Essel Program - 2008 Annual Report
The Neuroscience Program The Program in Neuroscience had another strong and successful year. Professor Noah Sandstrom received tenure. Dr. Laurel Pritchard, the outgoing Senior Essel Fellow, started her new tenure-track position as Assistant Professor of Psychology at the University of Nevada, Las Vegas. We are fortunate to have had Dr. Martha Marvin join us as the new role of Senior Essel Fellow; she had a busy and productive year with the program, teaching a section of the senior seminar as well as the lab program for our introductory course. Our Junior Essel Fellow, Tracey Van Kempen, completed her term and will begin graduate work towards her Ph.D. in Neuroscience at Cornell in the fall. This past year was also a successful one for the Program’s concentrators. In addition to the research assistants and independent study students conducting research with faculty members, there were thirteen Summer Essel Fellows in 2007. All eight of the graduating Summer Essel Fellows (class of ’08) will be pursuing research in neuroscience as they enter the post-baccalaureate world – as research assistants, graduate students, or MD/PhD students. John Rudoy, a former Essel Fellow and thesis student of Noah Sandstrom’s, received a prestigious NSF Fellowship. One highlight of the year was our students’ and program’s participation in the exchange of ideas within the wider neuroscience community. The program’s colloquium series, put together by Betty Zimmerberg (the outgoing Chair of the Neuroscience Program) was particularly strong and successful during the past academic year. Several students enjoyed the opportunity to attend NARSAD’s annual symposium in New York City. Still others attended scientific conferences and some presented their own work. Of particular note is that Kimberly Elicker was awarded the Undergraduate Student Poster Presentation Award by the American Association of Anatomists for her work on the “Characterization of the Zebrafish Small Heat Shock Protein Family”, a research project that she conducted under the supervision of Professor Lara Hutson. On the Williams College campus, the program’s course offerings were popular. Introduction to Neuroscience, the cornerstone of our program, was taught this year by Steve Zottoli and Noah Sandstrom and attracted nearly 100 students, and the senior seminar, the capstone of the program, needed to be offered as two sections to meet student demand. We have also started outreach programs to local schools; Noah Sandstrom has given a very successful presentation on brains to the fourth graders at the Williamstown Elementary School, and all of the school’s sixth graders dissected sheep brains in the lab at Williams College in a program organized by Heather Williams. Our faculty members continue not only to teach, publish scholarship, and supervise student research, but also to serve the wider college and scientific communities. Betty Zimmerberg chaired both the Psychology Department and the Neuroscience Program, and Steve Zottoli chaired the Biology Department. Both Betty Zimmerberg and Heather Williams served on grant review panels for the N.I.H., and several faculty members received funding from the N.I.H. and other outside sources. All have served as reviewers for scientific journals. Williams College has begun a cycle of reviewing interdisciplinary programs, and Neuroscience was one of the first to undergo such a review. This process included circulating petitions to past students, analyzing the responses, holding extended discussions, and writing a self-study report that answered specific questions raised by the review committee. Betty Zimmerberg ably shepherded us through this process. Not surprisingly, given the longevity and continued success of the program, the review was laudatory. The primary question raised by the review committee was whether the Neuroscience Program should, because of its success and size, consider becoming an independent department with its own faculty and major. At this time, we are not moving in that direction, but we will keep the possibility in mind for the future. I.
Undergraduate Research Fellows: During the summer of 2007, an unusual number of students holding Essel Fellowships performed research off-campus (two of our faculty members underwent medical procedures and were not able to supervise students). The off-campus fellowships proved to be valuable to the students, as can be seen by their accounts; although we will continue to emphasize research fellowships at Williams, we may also continue supporting off-campus summer research when and where it is appropriate. The research topics and accomplishments of the fifteen summer research students are listed in Appendix I. The titles and abstracts of the seven Neuroscience theses that were completed in 2004 can be found in Appendix II. 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: In addition to the introductory neuroscience course (NSCI 201) and the capstone course (NSCI 401), we offered five elective courses this year; two of the electives required the students to design and perform their own research project, and all of the elective courses gave students the opportunity to gain research experience. A complete listing and description of courses, including the syllabi of the two new courses, is located in Appendix VIII. IV. Essel Fellows: This was Dr. Martha Marvin’s first year as the Senior Essel Fellow in Neuroscience. Her teaching duties included the laboratory sections of foundation course for the program (Introduction to Neuroscience) and the spring section of the senior seminar (“Birth, Death and Stem Cells in the Adult Brain”). Her research program coordinated with that of Lara Hutson, and focused on the role of small heat shock proteins (sHSPs) in zebrafish development. Dr. Marvin’s work this year concluded a survey of the expression patterns of sHSPs over the first 48 hours of development (Marvin et al, 2008). At present, she is studying the effect of reducing expression of Hsp27 in early development. Loss of Hsp27 affects the early patterning of the nervous system, causing a reduction of posterior nervous system tissue. This patterning defect suggests that Hsp27 is necessary for one or more cellular signaling pathways essential to normal development. She presented these findings at the Zebrafish Development and Genetics Meeting. Such a role for small heat shock proteins would be a novel finding and would add significantly to our understanding of the protective effects of these proteins in development and stress. This summer Dr. Marvin is working with two Williams students, Christina Liu and Hannah Rosenthal, on her ongoing research project - identifying the pathways affected by reduction of Hsp27. Tracey Van Kempen completed her third year as the Junior Essel Fellow. She assisted in the teaching of the laboratory component of the Introductory Neuroscience course and served as the teaching assistant in Dr. Zottoli’s upper level Neurobiology course. Continuing her research with Betty Zimmerberg, Ms. Van Kempen had the opportunity to present her work at the Annual Meeting of the Society for Neuroscience in San Diego. During January, she had the opportunity to teach a Winter Study course exploring how animals and humans communicate and build relationships with each other. “Animal Communication: The Psychology of Human-Animal Relationships” examined the psychological and neurobiological principles of behavior, communication, and social bonding. Field trips to the local humane society, horse training facility, and a visit with an equine veterinarian provided experiential context for the students. In the fall, Ms. Van Kempen will be attending the Weill Cornell Graduate School of Medical Sciences pursuing a PhD in Neuroscience. 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. VII. Budget: Appendix VII presents the expenditures for year 11. An explanation of expenditures is also provided in that appendix.
APPENDIX I: 2007 ESSEL NEUROSCIENCE FELLOWS
APPENDIX II: ABSTRACTS OF NEUROSCIENCE HONORS THESES The Neuroprotective Effects of Acute Hippocampal Estradiol Injection in Ischemia Transient global ischemia is an event that causes a loss of blood flow to the brain, resulting in severe behavioral, spatial learning and memory and anatomical, cell death damage. This study uses a rat 4-VO model to create a transient global ischemia, and investigates the ability of an acute injection of estradiol directly into the hippocampus to lessen the damage associated with the ischemia. It also explores the mechanism that estradiol uses to be protective. Rats were given an acute injection of either estradiol or a vehicle immediately after the 4-VO and outcomes were based on performance on the c-MWM and h-MWM. The results suggest that estradiol is effective in mitigating the effects of the ischemia if administered directly into the hippocampus, suggesting that estradiol works in the hippocampus, and not in other, more remote, regions of the brain.
Note Order Variability in Directed Song Sequences: A Heritable Trait? Male zebra finches (Taenopygia guttata) sing consistent and stereotyped songs. Of their two types of songs, directed song (courtship song), sung to females, is more stereotyped, linear and consistent and is less variable in syllable structure than undirected song, sung alone or in the presence of other males. However, variability in note order was observed in the directed songs of a population of adult male zebra finches. In a previous study, birds with high and low note order variability were bred selectively for one generation (F2), and preliminary results indicated that the degree of note order variability may have been a heritable trait as suggested by Hunter (2003).
The Role of Torpor in Memory Consolidation in Mice Memory consolidation is the process by which new and labile information is stabilized as long-term memory. The consolidation of memories involves the formation of new cortico-cortical synapses, which is thought to be mediated by the hippocampus; and it is the formation of these new neuronal connections that solidifies newly learned information, thereby preventing degradation. This research analyzes the role of torpor, a hypometabolic state experienced by small rodents that is induced by cold ambient temperatures and low food availability, in the process of memory consolidation. Animals were trained on the Morris Water Maze (MWM) Hidden Platform task, and subsequently exposed to one of four experimental manipulations for 23 hours. Animals were either fasted at 19°C, fed at 19°C, fasted at 29°C, or fed at 29°C. All of the animals that were fasted at 19°C entered torpor while none of the animals in the other conditions experienced a torpor bout. Twenty-three hours after the initiation of the experimental manipulation, all animals were tested on the MWM in order to assess the consolidation of the memories previously learned. When tested 23 hours after learning, animals that were fed at 19°C and those that were fasted at 29°C did not demonstrate a bias toward the target platform, suggesting the existence of a disruption in the consolidation of newly acquired information. Animals that were fasted at 19°C, and therefore entered torpor, and animals that were fed at 29°C were capable of recalling the spatial memories learned during acquisition. These data demonstrate that the physiological changes that occur during torpor result in functional protection of the memory consolidation that is involved in hippocampally-dependent learning of spatial navigation tasks. Characterization of Points of Variability in Zebra Finch Song Song is a sexually dimorphic characteristic of the zebra finch (Taeniopygia guttata), an oscine songbird native to Australia and Timor. Song is used as a courtship strategy by males and is a learned trait (Immelmann 1969). Song is passed on through generations to listening juveniles, who, through a series of vocal imitation processes, construct their own song. However, in other oscine bird species, song learning is mediated by innate processes as well as by learned imitation (Gardner et al. 2005).
Development and Characterization of a Mouse Model of Transient Global Ischemia: Strokes and related ischemic events are one of the top three most common causes of mortality in developed countries. Given the prevalence and costs of stroke, ability to combat negative stroke outcomes would be a substantial contribution to healthcare. A compound of particular interest in this context is the hormone estradiol since it is protective against many forms of neurodegeneration, injury and insult, including several types of stroke. However, while estradiol acts as a neuroprotective agent, there are legitimate clinical concerns regarding its use because of a variety of adverse side effects associated with its use. Therefore, it is important to understand the mechanism through which estradiol is protective so that more targeted treatments can be developed. The most convincing explanation for estradiol protection is action through estradiol receptors, ERs. There are two classic ER subtypes, a and b and the involvement of each subtype in protection remains unclear. The current study characterizes a model of transient global ischemia in mice and evaluates the modulatory role of estradiol. Two-vessel occlusion, 2-VO is a model of transient global ischemia that involves reduction of blood flow to the brain via clamping of the common carotid arteries. Inability of ink injected into the left ventricle of the heart to reach the forebrain provided evidence that this is a feasible and reproducible stroke model. 2-VO caused region-specific cell death in the cortex, caudate and the hippocampus as measured with fluorojadeB, FJB, a marker for cell death. Longer durations of 2-VO also resulted in more severe mortality and more extensive damage in the hippocampal cell body layers. The interaction between region and ischemia duration was also significant, suggesting that different regions exhibit different susceptibilities to ischemic insult. The time course of expression of our marker for cell death, FluoroJade B, FJB, indicated that the number of FJB+ cells decreased marginally as soon as one week after insult throughout the hippocampal layers. Implantation of estradiol capsules prior to 2-VO reduced cell death selectively in the CA1 cell body layer. In sum, 2-VO is a suitable stroke model and estradiol reduces damage associated with 2-VO. These studies establish and characterize a model of transient global ischemia in mice, a particularly powerful development because it allows access to genetic technologies available only with mice that can be used to further probe the cellular underpinnings of this protection.
A Study of Electrphysiological Properties and Function of Supramedullary Cels (SMC) in the Green-Spotted Puffer, Tetraodon nigroviridis APPENDIX III: ESSEL SUPPORTED PUBLICATIONS AND PRESENTATIONS * indicates student author Lara Hutson
Marvin, MJ, O’Rourke, D*, Kurihara T*, Juliano, CJ*, Harrison, KL*, and Hutson, LD (2008) Developmental expression patterns of the zebrafish small heat shock proteins. Dev Dyn, 237, 454-63. Martha Marvin Marvin, MJ, O’Rourke, D*, Kurihara T*, Juliano, CJ*, Harrison, KL*, and Hutson, LD (2008) Developmental expression patterns of the zebrafish small heat shock proteins. Dev. Dyn., 237, 454-63.
Sandstrom, N. J. (in press). Sex differences in use of visual cues by rhesus monkeys performing a spatial learning task. Comment on "Cognitive performance in rhesus monkeys varies by sex and prenatal androgen exposure" by Herman and Wallen. Hormones and Behavior, 52, 139-142. Rowan, M. H.*, Williams, E.K.*, Sandstrom, N. J. (November, 2007). Neuroprotective effects of acute estradiol depend on the time of administration and the age of the rat. Society for Neuroscience Conference, San Diego, CA. Chuzi, S.E.*, Williamson, L.L.*, Crabtree, G.S.*, Cavigelli, S.A., Sandstrom, N. J. (June, 2007). Early life exploratory behavior predicts anxiety and corticosterone stress response, but not spatial learning, in adulthood. Society for Behavioral Neuroendocrinology Conference, Monterey, CA. Heather Williams Nathaniel T. Wheelwright, Meredith B. Swett, Iris I. Levin, Donald E. Kroodsma, Corey R. Freeman-Gallant, and Heather Williams (2008) The influence of different tutor types on song learning in a natural bird population. Animal Behaviour, 75, 1479-1493.
Zimmerberg, B., Van Kempen, T.A., Martinez, A.R*. & Brunelli, S.A. (November, 2007). Epigenetic effects of enriched environment housing on spatial learning deficits and hippocampal BDNF in high anxiety rats bred for an infantile vocalization phenotype. Presented at the Society for Neuroscience annual meeting, San Diego, CA. Pritchard, L.M., Van Kempen, T.A., Williams, H., Zimmerberg, B. (November, 2007). A laboratory exercise for a college-level, introductory neuroscience course demonstrating effects of housing environment on anxiety and psychostimulant sensitivity. Presented at the Society for Neuroscience annual meeting, San Diego, CA. Pritchard, L.M., Van Kempen, T.A., Zimmerberg, B. (November, 2007). Behavioral effects of repeated handling differ in rats reared in social isolation and environmental enrichment. Presented at the Society for Neuroscience annual meeting, San Diego, CA.
Greenwood, A.K., Peichel, K. and Zottoli, S. (2008) Does fast-start circuitry contribute to pufferfish inflation? JBJC abstract. Zottoli, S.J., Cioni, C. and Seyfarth, E.-A. (2008) Reticulospinal neurons in anamniotic vertebrates: A celebration of Alberto Stefanelli’s contributions to comparative neuroscience. 54th Convegno Gruppo Embriologico Italiano, Roma 4-7 giugno.
APPENDIX IV: NEUROSCIENCE FACULTY ACCOMPLISHMENTS Professor Professor Lara Hutson Lara Hutson was on leave all year, maternity leave during the fall and AP leave in the spring. During this time, she continued her research on how small heat shock proteins (sHSPs) regulate zebrafish development and protect the developing embryo from the effects of environmental stressors. Senior Essel Fellow, Martha Marvin, collaborated on this research, completing the work of characterizing the entire family of zebrafish small heat shock proteins. The results of this work were published in the journal Developmental Dynamics (Marvin et al., 2008). Kimberly Elicker ’09, Tahsin Khan ’10, and Nick Manice ‘09 also worked in the lab this year. Kimberly and Tahsin studied the roles of Hsp27 and HspB8 during development of motor axon projections, and Tahsin began to develop transgenic zebrafish models for Charcot-Marie-Tooth Disease and Distal Hereditary Motor Neuropathy, both of which can be caused by mutations in small heat shock proteins. Nick played an essential role in the lab assisting others with microinjections and tissue sectioning. Tahsin and Kimberly will continue their work in the lab during the summer of 2008, and we will be joined by two new students, Beth Links ’09 and Clare Malone ’09. Professor Noah Sandstrom Noah Sandstrom continued his studies examining the neuroprotective effects of ovarian hormones in rodent models of global ischemia. This work was conducted with seniors Gordon Crabtree ’08 and Erika Williams ’08. Gordon and Prof. Sandstrom explored the neuroanatomical sites at which estradiol acts to protect hippocampal neurons against global ischemia-induced cell death in rats. Erika and Prof. Sandstrom developed a mouse model of transient global ischemia and conducted several parametric studies of this model. In addition, they have developed a colony of estrogen receptor knockout mice that will be used to explore the cellular mechanisms underlying estradiol-mediated neuroprotection. Katie Jordon ’09 will continue this work in the coming year. Magali Rowan ’07 and Erika Williams ’08 were coauthors of a presentation with Professor Sandstrom at the annual meeting of the Society for Neuroscience held in San Diego, CA. In addition, research conducted as part of Sarah Chuzi’s ’07 senior thesis was presented at the annual meeting of the Society for Behavioral Neuroendocrinology in Monterey, CA.
Paul Solomon continued to teach in the areas of neuropsychology and behavioral neuroscience. He was responsible for the Clinical Neuroscience course taught this spring. He also continued his work on the evaluation of pharmacological treatments for Alzheimer's disease. This work was carried out in collaboration with several Williams neuroscience concentrators, including Carolyn Skudder and Nancy Haff, who worked on projects at The Memory Clinic in Bennington, VT. Dr. Solomon's work continues to be supported by grants from the National Institute on Aging as well as grants from the pharmaceutical industry. During the past year, Dr Solomon lectured widely throughout United States, Europe and Canada on diagnosis and treatment of Alzheimer's disease.
This year, Heather Williams' laboratory focused its attention on two primary issues: the basis of “syntax” in bird songs, and the long-term patterns of song learning and organization in the wild. Two honors students, Mildred Duvet ’08 and Charles Upton ’08, did their honors thesis work on the song syntax of zebra finches. These laboratory birds normally sing a string of notes in a linear sequence, but some birds vary this structure more than others. Mildred Duvet quantified the songs of many adult male zebra finches bred in aviaries selected for birds with high- and low-variability songs, and compared the variability in song syntax to a number of brain and physiological measures. She found that variability in song syntax is not tightly correlated with the volumes of specific song nuclei or with the testosterone levels of the birds, and her work suggests that details of neuronal wiring rather than heritable brain traits are responsible for differences between birds in the variability of song syntax. Charlie Upton approached the same general problem from another angle: he examined features of syllables and related those to how often birds varied their syntax at specific points within the learned song. He found that birds tend to alter their syntax most often at points defined by specific syllable types and locations within the string. Together, Mildred and Charlie’s work suggest that syntax variation arises as a result of song learning rather than genetically determined brain features. During the fall semester, Prof. Williams taught Animal Behavior. This course can be slanted in many different ways as different instructors at different institutions may choose to emphasize evolutionary, ecological, or neuroscience-related approaches. At Williams College, although we do not neglect evolution and ecology, the course (not surprisingly) considers the neural basis of many animal behaviors, including bat echolocation, bird song learning, frog mate choice, pair formation in voles, and the “personality traits” behind baboon aggression. Professor Williams was on sabbatical in the spring, and spent almost three weeks of that time alone on an island in the Bay of Fundy recording, capturing, banding, measuring, and mapping the territories of male Savannah sparrows as part of a long-term study. The goal of this study is to use insights gained in the laboratory working with birds such as zebra finches to understand how individual learning of songs affects the structure of songs within a population – both in how they are spaced out in a given year and how they population changes over time. The first paper about learning of songs in this species appeared this year (see below). Three students – Danielle Perszyk ‘09, Daniel Tao ‘10 (both Essel Fellows), and Jon Cavanaugh – joined Prof. Williams in attending the annual Bird Song Conference held at the Rockefeller University. This conference, which Williams co-founded, has proven to be highly successful and is now in its 12th year. In work performed with Nathaniel Wheelwright and other co-authors, she published "The influence of different tutor types on song learning in a natural bird population" in the journal Animal Behaviour. In February, Professor Williams served as a panelist for an N.I.H. study section (IFCN-5).
Professor Betty Zimmerberg continued her research on the effects of early social stress on the neural mechanisms underlying behavior. Ashley Martinez ‘09 and Lindsay Moore ’09 conducted experiments in the summer of 2007 on the effects of neonatal isolation on olfactory associative learning and BDNF in the olfactory bulbs and hippocampi of week-old rats. In the fall, Ashley also conducted an independent study project looking at the effects of gestational treatment with the neurosteroid allopregnenolone on maternal behavior in a line of rats genetically bred for increased anxiety. During Winter Study, Cate Cho ’10 and Jim Dunshee ’09 conducted independent research on vocalization behavior of adult rats in lines bred for high and low rates of vocalization after brief maternal separation. Tracey Van Kempen ’05, the Essel Foundation post-baccalaureate fellow, was an admirable technical assistant in all of these studies, and Shivon Robinson ’11 was an excellent research assistant. Professor Zimmerberg also sponsored off-campus lab internships by Nicole Sanders ’08, Douglas Washington ’08 and Michael Kirwan ’08. Zimmerberg taught the Program’s senior seminar in the fall of 2007, focusing on novel neurotransmitters and retrograde messengers in synaptic and behavioral function. She also sponsored an independent study by Lindsay Moore ’09 on Neuroethics. In the spring, she taught her seminar "Image, Imaging and Imagination: The Brain and Visual Arts". This class examined topics at the intersection of psychology, neuroscience and art such as retinal neurobiology, cortical organization and perception of color and form, how visual artists have used or challenged perceptual cues in their work, and how the brain perceives faces and how that influences appreciation of portraiture. They also considered the influence of neurological and psychological disorders in artists on their work. In addition to regular seminar discussions, this class met several times in area museums and took a field trip to a New York City gallery. Zimmerberg served on the NSF’s SOMAS Grants Review Board and was an ad hoc reviewer for Behavioral Neuroscience and Neuroendocrinology grants for the NSF. Other professional activities included serving on the editorial board of Developmental Psychobiology and reviewing manuscripts for Developmental Psychobiology; Behavioral Neuroscience; Behavioural Brain Research; Pharmacology, Biochemistry and Behavior; Alcohol; Progress in Neuro-Psychopharmacology & Biological Psychiatry; Biological Psychiatry. In May, Zimmerberg attended Tufts University Conference on Emerging Trends in Behavioral, Affective, Social, and Cognitive (BASC) Neurosciences on the Cognitive Neuroscience of Visual Knowledge: “Where Vision Meets Memory”.
Steve Zottoli began his first year as Chair of the Biology Department. During the fall semester, Zottoli team-taught Introduction to Neuroscience with Noah Sandstrom in Psychology. In the spring, he taught an upper level Neurobiology course which had been bracketed for a number of years. He mentored two Honors Students, Tina Wong ’08 and Jarrad Wood ’08. A long-term goal of the Zottoli laboratory is to understand the neuronal basis of behavior and the recovery of behavior after spinal cord injury. Tina Wong studied physiological properties of supramedullary neurons in the pufferfish and successfully recorded from these neurons in a free-swimming fish. Jarrad Wood studied the response of central nervous system glial cells and blood-born reactive cells to a minimal wound of a single axon (the Mauthner axon) in the brain of the goldfish. Zottoli continues to spend summers at the Marine Biological Laboratory in Woods Hole, MA where he conducts research and is a faculty member in the SPINES (Summer Program in Neuroscience, Ethics and Survival) course. Tina Wong ’08 spent the summer at the MBL with Zottoli studying the function of supramedullary neurons in fishes. Zottoli is a Life Trustee of The Grass Foundation, a not-for-profit philanthropic organization that funds various programs in neuroscience. He continues collaborative research projects with Melina Hale at the University of Chicago, Ed Gilland and Hans Straka at the MBL, Don Faber at Albert Einstein College of Medicine and Joe Fetcho at Cornell University.
APPENDIX V: OUTSIDE SOURCES OF FUNDING
National Eye Institute (NIH) R03 Small grants for pilot research for: “Small heat shock proteins and retinotectal development,” 8/1/04-7/31/07 with no-cost extension through 7/31/08 ($373,868). NIH R15 “Motor axon development in a zebrafish model of Charcot-Marie-Tooth disease,” 8/1/08-7/31/10 ($220,076) Professor Noah Sandstrom 7/1/05 – 6/30/08. “Estrogen and Cognition Following Ischemia.” National Institutes of Health. $213,007. (1 R15 NS052911-01) Professor Paul Solomon Alzheimer's Disease Cooperative Study. "A Randomized, Double-Blind, Placebo-Controlled Trial of Valproate to attenuate the progression of Alzheimer's Disease." National Institute on Aging. Principal Investigator --Sanofi-Synthabolab. “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.” Principal Investigator – Wyeth Research. “A 3-Month, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Safety, Tolerability, and Efficacy Study of 3 Doses of SRA-333 in Outpatient with Mild to Moderate Alzheimer’s Disease with Donepezil as Active Control.” Principal Investigator – Eisai, Inc. "A 1-Year, Double-Blind, Randomized, Placebo-Controlled Study Of Rasagiline 1mg And 2mg Added to Aricept 10mg Daily in Patients with Mild to Moderate Dementia of the Alzheimer's Type." Principal Investigator - Saegis, “A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Efficacy and Safety of SGS742 in Subjects with Mild to Moderate Alzheimer’s Disease.” Principal Investigator - Sanofi-Synthelabo. “A Randomized, Multicenter, Double-Blind, Placebo-Controlled, 18-Month Study of the Efficacy of Xaliproden in Patients with Mild-to-Moderate Dementia of the Alzheimer’s Type.” Principal Investigator - Elan Pharmaceuticals. “A Phase IIa, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose, Safety, Tolerability, Pharmacokinetic, Pharmacodynamic, and Immunogenicity Trial of AAB-001 in Patients with Mild To Moderate Alzheimer’s Disease.” Principal Investigator Voyager Pharmaceutical Corp, “A Double-Blind Placebo-Controlled Study Of Vp4896 For The Treatment Of Mild To Moderate Alzheimer’s Disease.” Principal Investigator - Myriad Pharmaceuticals. “Phase 3 Multicenter, Randomized, Double Blind, Placebo Controlled Study Of The Effect Of Daily Treatment With Mpc-7869 On Measures Of Cognition, Activities Of Daily Living And Global Function In Subjects With Mild Dementia Of The Alzheimer’s Type.” Principal Investigator - Sanofi Aventis, "A Fifty-Two-Week Multicenter Open-Label Study Evaluation The Long-Term Safety And Tolerability Of Saredutant In Adult And Elderly Patients With Major Depressive Disorder." APPENDIX VI: ESSEL-SPONSERED COLLOQUIUM SPEAKERS Magdalene Moran ‘96, Ph D, Hydra Biosciences Magdalene Moran is Senior Director of Biology at Hydra Biosciences, a biopharmaceutical company founded in 2002. Her research group focuses on drug discovery of small-molecule regulators for ion channels. TRPs (Transient Receptor Channels) are neuronal ion channels that relay information into and out of the cell. Specific TRP channels are involved in pain, hypertension and inflammation. Hydra Biosciences' first TRP channel blocker may be indicated for treatment of arthritis, chronic and acute pain. As the first in a novel class of pain relievers and anti-inflammatory drugs, it may avoid the side effects caused by opiates and NSAIDs (non-steroidal anti-inflammatory drugs). Additionally, she directs research on modulators of the CatSper (Cation Channel of Sperm) ion channels. CatSpers are found in the tail of mature sperm and are required for fertilization. Blockers of CatSper function are potential non-hormonal contraceptives.
Nathan Fox ‘70, PhD, University of Maryland, College Park After graduating with Honor is Political Science from Williams College, Dr. Fox went on to study for his doctoral degree in Psychology and Social Relations at Harvard University. Dr. Fox is currently the Director of the Child Development Lab at the Institute for Child Study in the Department of Human Development at the University of Maryland, College Park. His research focuses on socio-emotional development in children, including temperament, development of emotion and emotion regulation, psychophysiology, and infant cognitive/social development. Of particular interest to his lab is the observation and measurement of attention, memory, as well as emotion expression and social experience. In his research, Dr. Fox links these psychological processes to neural activity through brain imaging methods such as EEG, ERP and functional neuroimaging.
Judy Willis ’71, M Ed, MD, RADteach.com Dr. Willis '71 received her M.D. from the University of California at Los Angeles School of Medicine and her M.Ed. from the University of California at Santa Barbara. After practicing as an adult and child neurologist for 15 years, she decided to pursue a career in education. Since then, she has been teaching middle school and infusing her classroom practices with her expertise in neurology. Her research focuses on RAD learning, an acronym that stands for the parts of the neural system that are particularly active in learning and memory: Reticular activating system, Amygdala, and Dopamine. She also defines RAD as "reach and discover" for the less-scientifically inclined among her audience. She is the author of a number of books, including "Research-Based Strategies to Ignite Student Learning: Insights from a Neurologist/Classroom Teacher" (2006),”Brain-Friendly Strategies for the Inclusion Classroom" (2007), and "How Your Child Learns Best: Insights from a Neurologist and Classroom Teacher" (upcoming, 2008). Willis also writes extensively for professional educational journals and was honored as a 2007 Finalist for the Distinguished Achievement Award by the Association for Educational Publishers.
Peter Tyack, Ph D, Woods Hole Oceanographic Institute Dr. Tyack is as Senior Scientist and Walter A and Hope Noyes Smith Chair in the Biology Department of the Woods Hole Oceanographic Institution. His research focuses on the social behavior and acoustic communication in whales and dolphins as well as vocal learning and mimicry in their natural communication systems. In particular, Dr. Tyack is investigating what the structure and function of whale songs can reveal about how whales and dolphins respond to human noise, as well as the social function of these songs among cetaceans. Developing methods to identify which cetacean produces a sound within a social group of conspecifics along with new techniques to tag whales, locate their calls, and monitor vocal and social behavior of marine mammals is a crucial part of furthering this investigation. He has been involved in the design, planning and fieldwork for a series of experiments investigating the possible impact on marine mammals of human-made sources of noise.
Chi-Bin Chien, Ph D, University of Utah School of Medicine After receiving his Ph.D. 1991 from the California Institute of Technology, Dr. Chien held post-doctoral fellowships at both the University of California San Diego and the Max Planck Institute for Developmental Biology in Germany prior to his current position as Associate Professor of Neurobiology and Anatomy at the University of Utah School of Medicine. Dr. Chien’s research uses the zebrafish as a model system to understand how genetic and molecular mechanisms control cell behavior in vivo. Many of the signaling molecules that are critical for development have now been identified: for instance, guidance ligands and receptors during axon and vascular guidance, and morphogens and transcription factors during embryonic patterning. It is much less clear how these molecules function in cells during development, and furthermore how multiple signaling pathways are orchestrated as the embryo develops.
Bevil Conway, Ph D, Wellesley College, McLean Hospital, and Harvard Medical School Dr. Conway is a neuroscientist and artist, and is the Knafel Assistant Professor of Natural Science at Wellesley College. His research examines the neural basis for visual behavior, with a particular focus on color vision. Dr. Conway is particularly interested in investigating the relationship between visual processing and visual art -- what can art tell us about how the brain works? Can neuroscience, vice versa, inform our understanding of visual art?
APPENDIX VII: YEAR 16 BUDGET AND EXPENDITURES
During 2007-8 academic year (the 2008 fiscal year), the Essel budget was underspent by $7,308. Substantially less was spent on the Senior Essel Fellow’s salary than budgeted because 20% of that salary was paid by Williams College to cover the Fellow’s teaching assignment; some of this savings was cancelled by the higher-than-budgeted fringe benefit rate. In addition, the funds budgeted for the Essel Neuroscience Conference were not spent (the conference was held in 2006-7). Student travel and housing was slightly overspent, as several students worked on projects off-campus. We anticipate applying the unspent funds to the following fiscal year, as several fixed costs (for example, student stipends and fringe benefits, which are set by the college) have risen more rapidly than anticipated in the original budget.
APPENDIX VIII: UPPER LEVEL NEUROSCIENCE CLASSES AND EMPIRICAL PROJECTS BIOL 204 - Animal Behavior – Heather WilliamsMaking 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, 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.
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.
INTR 223 - Image, Imaging and Imagining: The Brain and Visual Arts – Betty Zimmerberg The brain interprets the visual world and generates cognitive and emotional responses to what the eyes see. It is also responsible for creating visual objects. This course first examines how we see and how our brains organize and perceive what we see. In that context, we will investigate how visual artists have used or challenged perceptual cues in their work. We then will study Gestalt perceptual laws and illusions, and see how they have been used in works of art. We will also consider the influence of "disturbed" brain function of artists on their work (for example, autism, schizophrenia, and epilepsy). In the second unit, we will discuss the history and use of neuroimaging (brain scans), and the questions posed by Dumit's ethnography of neuroimagers, "Picturing Personhood," for example, how neuroimages are used in public discussions of mental illness, violence, and addiction. We will also examine neuroimaging studies questioning whether the brains of visual artists are lateralized or specialized differently from non-artists. In the final unit, we will explore how visual artists are using brain images in their artwork, and how they have portrayed brain syndromes and mental states. The course will culminate with the development of an exhibit. PSYC 315 - Hormones and Behavior – Noah SandstromIn all animals, hormones are essential for the coordination of basic functions such as development and reproduction. This course studies the dynamic relationship between hormones and behavior. We will review the mechanisms by which hormones act in the nervous system. We will also investigate the complex interactions between hormones and behavior. Specific topics to be examined include: sexual differentiation; reproductive and parental behaviors; stress; aggression; and learning and memory. Students will critically review data from both human and animal studies. All students will design and conduct an empirical research project.
PSYC 316 - Clinical Neuroscience – Paul SolomonDiagnosing 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 disease 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 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. All students will design and conduct an empirical research project. Format: Empirical Lab Course. Evaluation will be based on position papers, class participation, and research project report.
NSCI 401 - Topics in Neuroscience - Betty Zimmerberg, Martha MarvinTo 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.
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