The GABAA receptor is a critical part of the sensing machinery that triggers homeostatic plasticity of synaptic strength and intrinsic excitability

Generating and maintaining stability is a problem that neural networks must manage during development. Whereas Hebbian forms of plasticity allow for fast experience-dependent modification of synapses, these changes in synaptic strength can lead to the destabilization of neuronal firing rates if long-term potentiation and long-term depression are unconstrained. A new set of mechanisms, termed homeostatic plasticity, aids in the stabilization of network spiking activity by restraining the average amount of spiking activity within a cell or a network of cells within a set range. Experimentally homeostatic plasticity has been examined by pushing spiking activity to extremes; either all activity is blocked or activity is highly enhanced. Studies in multiple experimental systems have found that chronically reducing spiking activity in synaptically connected neurons triggers coordinated increases in excitatory synaptic strength as well as increases in intrinsic cellular excitability. These changes are thought to be homeostatic as they act to increase activity to recover normal levels. The mechanisms by which cells monitor spiking activity and trigger compensatory changes in synaptic strength are not well understood. Cells could monitor the average level of membrane depolarization or the activation of neurotransmitter receptors as a proxy for activity. Few studies have been able to separate the roles of membrane depolarization and neurotransmission. However, using the developing chick embryonic spinal cord, we are able to block either excitatory GABAAergic or glutamatergic transmission without significantly altering membrane depolarization. We found that blocking GABAA receptors, but not glutamate receptors, triggered compensatory increases in synaptic strength and cellular excitability similar to those demonstrated after activity block. This suggests a special role for the GABAA receptor as a critical part of the machinery that senses changes in activity and triggers compensatory mechanisms.