1. Department of Molecular & Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA

Correspondence to: Venkatesh N. Murthy Correspondence and requests for materials should be addressed to V.N.M. (e-mail: Email: vnmurthy@fas.harvard.edu).

Abstract

The rules by which neuronal activity causes long-term modification of synapses in the central nervous system are not fully understood. Whereas competitive or correlation-based rules result in local modification of synapses, homeostatic modifications allow neuron-wide changes in synaptic strength, promoting stability^{1, 2}. Experimental investigations of these rules at central nervous system synapses have relied generally on manipulating activity in populations of neurons^{1, 3, 4, 5, 6}. Here, we investigated the effect of suppressing excitability in single neurons within a network of active hippocampal neurons by overexpressing an inward-rectifier potassium channel. Reducing activity in a neuron before synapse formation leads to a reduction in functional synaptic inputs to that neuron; no such reduction was observed when activity of all neurons was uniformly suppressed. In contrast, suppressing activity in a single neuron after synapses are established results in a homeostatic increase in synaptic input, which restores the activity of the neuron to control levels. Our results highlight the differences between global and selective suppression of activity, as well as those between early and late manipulation of activity.