Critical period in visual cortex: inhibitory circuits

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18. GOALS FOR FELLOWSHIP TRAINING AND CAREER INSTITUTION/COMPANY SUPERVISOPJEMPLOYER Gettysburg College Spring-Ford Dist. Pheonixville Dist. Northeastern University Dr Frederick C Davis Northeastern University Dr Frederick C Davis University of Kentucky Dr Douglas G McMahon I am fascinated by how sensory experiences form and refine the circuitry of the central nervous system that is used to code externally-driven neuronal activity. Intellectually, this training plan will enhance my ability to formulate testable hypotheses regarding the cellular mechanisms that drive the plasticity underlying behaviorally relevant sensory processing. Technically, I will receive training in 2-photon imaging and analysis useful for real-time imaging at high resolution in living tissue. I will receive training in mouse genetics using bacterial artificial chromosome technology to target specific cell types for physiological study and in vivo manipulation. These skills will enable me to succeed in my career goal of becoming an independent research scientist and train students of all levels in neurobiology. Future studies will examine the impact of light or other sensory stimulation on shaping on-going gene expression dynamics and neuronal activity in the context of developmental and behavioral states. The long-term goal is to more precisely define the cellular basis of how organisms adapt to their environment, and how to intervene when internal circuits are not well adapted. -li'll[-1"]i 19. NAME AND DEGREE(S) Z. Josh Huang 20. POSITION/RANK Assistant Professor 21. RESEARCH INTERESTS/AREAS experience-d _ependent p]astJcity neurotrophins mouse _enetics 22.DES RcIPeTIOntrI.DsosnuotmexnceedusraoceGpreov,nids%cde)understhaonwdexperiesnhcaepbersaifnunctioRn.ecesnttudiiensvisual cortex suggest that the maturation of intracortical inhibitory circuits is necessary to initiate and drive ocular dominance plasticity during the critical period. However, the maturation and regulation of the specific type of inhibitory circuit involved is not understood. Critical period plasticity is also modulated by visual deprivation and BDNF over-expression, although the cellular mechanisms remain unknown. Here we hypothesize that the functional maturation of a specific subtype of GABAergic neurons, parvalbumin (Pv) basket interneurons, are a component of the inhibitory mechanism underlying critical period platicity, and a cellular target of experience deprivation and BDNF regulation. Using bacterial artificial chromosome transgenic (BAC) mice expressing GFP in Pv-interneurons, we will characterize the morphological and physiological development of Pv-interneurons using two photon laser scanning microscopy and electrophysiology in brain slices. We will then examine the effects of dark rearing on the maturation of Pv-interneurons. Finally, we will test the role of BDNF in experience-dependent maturation of Pv-interneurons by blocking trkB signaling using BAC transgenic mice expressing a dominant negative form of trkB receptor specifically in Pv-interneurons. These results will reveal a mechanism by which experience shapes function of an identified inhibitory network and provide strong evidence that maturation of the Pv-interneuron circuit facilitates the coding of visual information necessary to drive ocular dominance plasticity. The knowledge gained will aid in the design of drug treatments in diseased states such as epilepsy and schizophrenia. PHS 416-1 (Rev. 12/98) Form Page 2 BB cc Table of Contents ========================================Section End===========================================