Neurobiology

C303 Sterling Hall of Medicine, 785.4323
http://info.med.yale.edu/neurobio/
M.S., M.Phil., Ph.D.

Chair
Pasko Rakic

Director of Graduate Studies
Amy Arnsten (SHM B428, 785.4431, amy.arnsten@yale.edu)

Director of Medical Studies
Michael Schwartz (SHM C327B, 785.4324, michael.schwartz@yale.edu)

Professors
Amy Arnsten, Colin Barnstable, Benjamin Bunney, Pietro De Camilli, Nihal de Lanerolle, Joel Gelernter, Charles Greer, Tamas Horvath, Jeffery Kocsis, Robert LaMotte, Csaba Leranth, David McCormick, Marina Picciotto, Pasko Rakic, Joseph Santos-Sacchi, Ilsa Schwartz, Gordon Shepherd, Stephen Strittmatter, Xiao-Jing Wang, Stephen Waxman

Associate Professors
Meenakshi Alreja, Hal Blumenfeld, Charles Bruce, Michael Crair, Sabrina Diano, Murat Gunel, Anthony Koleske, Daeyeol Lee, Michael Schwartz, Ning Tian, Flora Vaccarino, Christopher van Dyck

Assistant Professors
Stacy Castner, Wei Chen, Mark Laubach, James Mazer, Dhasakumar Navaratnam, Nenad Sestan, Graham Williams, Mark Yeckel

Fields of Study

Fields include the development, neuronal organization, and function of the mammalian central nervous system. The range of methods includes molecular and cellular neurobiology, neuroanatomy, receptor biochemistry, neuropharmacology, neurophysiology, and behavior. An integrative, multidisciplinary approach is encouraged.

Special Requirements for the Ph.D.

Course Requirements

Six courses are required, and students must obtain a grade of Honors in two of these courses and maintain an HP average. Required courses are Principles of Neuroscience (NBIO 501a), Neurobiology (NBIO 720a), and Structural and Functional Organization of the Human Nervous System (NBIO 500b). Three more elective graduate-level courses are required. In addition to these six science courses, students must also take the Bioethics course.

Laboratory Rotations

Two rotations are required; typically completed in the first year. Rotations outside the Neuroscience track will count toward this requirement upon approval of the Neuroscience track directors.

Teaching Requirements

An important aspect of graduate training in Neurobiology is the acquisition of teaching skills through participation in courses appropriate for the student’s scientific interests. These opportunities can be drawn from a diverse menu of lecture, laboratory, and seminar courses at the undergraduate, graduate, and medical school levels. Ph.D. students are required to serve as Teaching Fellows (TF) for two terms. First-year students may not serve as a TF without written permission from the Neuroscience track directors. It is recommended that one term of teaching should be completed by the end of the third year, and both requirements be completed by the end of the fourth year.

Specifically, it is recommended that the first requirement be met by teaching in either Principles of Neuroscience (NBIO 501a), Neurobiology (NBIO 720a), Brain and Thought (CGSC 201a), or Structural and Functional Organization of the Human Nervous System (NSCI 510). The second course may be chosen from the list of neuroscience-related courses in the Graduate School of Arts and Sciences bulletin, or from the INP Bioethics course. A course not directly related to neuroscience must have the approval of the DGS.

Qualifying Exam

Ph.D. students must complete their qualifying exam before the end of their second year as a graduate student. The student must choose four faculty members to read with; it is strongly encouraged that these faculty represent interests spanning from molecular to systems/cognitive neuroscience. The student and faculty should devise a reading list of about fifteen papers on a defined topic. They should meet regularly (at least three or four meetings) to discuss the papers in depth. For the written exam, the student is given two questions from each faculty member. The student has three hours to write an answer to one of the two questions for each faculty member, i.e., a twelve-hour written exam spread over two days. The exam is performed on a laptop observing the honor system and is proctored by the DGS. The student may refer to the papers and his/her notes but not to the Internet. The answers are distributed to the faculty, and several days later an oral exam is held to further evaluate the student’s knowledge. A fifth faculty member (a reader) chosen by the student is also present at the oral exam, along with the DGS. If the student fails the qualifying exam, he/she may have one more attempt at passage; this must be completed within one term of taking the original exam.

Prospectus

Ph.D. students must complete and submit their dissertation prospectus (also called thesis proposal) by the end of the third year as a graduate student. The guidelines are as follows:

The student should discuss with his/her mentor an appropriate topic and research plan for the thesis proposal, as well as discuss likely names of faculty to serve on the thesis committee.
The student should write a proposal of approximately ten pages (similar to an NRSA application). This should include (a) the hypothesis to be addressed, (b) a few pages of background and significance, (c) preliminary data to demonstrate feasibility, and (d) a research plan including strategies in case proposed experiments fail. It is highly recommended that the thesis include a core of conservative experiments, i.e., very feasible, well-controlled studies. High-risk/high-payoff studies should only be included as “halo” research; i.e., if these fail, the student should still be able to graduate.
The mentor should approve the thesis proposal.
The student should distribute the proposal to his/her thesis committee members at least several days before the thesis committee meeting, and optimally discuss the proposal with each member individually prior to the meeting to ensure that there are no major problems. The thesis committee is required to have four members: the mentor and three other faculty, with at least one of those three faculty from outside the Neurobiology department. Faculty outside of Yale can be included if they can attend on a regular basis. Non-Yale faculty are often best included as a fifth member, so that a meeting can officially be held in their absence if needed.
The student meets with the thesis committee to approve the thesis proposal. It is at this time that the proposal is often modified, for instance by the suggestion of an additional control experiment. Goals should be realistic and in the interest of the student completing his/her degree in a timely manner. The finalized approved protocol is then provided to the Neurobiology business office, where the registrar will complete the paperwork for advancement to candidacy and send it to the Graduate School. As this must be completed before September 1, it is hoped that students will convene the thesis committee meetings prior to August 1.

The student should meet with his/her thesis committee on a yearly basis to update progress and problems. A one-page summary of this meeting, signed by the mentor and the DGS, should also be given to the business office to reside in the student’s file.

Admission to Candidacy

Ph.D. students are required to have been admitted to candidacy by the end of the third year as a graduate student. Generally, the submission of the thesis prospectus is the final requirement for admission to candidacy and paperwork for both is submitted to the Graduate School at the same time.

Other Requirements

All graduate students who are admitted to candidacy are required to have an annual thesis committee meeting. All graduate students are required to give a student research presentation annually (a brief INP rotation talk early in the graduate career, followed by a longer Neurobiology Student Research Talk as the student’s research advances). All students are expected to attend rotation/student research talks.

Thesis Defense

There are several parts to the thesis defense: (1) The student gives the thesis document to the thesis committee with sufficient time for them to read this large document. (2) The student defends the thesis in front of the thesis committee. It is expected that small changes will be made before submitting the final document to the Graduate School. If substantial changes are needed, the defense must be delayed. (3) The student gives the public defense, a one-hour seminar summarizing the research and open to the community. The seminar follows successful defense before the committee. These can be several days apart, but should not be more than a week apart without permission of the DGS.

Special Requirements for the M.D./Ph.D.

Course Requirements

Five courses are required; students must obtain a grade of Honors in two of these courses, and this must be achieved in the first two years of the combined program. Required courses are Principles of Neuroscience (NBIO 501a) and Structural and Functional Organization of the Human Nervous System (NBIO 500b). Three more elective graduate-level courses are required. The following courses taken during the first two years of medical school will count toward the student’s elective requirements in the Neurobiology program, provided the student has registered to receive a graduate grade in the course: CBIO 502, CBIO 601, GENE 500b, MB&B 800a, Physiology 500. In the case of students accepted into the M.D./Ph.D. program during their first year of medical school, a letter from the faculty member in charge of the first-year course indicating the grade achieved in the course is required and an official transcript from the School of Medicine must be submitted to the Graduate School.

Laboratory Rotations

Two rotations are required; rotations in another department/program will count toward this requirement upon approval of the Neuroscience track directors.

Tteaching Requirements

M.D./Ph.D. students are required to serve as Teaching Fellows (TF) for one term; two terms are preferred. Previous teaching (as TF) in the histology labs or courses in MCDB does count toward this requirement as long as the student has taught while enrolled at Yale as an M.D./Ph.D. student.

Qualifying Exam

M.D./Ph.D. students must complete their qualifying exam before the end of their first year as an affiliated graduate student. Thus, if the student affiliates at the customary 21⁄2-year point (beginning of the spring term of the third year of matriculation at Yale), he/she must complete the examination before registering for the spring term of the fourth year at Yale.

Prospectus

M.D./Ph.D. students must complete and submit their dissertation prospectus (i.e., thesis proposal) by the end of the second year as an affiliated graduate student. Thus, if the student affiliates at the customary 2-1⁄2-year point, he/she must submit the approved prospectus before registering for the spring term of the fifth year (at the beginning of year 3 as an affiliated graduate student).

Please note that every dissertation prospectus must be approved by the thesis committee.

Admission to Candidacy

M.D./Ph.D. students are required to have been admitted to candidacy by the end of the second year as an affiliated graduate student. Generally, the submission of the dissertation prospectus is the final requirement for admission to candidacy and paperwork for both is submitted to the Graduate School at the same time.

Other Requirements

All graduate students who are admitted to candidacy are required to have an annual thesis committee meeting. All graduate students are required to give a student research presentation annually (a brief INP rotation talk early in the graduate career, followed by a longer Neurobiology Student Research Talk as the student’s research advances). All students are expected to attend rotation/student research talks.

Affiliation requirement: A copy of the student’s application to the M.D./Ph.D. program, a copy of the student’s current transcript, and notation of rotations completed must be submitted to the Neurobiology program business office. The DGS must have this information in hand before the official M.D./Ph.D. student affiliation form can be approved. The Neurobiology program business office requests that copies of transcripts for all affiliated M.D./Ph.D. students be forwarded when they are received by the M.D./Ph.D. office.

Timeline

Year One: M.D./Ph.D. students complete courses in the School of Medicine and register for selected courses in the Graduate School. Most who identify Neuroscience as their probable Ph.D. field will take the required course, Principles of Neuroscience, in the fall term. This is the recommended timing. M.D./Ph.D. students should take NBIO 500b in the spring for graduate school credit/grade. Other electives as listed above may be taken for graduate school credit to fulfill our requirements, and indeed, it is recommended that this be done. Two laboratory rotations should be completed in the summer. The DGS’s of both the Neurobiology program and the INP may be of assistance in identifying appropriate laboratories based on the student’s interests.

Year Two: Courses in the School of Medicine are typically taken. Part 1 of the Boards is taken.

Year Three: By January of the third year, a thesis lab should be identified and all paperwork should be completed (affiliation form completed and copy of student’s academic record including application transferred to the Neurobiology business office). Student’s stipend is supplemented by PI/PI’s primary department at time of affiliation.

Year Four: The Qualifying Examination must be completed within one year of laboratory/program affiliation. Registration for the following term will be denied if this requirement is not fulfilled in a timely manner. Typically this will be fulfilled before the spring term of the fourth year.

Year Five: The dissertation prospectus must be approved and submitted to the Graduate School by the end of the second year of laboratory/PI affiliation. Typically, this is by the end of the fall term of year five. Registration for the following term will be denied if this requirement is not fulfilled in a timely manner. The Thesis Committee approves the prospectus, and required paperwork is then delivered to the Neurobiology program business office by the student. The Neurobiology program business office will then complete the Admission to Candidacy paperwork and submit it to the Graduate School. The prospectus must be submitted to the Graduate School at least six months before the dissertation is submitted.

Year Six: Typically an M.D./Ph.D. student will complete and defend his/her dissertation at the end of the fall term or the beginning of the spring term. We require that M.D./Ph.D. students defend their dissertations before returning to fulfill the remaining School of Medicine requirements.

Year Seven: Student completes all remaining requirements and graduates in May.
While this is considered a guideline for a typical M.D./Ph.D. student, we recognize that not every student will follow this path. Any digression from this timeline must be discussed and approved by the DGS, with appropriate notes to the student’s file and copies to the M.D./Ph.D. office. Continued participation in the Neurobiology program is subject to the satisfactory completion of requirements in a timely fashion. If any question arises about the satisfactory progress of a student, and the qualifying examination committee or the thesis committee cannot agree on an appropriate resolution, then the Neurobiology faculty will meet to determine a course of action.

Master’s Degrees

M.Phil. See Degree Requirements. Awarded only to students who are continuing for the Ph.D. degree. Students are not admitted for this degree.
M.S. Awarded only to students who are not continuing for the Ph.D. degree but who have successfully completed one year of the doctoral program (i.e., passing of at least four courses, including two Honors grades, and two successful laboratory rotations). Students are not admitted for this degree.

Program materials are available upon request to the Director of Graduate Studies, Department of Neurobiology, Yale University, PO Box 208001, New Haven CT 06520-8001.

Courses

NBIO 500b, Structural and Functional Organization of the Human Nervous System. Michael Schwartz, Pasko Rakic, and staff.
An integrative overview of the structure and function of the human brain as it pertains to major neurological and psychiatric disorders. Neuroanatomy, neurophysiology, and clinical correlations are interrelated to provide essential background in the neurosciences. Lectures in neurocytology and neuroanatomy survey neuronal organization in the human brain, with emphasis on long fiber tracts related to clinical neurology. Weekly three-hour laboratory sessions devoted to neuroanatomy in which students dissect the human brain and examine histological sections in close collaboration with faculty members. Lectures in neurophysiology cover various aspects of neural function at the cellular level, with a strong emphasis on the mammalian nervous system. Each student may participate in a weekly physiology conference with a faculty member, covering such topics as vision, sensory physiology, motor systems, simple nervous systems, or general neurophysiology. Clinical correlations consist of five sessions given by one or two faculty members representing both basic and clinical sciences. These sessions relate neurological symptoms to cellular processes in various diseases of the brain. Variable class schedule; contact course instructors. Also NSCI 510b.

NBIO 501a, Principles of Neuroscience. Marina Picciotto, Mark Yeckel.
WF 3.15–4.45
General neuroscience seminar: lectures, readings, and discussion of selected topics in neuroscience. Emphasis is on how approaches at the molecular, cellular, physiological, and organismal levels can lead to understanding of neuronal and brain function. Also NSCI 501a.

NBIO 502a, Structure and Function of Neocortex. Neurobiology Faculty.
This course covers anatomical, biochemical, and physiological organization of selected sensory, motor, and association regions of cortex. Sample topics discussed include development, evolution of multiple representations, columnar organization, and plasticity of neocortex. Permission of instructor required.

NBIO 507b, Cellular and Molecular Mechanisms of Neurological Disease. Dhasakumar Navaratnam, Stephen Strittmatter, Stephen Waxman.
TTh 4–5
Focuses on those diseases (Alzheimer’s, Parkinson’s, ALS, and other neurodegenerative diseases, Triplet Repeat induced diseases, multiple sclerosis, epilepsy, etc.) in which modern neuroscience has advanced mechanistic explanations for clinical conditions. The course highlights recent molecular, electrophysiological, and imaging experiments in parsing disease mechanisms. The application of pathophysiologic understanding to therapeutics is considered. Web casts of the lectures and Internet-based interactive tutorials are also available. The course extends a twelve-lecture course, Neurobiologic Mechanisms of Disease, offered in the spring of 2007. The course can be taken for credit or audited. Those wishing credit will be graded on a 30-minute Internet-based final exam and a term paper. Also NSCI 507b.

NBIO 509b, Synaptic Organization of the Nervous System. Gordon Shepherd, Anne Williamson, Michael Hines.
An integrative introduction to the principles underlying the organization of neural systems. The focus is on the best-understood systems, including spinal cord, olfactory bulb, retina, cerebellum, thalamus, basal ganglia, and cerebral cortex. Students integrate experimental findings from anatomy, electrophysiology, and neuropharmacology with computational models at the cellular and circuit level to understand the neural basis of behavior. Also NSCI 539b.

NBIO 510, Introduction to Methods in Cellular and Molecular Neurobiology. Neurobiology Faculty.
Firsthand insight into various techniques and approaches used in neuroscience. Light microscopic techniques include various metallic impregnation methods, autoradiography, anterograde and retrograde axonal transport methods, hybridoma and recombined DNA technology, deoxyglucose metabolic method, fluorescent and immunocytochemical methods. Electron microscopy encompasses transmission, electronmicroscopic autoradiography, and immuno-peroxidase methodology. Choice of techniques and hours to be arranged with individual faculty or staff members of the Department of Neurobiology.

NBIO 511, Introduction to Techniques Used in Electrophysiological Analysis at the Cellular Level. Neurobiology Faculty.
Includes practical training in in vivo and in vitro nervous system preparations, extracellular and intracellular recordings, sensory stimulation, dye injections, and selected neuropharmacological procedures. Choice of techniques and hours to be arranged with individual faculty of the Department of Neurobiology.

[NBIO 524b, Neurodevelopment and Neuropsychiatric Disorders.]

[NBIO 535b, History of Modern Neuroscience.]

[NBIO 570a, Cellular and Network Dynamics of Sensory and Motor Functions.]

[NBIO 590a, Sensory Neuroethology: Bats and Owls, Electric Fish, and Beyond.]

NBIO 602, Topics in Cortical Development and Evolution. Pasko Rakic.
This advanced tutorial course involves extensive reading, discussion, and pilot experiments on the topic.

NBIO 610b, Fundamentals in Neurophysiology. Vincent Pieribone, Fred Sigworth.
This course is designed for students who wish to gain a theoretical and practical knowledge of modern neurophysiology. Graduate students specializing in neurophysiology and non-neurophysiology are encouraged to attend, as the course begins at a very basic level and progresses to more complicated topics. Topics include properties of ion channels, firing properties of neurons, synaptic transmission, and neurophysiology methodology.

NBIO 720a, Neurobiology. Haig Keshishian, Paul Forscher.
MWF 11.30–12.20
Examination of the excitability of the nerve cell membrane provides a starting point for the study of molecular, cellular, and intracellular mechanisms underlying the generation and control of behavior. Also MCDB 720a^u, NSCI 720a.

Next: Neuroscience