed
to explore the timing of cortical activation during the perception of
graspable objects as compared to non-graspable ones. Two of his research
efforts were published this year, one in Experimental Brain Research and
the other in Neuropsychologia (see APPENDIX III). He is also preparing
an article for publication on the motor deficits of Parkinson's disease
patients during grasping. V. Colloquium Speakers: The Neuroscience program had continued success in bringing interesting and qualified speakers to campus this year. A listing of these speakers and their topics and affiliations can be found in Appendix VI. VI. Williams College Program for Undergraduates at the Marine Biological Laboratory at Woods Hole: Dr. Steve Zottoli continued to direct the Williams College Program for undergraduate studies at the MBL. Additional funding for the program was provided by Howard Hughes Medical Institute and Nan and Howard Schow. A summary of the student's activities can be found in Appendix IX. VII. Budget: Appendix VII presents the expenditures for year 11. An explanation of expenditures is also provided in that appendix. cc:
W. Lenhart, Dean of the Faculty APPENDIX I: 2003 ESSEL NEUROSCIENCE FELLOWS
Student: Nicolas Bamat ('04)
Student: Miles Belknap ('05)
Student: Gregory Del Prete ('04)
Student: Rosemary Eseh ('04)
Student: Alyssa Fluty ('05)
Student: Tory Hendry ('04)
Student: Peter Holland ('05) Student:
Maria Kerr ('05)
Student: Michelle Kron ('04)
Student: Rui Nie ('05)
Student: Kristin Sageser ('04)
Student:Kameron Shahid ('04)
Student: John Rudoy ('05) Student:
Molly Wasserman ('04) Student:
Meredith Olson APPENDIX II: ABSTRACTS OF NEUROSCIENCE HONORS THESIS Dose-dependent Effects of Estradiol on Learning Following 4-vessel Occlusion Nicolas
Bamat Ischemic events such as cardiac arrest and stroke affect over a million people in the United States every year. Cognitive deficits following such events are often associated with damage to the hippocampus. Using animal and cell culture models, estradiol administration has been shown to protect the hippocampus from such damage. Furthermore, in male rats it has been shown in that estrogen-mediated neuroprotection from ischemic injury can be demonstrated in behavioral models of learning and memory dependent on the hippocampus. The present study examined whether this behavioral neuroprotection is dependent on sex or the level of estradiol using a 2 (Sex: Male and Female) x 3 (Hormone: Placebo, Low Estradiol (.25mg/pellet), High Estradiol (2.5mg/pellet)) x 2 (Surgery: Ischemia and Sham) design. Gonadectomized male and female rats were implanted with 21-day time-release hormone pellets on PND 35 and experienced transient global ischemia via four-vessel occlusion or a sham surgery two weeks later. A week following surgical procedures, all rats were tested on a non-hippocampally dependent visible platform Morris Water Maze (MWM) variant and then on the hippocampally dependent hidden platform MWM. Blood samples were obtained via cardiac puncture to determine plasma estradiol levels on the day of ischemia. Estradiol levels were quantified using radioimmunoassay (RIA). No sex differences were observed in either the visible or the hidden platform tasks. Subjects treated with high estradiol performed significantly worse than those pretreated with placebo capsules on the visible platform task. Sham subjects receiving high estradiol performed significantly worse than subjects receiving low estradiol on the MWM. However, this result was reversed in ischemic subjects, with high estradiol subjects outperforming subjects from the low estradiol group. These findings suggest a differential dose-dependent response in performance on the MWM in ischemic and non-ischemic animals. The Effect of Nerve Damage on Song Representation in the adult Zebrafinch Brain Gregory
Del Prete As closed-ended learners, male zebra finches normally go through one song learning process, which concludes with song crystallization at about 90 days of age. Thereafter, the bird will sing only this crystallized song unless some form of outside intervention induces song plasticity. The closed-ended song learning process results in a representation of a bird’s own individual song in the high vocal center (HVC) and other song production nuclei in the brain. Thus, a recording of a bird’s own song will illicit a more robust response from auditory response neurons within HVC than will any other sound stimuli. The bird will reenter a period of song plasticity and crystallized song will change, however, if one half of the bird’s vocal organ, the syrinx, is uncoupled from the brain. A region of the brain that is normally required for proper song learning, but not necessary for adult song production, LMAN, must be intact in order for this nerve-damage-induced plasticity to occur. This suggests that song plasticity corresponds with plasticity in the brain itself. In this study, the right half of the syrinx was denervated in adult male zebra finches, causing the subjects to alter their crystallized songs. Recordings of each subject’s own song before and after nerve injury were presented to each bird after song recrystallized. In none of the six subjects studied did HVC respond most strongly to intact, crystallized song. All six birds showed the greatest HVC response for one of their own songs recorded after nerve damage, and five of the six subjects showed increased responses to songs that contained new features not seen in original song. These results suggest that, under certain circumstances, brain plasticity is possible in male zebra finches during a phase of life when this normally would not be the case. Identified Neuron Activity in a Freely Moving Crayfish Shauna
Dineen The
posture of the crayfish abdomen is regulated by the antagonistic action
of the flexor and extensor muscles. Muscle movements are controlled by
premotor interneurons that coordinate firing activity in the motor neurons
innervating these muscles. The nerve innervating the superficial flexors
contains the axons of the 6 motor neurons - 5 excitatory (SFMN1-4,6) and
1 inhibitory (SFMN5). Although previous studies based on interneuron stimulation
have suggested that the 5 excitatory neurons will fire during abdominal
flexion and the 1 inhibitory neuron will fire during extension, no study
has yet correlated individual neuron activity with behavior in a freely
moving crayfish (Procambarus clarkii).
Rosemary
Eseh Studies on the behavioral effects of iron deficiency (ID) have focused on the postnatal or adult periods. In addition, little attention has been paid to ID effects on affective behavior although alterations in the relevant neurotransmitter system, GABA, have been documented. In this experiment, two measures of anxiety, ultrasonic vocalizations (USV) and elevated plus maze (EPM) were used to investigate the consequences of maternal ID. Female Long-Evans rats were assigned randomly to one of three diet groups: low iron (10-20ppm Fe), standard (60ppm Fe) or lab chow (250ppm Fe) diet. Diets started seven days prior to mating and continued until ten days after birth (PN10), after which all dams were iron replete with the lab chow diet. USVs after maternal separation was used to test for anxiety in neonates and EPM was used for adults. Maternal behavior, growth, and activity were also assessed. Blood samples taken from pups on PN10 revealed a significant decrement in serum iron and a compensatory increase in total iron binding capacity in the low iron groups compared to the control groups. Relative to the two control groups, the low iron group weighed less on PN1, and this weight difference persisted in adulthood. In neonates, the rate of USVs in the low iron group was significantly higher than the two control groups, and their general activity was significantly less than the controls’. Maternal behavior was not significantly different across groups. By adulthood, anxiety behavior and motor activity in the low iron group were comparable to controls. This study shows that prenatal deficiency results in anxiety behavior, low weight and decreased activity. These deficits, except for weight, were reversed with iron repletion. Future research is needed to elucidate the mechanism of ID effects on anxiety and the persistent weight deficit. Microsatellite Isolation from the House Finch (Carpodacus mexicanus): A Protocol for Implementing Microsatellite Markers in the Study of Cultural Evolution. Tory
Hendry In order to develop a molecular marker based protocol for the study of song dialects and cultural evolution we attempted to isolate microsatellite loci from the house finch, Carpodacus mexicanus. We tested a new procedure for this isolation, involving multiple microsatellite enrichment methods and the use of the non-palindromic restriction enzyme BseYI to create unique sticky ends. This procedure was not successful, as we were not able to isolate any new loci, and it showed little promise for future work. We also tested both microsatellite and non-microsatellite genetic markers on a sample of birds from two different dialect regions to determine their relatedness and found that these two types of markers did not behave similarly. Using microsatellite loci we were able to determine that differences in song pattern do not serve as a barrier to interbreeding between neighboring populations in this species. We also found intriguing evidence that eastern house finch populations may be lacking in genetic diversity and genetically divergent on a macrogeographic scale. HsP27 is Required for Neural Development in the Zebrafish. Courtney
Juliano Heat
shock proteins (HSP’s) are highly conserved proteins whose expression
is induced in response to heat shock. They act as molecular chaperones
by helping to fold or re-fold proteins after a thermal event and by targeting
misfolded proteins to degradative machinery within the cell. One particular
HSP that is highly conserved in vertebrates is the small HSP27. This protein
functions in neuronal and non-neuronal differentiation, conveying resistance
to apoptosis, and providing protection against oxidative stress.
Dibutytyl-cAMP
Effects Spinal Cord Regeneration in the Michelle
Kron A
spinal cord crush at the spino-medullary level results in the loss of
function below the wound in goldfish, Carassius auratus. Miraculously
these animals recover swimming, feeding, equilibrium and startle responses
a few months after injury (Zottoli and Freemer, 2003). However, not all
central neurons (i.e. nerve cells confined to the central nervous system)
contribute to this behavioral recovery. For example, a pair of identifiable
nerve cells, the Mauthner cells (M-cells), morphologically regenerate
after injury but the growth follows aberrant pathways and ultimately does
not contribute to the recovery of startle responses that it is known to
initiate in normal fish. Effects of Early Isolation-Induced Stress on Play Behavior and Vocalizations in Rats. Kristin
Sageser Early childhood deprivation is associated with an increased risk of attachment and other social behaviors. The consequences of exposure to early stress in rodents have been used to model the effects of child neglect in humans. In this thesis, we examined the effects of early stress on the development of play and communicative behaviors. We first compared the model of early stress used in this laboratory (Early Deprivation, ED), in which pups are isolated individually on PN2-14 while the dam is left with a subset of littermates in the nest, to the Maternal Separation (MS) model, in which the dam is isolated in a novel cage while the pups are separated together. Undisturbed, control litters were used as well. We hypothesized that both models would cause subsequent alterations in play behavior and vocalizations at one month of age, but that these effects may differ due to the accentuated maternal factors in the MS model. Maternal behavior upon reunion with the isolated subjects was significantly increased in the MS condition, and less dramatically increased in the ED condition. ED experience significantly increased levels of play in behaviors such as attacking, boxing, and evading. Maternal Separation also significantly increased levels of play in measures such as attacking and evading, but these behaviors were significantly less than ED levels. Minor alteration were also seen in vocalizations as a result of ED experience. Since we found effects of a two-week separation in Experiment 1, in Experiment 2, we looked to see if there was a critical period of neural development responsible for these changes by confining the separation experience to either the first or second week. Separation during Week 1 produced increased levels of play that exceeded elevations resulting from two-week separation to Week 1 and two-week separations. These results indicate that the early stress affected play behavior and vocalizations, but these effects varied with the paradigm of timing and separation.
APPENDIX III: ESSEL SUPPORTED PUBLICATIONS AND PRESENTATIONS * indicates student author Lara Hutson Publications Invited
talks Presentations
Publications Presentations Sandstrom, NJ & *O’Brien, JL (October, 2003). Pretreatment with 17?-estradiol, but not 17?-estradiol, protects against global ischemia-induced spatial learning deficits in male rats. Society for Neuroscience, New Orleans, LA. Luis Schettino Publications Schettino, L. F., Rajaraman, V., Jack, D., Adamovich, S. V., Sage, J. and Poizner, H (2004). Deficits in Hand Preshaping in Parkinson’s Disease. Neuropsychologia, 42: 82-94. Paul Solomon Publications Solomon, P.R. & DeVeaux, R. (2003). "Gingko and Memory." Journal of the American Medical Association, 289 (5): 546-548. Solomon, P.R. (2003). "Repeated MMSE: A screening instrument for Alzheimer's Disease." Journal Watch Neurology, 5 (5):35. Murphy, C.A., Solomon, T.M., *Im, A., *Stashwick, C. & Solomon, P.R. (2003) "Is Alzheimer's Disease being diagnosed earlier: A 10-year retrospective study." International Psychogeriatrics, 15 (supplement 2): 89. Solomon, P.R., Ruiz, M.A., & Murphy, C.A. (2003). "The Alzheimer's Disease Caregiver Questionnaire: Initial Validation of a Screening Instrument." International Psychogeriatrics, 15 (supplement 2): 87. Budson,
A.E., Simons, J.S., Sullivan, A.L., Beier, J.S., Solomon, P.R., Scinto,
L.F., Daffner, K.R., & Schacter, D.L. (2004). "Memory and emotions
for the 9/11/01 terrorist attacks in patients with Alzheimer's disease,
mild cognitive impairment, and healthy older adults." Neuropsychology,
18: 315-327. Tolar,
M., Cassella, J., Villalobos, A., Bednar, M., Weaver, J., Davidson, W.,
Gibbs, M, Weiner, M., Solomon, P.R. (2004). "GABA A receptor inverse
agonist fails to improve cognition in Alzheimer's disease patients."
Neurology, 122: 315. Heather Williams Publications Invited
talks Steve Zottoli Publications Zottoli, S.J. and Freemer, M.M. (2003). Recovery of C-starts, equilibrium and targeted feeding after whole spinal cord crush in the adult goldfish, (Carassius auratus). Exp Biol., 206:3015-3029. Invited
talks
Publications Invited
Talks "Development: Experience Counts." REU Program in Neuroscience, SUNY-Albany, Albany, NY. July, 2003. "Neurosteroids and the development of sex differences in anxiety behaviors." The 5th Pharmacology Biochemistry and Behavior Meeting, Morzine, France. January, 2004. Research
Presentations Zimmerberg, B., *Sageser, K.E. (2003, Nov) "Comparison of early stress models on subsequent alterations in social and communicative behavior in rats." Presented at the International Society for Developmental Psychobiology annual meeting, New Orleans, LA. *Bamat,
NA, *Kron, M.M., *Schulte, A., Brunelli, S.A. and Zimmerberg, B. (2003,
Nov). Acute and long-term behavioral effects of toluene in neonatal rats
selectively bred for high or low vocalizations. Presented at the Society
for Neuroscience annual meeting, New Orleans, LA. APPENDIX IV: NEUROSCIENCE FACULTY ACCOMPLISHMENTS Professor Professor Lara Hutson In this, her first year at Williams, Dr. Hutson taught two new courses, Cell Dynamics (BIOL 410) in the fall and Mechanisms of Nervous System Development (BIOL 310) in the spring. In addition, she started work on her research focus, HSPs (heat shock proteins, here at Williams with the help of four research students: Courtney Juliano ’04, an honors student, who investigated the role of the small heat shock protein HSP27 in axon outgrowth in the zebrafish; Krista Harrison ’04, winter study and spring semester independent study student, who investigated the transcriptional regulation of the small heat shock proteins HSP27, HSPB2, and HSPB3; Kathryn Fromson ’06, research assistant, who studied adaptation of the heat shock response; and Meghan Ryan ’06, research assistant, who worked on an assay to test for phosphorylation of HSP27. Ms. Harrison presented her work at the Cold Spring Harbor Laboratory meeting on Molecular Chaperones and the Heat Shock Response, May 5-9. Ms. Fromson will be presenting some of her work at the 6th International Meeting of Zebrafish Development and Genetics, July 29-Aug. 2, in Madison, WI. Ms. Fromson and Ms. Ryan will continue with their research this summer, along with three new students who will be joining the lab. Professor Noah Sandstrom
Assistant Professor Noah Sandstrom conducted research examining hormonal
modulation of cognitive processes including attention and memory. Work
with students during the summer of 2003 investigated the influence of
androgens on memory retention and will be presented at the Society for
Neuroscience conference next fall. Along with his thesis student Nick
Bamat (‘04), he continued to examine the extent to which estrogens
may be neuroprotective. Using a variety of surgical, behavioral, and histological
techniques, they have shown that estrogens can minimize the damage that
results from transient global ischemia and gained some intriguing insights
in to the ways in which hormone dose influence outcome.
Professor Paul Solomon continued to serve as Clinical Director of the Memory Clinic and Clinical Neuroscience Research Center. He is currently principle investigator on 12 research grants from groups including the National Institute on Aging and several private research foundations. These grants are primarily for the evaluation of new drugs to treat Alzheimer's disease and related disorders. He gave more than 30 invited lectures at Medical Schools, Universities, and national and local meetings.
Professor Heather Williams attended the annual bird song workshop at the
Rockefeller University Field Research Center and presented work that formed
part of Jess Tierney’s (’03) honors thesis, which contributed
to defining the basis of laterality in vocal production in songbirds.
In the fall, a paper on the role of testosterone in limiting plasticity
in the learned song of adult male zebra finches, co-authored with two
former students, Denise Connor (’99) and Jennifer (Danforth) Hill
(’97) appeared in Hormones and Behavior. The paper was featured
on BioMedNet, a web site that highlights a few papers each week from among
a wide variety of journals. Prof. Williams’ lab continued its investigation
of the neural basis of song learning. Maria Kerr ('05) pursued the question
of whether zebra finches learn to time their courtship dances to their
songs and Whitney Johnson (’06) continued a project initiated by
Courtney Hunter (’03) looking into the question of whether the degree
of variability and flexibility in a bird’s song is inherited. Two
honors students, Greg Deplete and Tory Hendry (both ’04) put in
long hours in the lab. Greg used multi-unit recordings from the song centers
in the brains of adults to examine adults’ potential for brain and
behavioral plasticity, and Tory used microsatellite and dominant markers
to investigate the genetic structure of house finch populations. Prof. Williams served as a reviewer for the National Institutes of Health, and reviewed manuscripts for several journals.
Professor Betty Zimmerberg continued her research on the neural mechanisms
underlying behavioral responses to fearful situations and how experiences
of early deprivation, like child neglect, might impair developing coping
behavior. The research was supported by a grant from the National Science
Foundation, entitled “Early Experience and Neurosteroid Response
to Stress”. During the summer, Kristin Sageser ’04 continued
work on this project as part of her senior thesis, with an emphasis on
the effects of early deprivation on the development of play behavior.
Alyssa Fluty ’05 and Rui Nie ‘05 were also summer research
assistants, working on a new project using a novel animal model of anxiety,
rats bred for high and low rates of vocalization after brief maternal
separation. In November, both Kristin and Rui accompanied Zimmerberg to
New Orleans to present their research at the International Society for
Developmental Psychobiology annual meeting (“Comparison of early
stress models on subsequent alterations in social and communicative behavior
in rats” and “Long term effects of selective breeding for
infantile USV in rat pups on novelty suppressed feeding in adulthood”,
respectively). Also, in New Orleans, at a companion meeting, the Society
for Neuroscience annual meeting, was Nick Bamat ’04, presenting
research conducted in Zimmerberg’s Drugs and Behavior course (Psyc
312) with Michelle Kron ’04 and Andrew Schulte ’03 entitled
“Acute and long-term behavioral effects of toluene in neonatal rats
selectively bred for high or low vocalizations”. Rosemary Eseh ’04,
the other senior thesis student in Zimmerberg’s lab, investigated
the behavioral effects of iron deficiency during pregnancy in rats. Rosemary
won a coveted NIH travel award to present her research this summer in
Bordeaux, France, at the next meeting of the International Society for
Developmental Psychobiology. Betty Zimmerberg taught Introduction to Neuroscience in the fall and Drugs and Behavior in the spring. Zimmerberg was an external reviewer for the Psychology Departments at Bard and Lafayette Colleges, and served on the Woodrow Wilson Foundation Science Advisory Committee. Other professional activities included serving on the editorial board of Developmental Psychobiology, on the steering committee of N.E.U.R.O.N and as the chair of the membership committee of the International Behavioral Neuroscience Society. Zimmerberg was also was a grant reviewer for the Behavioral Neuroscience Program at the National Science Foundation and reviewed manuscripts for Behavior and Genetics, Developmental Psychobiology; Behavioral Neuroscience; Alcoholism: Clinical and Experimental Research; Physiology and Behavior; Psychological Reports: Perceptual and Motor Skills; and Neuropharmacology. Zimmerberg was also a co-PI with on two grants funded by the National Science Foundation out of the University of Albany – SUNY. And she really enjoyed teaching in the Williams College Summer Program for Teachers, giving a class entitled “Brain Soup: How Nature and Nurture Work Together.
Professor Steve Zottoli taught Neurobiology (Biology 304) in the fall
and Animal Physiology (Biology 205) in the spring. An independent laboratory
project was integrated into the laboratory of both courses. He also continued
to direct the Howard Hughes Medical Institute (HHMI) grant to Williams
College. Additionally, he has maintained is position as the President
of The Grass Foundation, a not-for-profit philanthropic organization that
funds various programs in neuroscience, and is also on the External Advisory
Board for Biomedical Research Infrastructure Network (BRIN) program for
the state of New Mexico, funded by NIH APPENDIX V: OUTSIDE SOURCES OF FUNDING
6/1/03-8/31/03.
"Research Experience for Undergraduate." National Science Foundation
Funding. $10,000 4/1/04-3/31/04.
Increasing U.S. Participation in 5th Pharmacology, Biochemistry, & Professor Paul Solomon Alzheimer's Disease Cooperative Study. "A Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Safety and Efficacy of Vitamin E and Donepezil HCL (Aricept®) to Delay the Clinical Progression from Mild Cognitive Impairment to Alzheimer's Disease. Alzheimer's Disease Cooperative Study. "A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Divalproex Sodium Therapy for Agitation in Nursing Home Residents with Probable or Possible Alzheimer's Disease." National Institute on Aging. Alzheimer's Disease Cooperative Study "A Phase IV Study of the Treatment of Agitation/Psychosis in Dementia/Parkinsonism (TAP/DAP)." National Institute on Aging. "A Phase II Pilot Study of the Safety, Tolerability and Pharmacokinetics / Pharmadynamics of Alzhemed in Patients with Mild to Moderate Alzheimer's Disease." Neurochem. "A Double - Blind, Placebo Controlled, Dose-Finding Study Evaluating the Safety and Efficacy of MKC-231, 80mg, b.i.d., and 20 and 80 mg q.d. in the treatment of Mild to Moderate Alzheimer's Disease." Mitsubishi Pharmaceuticals. Alzheimer's Disease Cooperative Study. "A Multi Center, Randomized, Double-Blind, Placebo Controlled trial of Simvastatin to slow the Progression of Alzheimer's Disease." National Institute on Aging. "A Phase II Double-Blind, Randomized, Dose-Ranging, Placebo-Controlled, Multicenter, Safety and Efficacy Evaluation of Three Doses of NS 2330 in Patients with Mild to Moderate Dementia of the Alzheimer's Type." Boehringer-Ingleheim Pharmceuticals. Alzheimer's Disease Cooperative Study. "A Randomized Double Blind Placebo Controlled Trail of Valproate to Attenuate the Progression of Alzheimer's Disease (AD)." National Institute on Aging. "A One-Year, Multicenter, Randomized, Double- Blind, Placebo-Controlled Evaluation of the Efficacy and Safety of Donepezil Hydrochloride (E2020) in Subjects with Mild Cognitive Impairment." Easai/Pfizer Pharmaceuticals. "A Randomized, Double-Blind, Placebo- Controlled, 4-Period Cross-Over Pilot Study of the Safety and Efficacy of Multiple Doses of ABT-089 in Subjects with Alzheimer's Disease." Abbott Pharmaceuticals. "A Dose-Ranging, Placebo-Controlled Study of SL65.0155-10 at the doses of 0.5 mg, 2 mg, and 8 mg for 12 Weeks in Patients with Mild-to- Moderate Alzheimer's Disease." Sanofi-Synthabolab. "A Multi-Center, Randomized, Open-label Study Evaluating the Effects of MKC-231, 80 mg b.i.d., vs Aricept, 5 mg or 10 mg, on Adrenal Function in Patients with Mild Alzheimer's Disease." Mitsubishi Pharmaceuticals.
APPENDIX VI: ESSEL-SPONSERED COLLOQUIUM SPEAKERS October
27th, 2003 March
8th, 2004 March
12th,, 2004 April
7th, 2004 April
26th, 2004 APPENDIX VII: YEAR 12 BUDGET AND EXPENDITURES
* The college-mandated weekly stipends continued to be $330, $30 more per week than in the original budget. Also, some students did not stay for the entire summer; two were only here for two weeks, one for three, and two more for five each. Additional students received support from other sources such as NSF or the Hughes Foundation. **Another new fulltime Neurobiology professor was hired, Lara Hutson, bringing our faculty to 6 (budgeted for 5). ***The Director receives a $4000 stipend and $4000 summer support. **** The College increased the mandated fringe benefits for the Junior and Senior Essel Fellows from original budget of 21% and 29%, respectively, to 32% for both. *****We are happy to apply $5,163 of our savings
from last year to cover the additional costs of this year that resulted
from increases in fringe benefits and the addition of two new full time
professors. We have considered these increased costs and the proposed
additions of two new budget items (student travel support funding and
support to attend the NARSAD and Society for Neuroscience Conferences)
in our proposal for 2004-2009. We would be happy to carry over our remaining
$1,509 to cover an overlap this summer of our new Junior Essel person
with Laurel Bifano, our current fellow, for a better training transition.
APPENDIX VIII: UPPER LEVEL NEUROSCIENCE CLASSES AND EMPIRICAL PROJECTS NSCI 401 - Topics in Neuroscience - Paul Solomon Neuroscientists explore issues inherent in the study of brain and behavior. The overall objective of this seminar is to create a culminating senior experience in which previous course work in specific areas in the Neuroscience Program can be brought to bear in a synthetic, interdisciplinary approach to understanding complex problems. The specific goals for students in this seminar are (1) to evaluate original research and critically examine the experimental evidence for theoretical issues, and (2) to gain an understanding of this discipline through group work, and oral presentations. Topics and instructional formats will vary somewhat from year to year, but in all cases the course will emphasize an integrative approach in which students will be asked to consider topics from a range of perspectives including molecular, cellular, systems, behavioral and clinical neuroscience. Previous topics have included memory, autism, depression, alcoholism, language development, and stress. Format: student-led discussions and presentations, three hours a week. Evaluation will be based on presentations, participation in class discussion, and a term paper. BIOL 204 - Animal Behavior - Heather Williams Making sense of what we see while watching animals closely is both an enthralling pastime and a discipline that draws on many aspects of biology. Explanations can be found on many levels. Evolutionary theory tells us why certain patterns have come to exist, molecular biology can help us understand how those patterns are implemented, neuroscience gives insights as to how the world appears to the behaving animal, and endocrinology provides information on how suites of behaviors are regulated. The first part of the course focuses upon how descriptive studies provide the basis for formulating questions about behavior as well as the statistical methods used to evaluate the answers to these questions. We then consider the behavior of individuals, both as it is mediated by biological mechanisms and as it appears from an evolutionary perspective. The second half of the course is primarily concerned with the behaviors of groups of animals from a wide variety of vertebrate and invertebrate species, concentrating upon the stimuli, responses, and internal mechanisms that maintain social systems and on the selection pressures that drive animals toward a particular social system. Format: lecture/laboratory, six hours per week. Evaluation will be based on examinations, lab reports, and a research paper.
This lecture-based course examines principles, patterns, and mechanisms of biological function from the level of cells and tissues to the whole organism. The themes of the course include structure and function, mechanisms of regulation, control and integration, and adaptation to the environment. Examples of these themes are taken from a wide variety of organisms with a focus on vertebrates. Laboratories provide practical experience in measurement and experimental elucidation of physiological phenomena and functional analysis of gross structure. Evaluation will be based on hour exams, laboratory practicals, laboratory reports, and a final exam. BIOL 304 - Neurobiology - Steve Zottoli This course is concerned with understanding the
biology of the nervous system, focusing primarily on the cellular bases
of neuronal function. Lectures will cover such topics as nerve resting
and action potentials, ion channels, neurotransmitters and synapses, and
the neural correlates of behavior in organisms with simple nervous systems.
Reading original research papers and discussing them constitutes an important
part of the course. Some of the topics that may be covered include: transmitter
release mechanisms, ion permeation through channels, plasticity in the
nervous system, and various clinical disorders. Laboratories are designed
to introduce the students to modern techniques in neurobiology including
extracellular and intracellular recording, histochemistry, and immunohistochemistry.
Format: lecture/laboratory, six hours per week. Evaluation will be based
on class participation, laboratory notebooks and posters, two hour exams
and a final exam. PSYC 316T - Clinical Neuroscience - Paul Solomon Diagnosing and treating neurological diseases is the final frontier of medicine. Recent advances in neuroscience have had a profound impact on the understanding of diseases that affect cognition, behavior, and emotion. This course provides an in-depth analysis of the relationship between brain dysfunction and diseased state. We will focus on neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and Huntington's disease. We will consider diagnosis of disease, treatment strategies, as well as social and ethical issues. The course is taught in the tutorial format and provides students with the opportunity to present material based upon: (1) review of published literature, (2) analysis of case histories, and (3) observations of diagnosis and treatment of patients both live and on videotape. Students design and conduct an empirical project. Format: tutorial. Evaluation based on position papers, class participation, and research project report. PSYC 312 - Drugs and Behavior - Betty Zimmerberg This course studies the relationship between behavior
and neurochemical changes in the brain. It begins with a detailed study
of neurotransmitter systems, drug-receptor interactions, and sources of
individual differences in drug response, such as gender and genetics.
Special topics include the behavioral consequences of prenatal drug exposure,
the role of classical and operant conditioning in the development and
maintenance of alcohol and drug abuse, the neural basis of reward, and
the interaction between cerebral lateralization and behavioral effects
of drugs. Format: lecture, discussion and required empirical project.
Requirements: an hour exam, an oral presentation, and a written report
of research. This course will have several short writing exercises, and
a final minimum 15-page paper that will be submitted in 4 sequential parts
with revisions. The emphasis is on learning how to write clear and elegant
scientific prose. PSYC 315 - Hormones and Behavior - Noah Sandstrom This course studies the relationship between hormones and behavior. We review the mechanisms by which hormones act in the nervous system. We also investigate how hormones influence behavior as well as how behavior and experiences alter hormonal function. Specific topics to be examined include: sexual differentiation; courtship, reproduction and parental behavior; aggression; and learning and memory. Students critically review data from both human and animal studies. Format: seminar. Requirements: midterm and final exams, seminar presentations and participation in discussions, written and oral presentation of final project. BIOL 310 - Neural Development - Lara Hutson Development can be seen as a tradeoff between genetically-determined
processes and environmental stimuli. The tension between these two inputs
is particularly apparent in the developing nervous system, where many
events must be predetermined, and where plasticity, or altered outcomes
in response to environmental conditions, is also essential. Plasticity
is reduced as development and differentiation proceed, and the potential
for regeneration after injury or disease in adults is limited; however,
some exceptions to this rule exist, and recent data suggest that the nervous
system is not as hard-wired as previously thought. In this course we will
discuss the mechanisms governing nervous system development, from relatively
simple nervous systems such as that of the roundworm, to the more complicated
nervous systems of humans, examining the roles played by genetically specified
programs and non-genetic influences. We will also discuss the similarities
and differences between development and regeneration, the extent to which
the nervous system is hard-wired, and the controversial idea that degeneration
represents "development in reverse." Format: lecture/discussion/laboratory,
six hours per week. Evaluation will be based on exams, short papers and
lab reports. BIOL 410 - Cell Dynamics - Lara Hutson Far from being static entities, individual cells can exhibit dynamic behaviors, sometimes migrating great distances or structurally reorganizing as in the formation-or reformation-of neuronal synapses. The ability of cells to move and reshape underlies a vast array of normal biological processes, including immune function, embryonic development, and memory formation, as well as abnormal processes such as cancer growth and metastasis. It is through precise regulation of polymerization, depolymerization, and contraction of the cellular cytoskeleton that motility is achieved, and we are just beginning to understand the genetic and biophysical bases of how this regulation occurs. Not surprisingly, imprecise regulation of the cytoskeleton can have serious consequences, and several disorders arise from defects in this process. In this course we will review the primary literature covering migration and motility. Format: discussion, three hours per week. Evaluation will be based on class participation and several short papers. Instructor Lara Hutson Description Reading material Evaluation I will be assigning questions for each set of readings. You will be required to keep notes on these, either in a separate notebook or on loose paper that can be kept in your gray notebook. Bring your notebook and the assigned readings to every class. I will collect your notebooks once during the semester for evaluation. (10% of grade) As this is a discussion course, you will naturally be expected to participate in class. (30% of grade) Attendance Office hours Honor code Your papers are expected to be your own work and are covered by the Statement of Academic Honesty as set forth in the Student Handbook, and the basic rules of attribution apply. Biol 410, Fall 2003 Bacterial chemotaxis Thurs. 9/11—Beyond signal transduction Sperm chemotaxis Amoeboid cells Tue. 9/23—Tubulin Thu. 9/25—paper 1 due Regulation of actin Thu. 10/2—Capping Tue. 10/7—Depolymerization/turnover 27. Aizawa, H., Sutoh, K. and Yahara, I. 1996.
Overexpression of cofilin stimulates bundling of actin filaments, membrane
ruffling, and cell movement in Dictyostelium. J. Cell Biol. 132, 335-344. Thu. 10/9—Nucleation/Branching: Arp2/3 Thu. 10/16—Nucleation/Branching: WASP/Scar Tue. 10/21—Cross-linking/Bundling Thu. 10/23—Paper #2 due Tue 10/28 & Thu. 10/30—Contraction and
Adhesion Tue. 11/4 & Thu. 11/6—Rho GTPases and
cell behavior Tue. 11/11 & Thu. 11/13—Rho GTPases:
regulation of Tue. 11/18—Paper #3 due Thu. 11/20 & Tue. 11/25—Proteolysis and
Membrane recycling
Description Readings Assigned readings are intended to supplement material covered in lecture, but will not always mirror lectures precisely. You will be responsible for all material we cover in lecture, whether it is included in the text or not. Copies of the Powerpoint files for lecture will be posted on Blackboard, but it may be useful to additionally obtain lecture notes from someone. Evaluation Honor code
Date Topics Readings Mar. 3 Quiz 1 and May 18 Final draft of paper due *References
NSCI 401 - Topics in Neuroscience - Heather Williams Neuroscientists explore issues inherent in the study of brain and behavior. The overall objective of this seminar is to create a culminating senior experience in which previous course work in specific areas in the Neuroscience Program can be brought to bear in a synthetic, interdisciplinary approach to understanding complex problems. The specific goals for students in this seminar are (1) to evaluate original research and critically examine the experimental evidence for theoretical issues, and (2) to gain an understanding of this discipline through group work, and oral presentations. Topics and instructional formats will vary somewhat from year to year, but in all cases the course will emphasize an integrative approach in which students will be asked to consider topics from a range of perspectives including molecular, cellular, systems, behavioral and clinical neuroscience. Previous topics have included memory, autism, depression, alcoholism, language development, and stress. Format: student-led discussions and presentations, three hours a week. Evaluation will be based on presentations, participation in class discussion, and a term paper.
How
are important conditions or changes in the environment received and transduced
by organisms? We will examine the molecular and cellular bases of the
Diagnosing and treating neurological diseases is the final frontier of medicine. Recent advances in neuroscience have had a profound impact on the understanding of diseases that affect cognition, behavior, and emotion. This course provides an in-depth analysis of the relationship between brain dysfunction and diseased state. We will focus on neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and Huntington's disease. We will consider diagnosis of disease, treatment strategies, as well as social and ethical issues. The course is taught in the tutorial format and provides students with the opportunity to present material based upon: (1) review of published literature, (2) analysis of case histories, and (3) observations of diagnosis and treatment of patients both live and on videotape. Students design and conduct an empirical project. Format: tutorial. Evaluation based on position papers, class participation, and research project report.
This
course studies the relationship between behavior and neurochemical changes
in the brain. It begins with a detailed study of neurotransmitter systems,
drug-receptor interactions, and sources of individual differences in drug
response, such as gender and genetics. Special topics include the behavioral
consequences of prenatal drug exposure, the role of classical and operant
conditioning in the development and maintenance of alcohol and drug abuse,
the neural basis of reward, and the interaction between cerebral lateralization
and behavioral effects of drugs. Format: lecture, discussion and required
empirical project. Requirements: an hour exam, an oral presentation, and
a written report of research. This course will have several short writing
exercises, and a final minimum 15-page paper that will be submitted in
4 sequential parts with revisions. The emphasis is on learning how to
write clear and elegant scientific prose.
This course studies the relationship between hormones and behavior. We review the mechanisms by which hormones act in the nervous system. We also investigate how hormones influence behavior as well as how behavior and experiences alter hormonal function. Specific topics to be examined include: sexual differentiation; courtship, reproduction and parental behavior; aggression; and learning and memory. Students critically review data from both human and animal studies. Format: seminar. Requirements: midterm and final exams, seminar presentations and participation in discussions, written and oral presentation of final project.
APPENDIX IX: REPORT ON THE 2002 WILLIAMS COLLEGE Dates:
June 9-August 17, 2003 Director: Steve Zottoli Funding support: Howard Hughes Medical Institute, Nan and Howard Schow and the Essel Foundation. Williams College ’03 Student Participants: Oliver
T. Burton ‘06 Preparation prior to going to the Marine Biological Laboratory: Two weeks were spent at Williams College preparing for the stay at the Marine Biological Laboratory (MBL) in Woods Hole, MA. The preparation consisted of lectures, readings, laboratory exercises and discussions (i.e., a short course in neurobiology). Students were provided with reprints of original literature pertaining to the research of those individuals who they would interact with at the MBL. They were encouraged to start reading this material. Students assembled a physiological recording station similar to the one they would use in Woods Hole. They tested the station by studying the stretch receptor of the crayfish (Crawdad, Sinauer). I encouraged collaboration between the group so that those students with more experience (3 rising seniors) could help instruct those with less experience (3 rising sophomores). I also used a “tutorial” approach to learning. Although I provided guidance and instruction when necessary, I required that the students take initiative in their own learning. Students were challenged to defend their positions when it seemed appropriate. Student scheduled activities while at the MBL: Once in Woods Hole, the day was divided to provide Williams students with an exposure to the diversity of teaching and research at the MBL. Students attended lectures in the morning, met with scientists at lunch, conducted research in the afternoon and attended seminars in the evening. The students were directed to certain lectures with the understanding that in many cases the material would be advanced (MBL courses are targeted at the graduate level). Past experience has indicated that as the students become more familiar with neuroscience, the lectures are easier to absorb. Social activities included cookouts, pizza parties and softball. Morning sessions: As was true last year, our laboratory space was contiguous with the MBL SPINES course (Summer Program in Neuroscience, Ethics and Survival). The individuals in the SPINES course are underrepresented minority students and they provided role models for the students in the Williams program. The Williams students and SPINES students attended morning lecture/laboratory sessions together for three weeks. The Williams students were invited by Joe Martinez, co-Director of the SPINES course, to attend all SPINES lectures and functions. Richard LeBaron, University of Texas San Antonio, directed morning sessions for the first week on tissue culture. Students learned dissection of the rat embryo brain to isolate hippocampal neurons, they learned how to dissociate and culture the neurons. Ruben Hernandez, University of Texas San Antonio, directed the second week and focused on electrophysiology of the the rat hippocampal slice. Students learned how to dissect and prepare a hippocampal slice for recording. They recorded extracellularly from the slice and evoked long-term potentiation (LTP). Steve Zottoli, Williams College, directed the third week and presented an introduction to studies of single cells in the vertebrate central nervous system. The Williams students taught the SPINES students the various experimental techniques they had learned over their first few weeks at the MBL. These techniques included: microelectrode pulling, dissection, and recording from single neurons in the cunner brain. The MBL is a world-renowned center for research
and teaching in the sciences. Many courses are given in the summer months
and after the 3-week session with the SPINES students was completed, Williams
students were asked to attend morning lectures in one or more of the following
courses: Embryology, Neurobiology, Neural Systems and Behavior, Methods
in Computational Neuroscience, Parasitology and Physiology courses. Lunch Sessions with MBL Scientists: The following schedule was arranged for students to meet with resident MBL neuroscientists during lunch. Students were required to read the papers (listed below) of these scientists before the meeting. I would typically meet with the students to discuss the papers before their scheduled meeting to insure that they understood the scientist’s hypothesis and how it was to be tested. Based on their readings, students prepared questions to ask the scientists. The discussion ranged from science to career paths, to ethics, etc. Meetings with specific scientists other than those listed were arranged on request assuming that the scientist in question was free to meet. Scheduled meetings with MBL scientists Scientist Topic Date Time Meeting place Felix
Schweizer Synaptic 6/25 noon Lillie steps Kamran
Khodakhah LTD 6/26 noon Lillie steps Pizza with SPINES 7/1 5pm MRC Dave
Bodznick Electroreception 7/2 noon Lillie steps Roxanna
Smolowitz Janis
Weeks Plasticity during 7/2 9pm Loeb, 1st floor Grae
Davis Synaptic 7/3 noon Lillie steps Joe
Fetcho Imaging of neurons noon Lillie steps Bob
Barlow Limulus 7/9 noon Lillie steps Steve Hadjuk Parisitology 7/16 noon Lillie steps Shelly
Segal Author 7/17 noon Lillie parking Roger
Hanlon Cephalopod 7/23 noon MRC Orian Shirihai Mitochondrial transporters 7/30 noon Lillie steps Dan
Barry M.D./Ph.D. to Astronaut 8/12 noon Lillie steps Liz
Jonas Recording from 8/13 noon Lillie steps
Visit of Mattias Gruhn from Cornell University from 7/12-7/15 to demonstrate procedures for recording chronically from crayfish nerves. Simone Bras worked with Jorge Moreira, University of Sao Paulo, Ribeirao Preto, Brazil. Researches post-terminal protein concentrations in the squid giant synapse using electron microscopy. Many of the students arranged private sessions with scientists. For example Michelle Kron met with Elaine Bearer from Brown to discuss M.D./Ph.D. programs.
An important part of the summer program involved an exposure to original research. Students worked as a team on the research project described below. The objective was to train each student in the techniques necessary to record from a single neuron in the vertebrate brain, and then to use these techniques to design and implement an original research project.
Physiological
studies on the dorsal cells in the cunner: Zottoli, S.J., Burton, O.T., Chambers, J.A., Eseh, R., Gutiérrez, L.M. and Kron, M.M. Transient Use of Tricaine to Remove the Telencephalon has no Residual Effects on Physiological Recordings of Supramedullary/Dorsal Neurons of the Cunner, Tautogolabrus adspersus Biol. Bull., 204 (in press) 2003.
Students were encouraged to attend Monday, Wednesday and Thursday evening seminars sponsored by the Neuroscience Institute at MBL. In addition they were encouraged to attend the Friday evening series on broad topics in biology. A list of the titles and speakers of the Friday evening series is given below:
Lillie Auditorium, 8:00 PM. Lectures are free and open to the public. Date:
Event: Other scheduled activities at the MBL: A series of activities were organized to broaden the exposure of the Williams Students to the vibrant scientific community at the MBL: A collecting trip on the MBL fishing vessel, Gemma (July 11), a pizza party (June 30th) and a number of Sunday cookouts were organized to allow social interaction between the SPINES group and the Williams group. We hosted the Williams College Summer Science Program for Minority Students for a day. The SSP is a 5-week program on the Williams College campus and exposes minority students who have been accepted to Williams College to basic material in English, mathematics, biology and chemistry. The SSP students drove down from Williams College, and we gave them a tour of the facilities, including our laboratory, as well as a series of presentations of the research conducted at the MBL. Prior to the arrival of the SSP students, the Williams students chose and prepared a presentation on one of the marine organisms commonly used for research at the MBL. This required that the Williams student had to learn about some natural history of the organism and the questions that were being addressed using this organism. The students practiced their presentations to other students in the group prior to the arrival of the SSP, and they wrote a short essay on the topic. The presentations were followed by a picnic.
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