Mechanisms of Synaptic Transmission and Plasticity

The general questions that motivate our research 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 their properties in neurons from mammalian brains using biophysical, cell biological and molecular methods.

A major effort is directed towards understanding presynaptic mechanisms, in particular the regulation of vesicle pools and their traffic. We use synthetic dyes as well as genetically encoded fluorescent probes to label synaptic components and use high-resolution fluorescence microscopy to image synapses in living cells. The structure, function and plasticity of identified synapses are then studied over periods of minutes to hours. To study synapses at high resolution in intact preparations such as brain slices, we develop and use novel methods including multi-photon microscopy.

A second area of research addresses the mechanisms in long-term synaptic plasticity. We use molecular biological tools to alter activity in individual neurons and examine the consequences of this alteration on synaptic strength. For example, we have found that suppressing activity of single neurons by overexpressing potassium channels can reduce the synaptic input to the suppressed neuron. The experimental preparations for these studies are brain slices and primary neuronal cultures, and tools will be selected from molecular biology, electrophysiology and optical microscopy. Some of these methods are also being adapted for use in the intact brain.

Selected Publications:

Star, E.N., Kwiatkowski, D.J. and Murthy, V.N. (2002). Rapid turnover of actin in dendritic spines and its regulation by activity. Nature Neuroscience, 5:239-246.

Murthy, V.N., Schikorski, T. Stevens, C.F. & Zhu, Y. (2001). Inactivity produces increase in transmitter release and synapse size. Neuron 32:673-682.

Li, Z. and Murthy, V.N. (2001). Visualizing post-endocytic traffic of synaptic vesicles at hippocampal synapses. Neuron 31:593-605.

Murthy, V.N. (1999). Optical detection of synaptic vesicle exocytosis and endocytosis. Current Opinion in Neurobiology 9:314-320.

Murthy, V.N. and Stevens, C.F. (1998). Synaptic vesicles retain their identity through the endocytic cycle. Nature 392, 497-501.