Visualizing activity-dependent changes in synaptic connectivity

Venkatesh Murthy
Harvard University

Abstract

Modification of synapses by activity is at the heart of most ideas about how the brain adapts to environmental changes. Many forms of synaptic plasticity, lasting from milliseconds to days have been identified and studied in mammalian brains. Long-term consequences of altering activity are typically studied by manipulating populations of neurons in unison [1]. To determine specific cellular mechanisms and rules of synaptic modification, however, it may be necessary to perturb selectively the properties of individual neurons. We have developed a method to suppress electrical activity chronically in single neurons and simultaneously visualize the morphology and connectivity of the neuron. Using this method in a simple experimental preparation, we have found that multiple forms of synaptic plasticity can be triggered by suppression of activity [2]. These studies are aided by novel genetically-encoded fluorescent probes [3] that can be used to assess functional properties of individual presynaptic terminals and determine how these properties are altered by activity. The methods developed in reduced preparations and the results obtained from them prompt future experiments in the intact brain.

1. Burrone, J. and Murthy, V.N. 2003. Homeostasis and synaptic gain control. Curr. Opin. Neurobiol. (in press)

2. Burrone, J., O'Byrne, M. and Murthy, V.N. 2002. Multiple forms of synaptic plasticity triggered by selective suppression of activity in single neurons. Nature 420:414-418.

3. Miesenbock, G., De Angelis, D. A., and Rothman, J. E. 1998. Visualizing secretion and synaptic transmission with pH-sensitive green fluorescence proteins. Nature 394, 192-195.

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