Title

Compensatory Changes in Cellular Excitability, Not Synaptic Scaling, Contribute to Homeostatic Recovery of Embryonic Network Activity

Document Type

Article

Publication Date

4-21-2009

Abstract

When neuronal activity is reduced over a period of days, compensatory changes in synaptic strength and/or cellular excitability are triggered, which are thought to act in a manner to homeostatically recover normal activity levels. The time course over which changes in homeostatic synaptic strength and cellular excitability occur are not clear. Although many studies show that 1–2 days of activity block are necessary to trigger increases in excitatory quantal strength, few studies have been able to examine whether these mechanisms actually underlie recovery of network activity. Here, we examine the mechanisms underlying recovery of embryonic motor activity following block of either excitatory GABAergic or glutamatergic inputs in vivo. We find that GABAA receptor blockade triggers fast changes in cellular excitability that occur during the recovery of activity but before changes in synaptic scaling. This increase in cellular excitability is mediated in part by an increase in sodium currents and a reduction in the fast-inactivating and calcium-activated potassium currents. These findings suggest that compensatory changes in cellular excitability, rather than synaptic scaling, contribute to activity recovery. Further, we find a special role for the GABAA receptor in triggering several homeostatic mechanisms after activity perturbations, including changes in cellular excitability and GABAergic and AMPAergic synaptic strength. The temporal difference in expression of homeostatic changes in cellular excitability and synaptic strength suggests that there are multiple mechanisms and pathways engaged to regulate network activity, and that each may have temporally distinct functions.

DOI

10.1073/pnas.0813058106