Venkatesh Murthy

Assistant Professor
Molecular and Cellular Biology
Harvard University
16 Divinity Avenue
Cambridge, MA 02138
Ph: (617) 496-4833
FAX: (617) 495-9300
Email: vnmurthy@fas.harvard.edu

My home page at Harvard University.

Scientific Interests

The general questions that motivate research in my lab are: how do neurons in the brain communicate with each other, and how does learning modify this communication? Since the efficacy of information transfer between neurons is governed by the fundamental properties of synapses, we study these properties in neurons from mammalian central nervous system using biophysical, cell biological and molecular methods. Three general areas of research will guide experiments:

Steps in transmitter release at synapses : The elementary steps in synaptic transmission include the release of neurotransmitter from synaptic vesicles by action potentials, and the activation of postsynaptic receptors and signaling cascades. Work in our lab focusses on the regulation of transmitter release. We use a combination of cell biological, biophysical, and fluorescence imaging methods to follow the life history of individual synaptic vesicles from endocytosis, through recycling steps, to exocytosis. Ultimately, we aim to relate the different steps in vesicle trafficking to the underlying molecular interactions. The model system for this project is primary cultures of hippocampal neurons from rodents. Synaptic function can be assayed at high resolution in this preparation through electrophysiological and optical methods. For example, single synaptic events can be detected reliably at visualized individual synapses, allowing a comprehensive characterization of single synapse properties.

Modification of synaptic efficacy: The adaptation of the brain to environmental changes is achieved in part through modifications in synaptic efficacy. We study the mechanisms involved in synaptic plasticity in hippocampal neurons using primary cultures. Two general questions will guide specific experiments: (a) what parameters of synaptic function are altered, and (b) what gene products are involved in these alterations? Preliminary work using primary cultures indicates that synaptic properties can be dramatically altered by persistent changes in levels of activity over a period of a day or two. This preparation will be a useful model system for studying the molecular basis for functional changes in synaptic properties at specific visualized synapses. Experimental tools will be selected from molecular biology, electrophysiology and optical microscopy.

Synaptic function in vivo: An issue of general interest in neurobiology is the connection between molecular/cellular properties of neurons, and the behavior of an organism. We are particularly interested in studying synaptic function in the living brain using electrophysiological methods and optical imaging at the level of individual synapses. Novel genetically encoded fluorescent probes that can report synaptic function (for example, GFP fusions with synaptic vesicle proteins) will be developed and tested in brain slices. Then, we will extend this method to the rodent olfactory system.