Jane M. Sullivan - US grants

DESCRIPTION: (Applicant's Abstract) Marijuana is one of the most widely used drugs of abuse in the world, and it is the goal of this proposal to understand the neurobiological basis for its effects on synaptic function. Marijuana and its constituent cannabinoids have been shown to have analgesic, antiemetic and antiglaucoma properties, but the psychoactive side effects of these drugs - most notably, cognition and memory impairments - make them undesirable as therapeutic agents. These detrimental effects are likely to be mediated, at least in part, by alteration of the normal synaptic functioning of the hippocampus, a brain region that plays a central role in certain forms of learning and memory. This proposal describes a series of experiments to determine the cellular and molecular basis for the effects of cannabinoids on hippocampal synaptic function. Using electrophysiological techniques, the acute and chronic effects of cannabinoids on four aspects of basic synaptic function, and on four forms of synaptic plasticity - some of which are believed to form the cellular basis for learning and memory - will be determined. Using a pharmacological approach, the role of calcium and potassium channel modulation in cannabinoid-mediated effects will be determined. Using a combination of pharmacological and molecular biological approaches, the roles of different classes of G-proteins in cannabinoid-mediated effects will be determined. Understanding the cellular and molecular basis for the effects of cannabinoids on cognition and memory is a necessary first step in the rational design of selective therapeutic agents that can replicate the beneficial properties of cannabinoids without their negative psychoactive side effects. The proposed studies enhance memory or reverse memory loss. Finally, understanding the neurobiological basis for the effects of cannabinoids may aid in drug abuse prevention and treatment.

? DESCRIPTION (provided by applicant): The Graduate Program in Neuroscience, established at the University of Washington in 1996, is large and strong, with 48 students and 141 faculty members from 27 departments and 4 partner institutions across the city of Seattle. Our goal is to train the best neuroscientists possible, fostered by inclusion of students from diverse and underrepresented backgrounds. We have exceptional breadth and depth of research interests, including neurodevelopment, neurodegeneration, addiction, ion channel physiology and pathology, systems neuroscience, and computational neuroscience. The breadth of our faculty allows us to provide interdisciplinary training drawing from a variety of techniques and approaches, including neuroanatomy, biochemistry, molecular biology, physiology, biophysics, pharmacology, in vivo brain imaging, computational modeling and behavior. In addition to a solid core of required and elective courses, students also receive instruction in other key areas of professional development on topics including grant writing, public speaking and bioethics. Faculty mentors and the Graduate Training Committee closely monitor student progress to ensure that each student receives the guidance he or she needs to succeed. Graduates emerge from the program prepared to conduct independent research and equipped to pursue a variety of career paths. The intent of this proposal is to partially replace an Institutional Training Gran for Neurobiology (T32 GM007108) that the University of Washington has held for 40 years. T32 GM0007108 has been a crucial underpinning of our interdisciplinary Neuroscience PhD program, but is being retired because of administrative changes in the Institute of General Medical Sciences. The retiring award supported 12 students; here we seek support for 6. One of the primary attractions of our program is that it accommodates students with diverse academic backgrounds, and offers a wide selection of faculty with whom to work. This diversity of academic backgrounds, however, makes training grant support essential. It would be inappropriate to ask a faculty member to provide research support for a student whose background will not allow a fast track to productivity within that lab and on the specific research grant that will support the work. There are currently no other predoctoral training grants that are available to support early-stage students. Because the Graduate School funds our students in their first year, funds from this T32 would be used primarily to support students in their second year, when they are just beginning their dissertation research, and are still completing their elective coursework and teaching requirements. By supporting early-stage students while they remain substantially engaged in important components of their training outside their dissertation labs, this training grant will give our students greater independence and control at a critical stage of their graduate careers, and make a significant contribution to the continuing success of graduate training in neuroscience at the University of Washington.