CAREER: Long-Term Changes in Synaptic Function Induced by Selective Suppression of Activity in Single Neurons

Harvard University, Cambridge MA

Investigators

Abstract

Lay abstract CAREER: Long-term changes in synaptic function induced by selective suppression of activity in single neurons The adaptation of the brain to environmental changes is achieved in part through modifications in the strength of synapses, which are specialized connections between neurons. The precise rules governing synapse formation, maturation and subsequent modification in the central nervous system are not fully understood. Using electrophysiology, fluorescence microscopy and molecular biological tools, Dr. Murthy will investigate long-term modification of identified synapses in a simple neural network in vitro. The overall research objectives of the proposal are (i) to determine the consequences of selective, long-term reduction of activity in a single neuron within an active network, and (ii) to understand the locus and mechanisms in synaptic modification resulting from this manipulation. Two general classes of results might be anticipated - homeostatic modifications that allow neuron-wide increase in synaptic strength that will restore the overall activity of the 'quiet' cell to normal levels, and competitive modifications that reduce or eliminate synaptic input and output of the 'quiet' cell. This experimental system will offer unparalleled access to detailed cell biological investigations of synaptic modification - from the level of gene expression to physiological analysis at single synapse resolution. The investigator will also integrate education with his research program by developing up-to-date instructional material for an advanced course in neuronal cell biology. Since optical microscopy has become an indispensable tool in cellular-level research, Dr. Murthy will organize short departmental workshops on advanced imaging techniques. In addition to these instructional elements, the investigator will also mentor undergraduate and graduate students, including those from underrepresented groups.