Homeostatic regulation of glutamate release in response to depolarization

Proper nervous system function requires a balance between excitation and inhibition. Systems of homeostasis may have evolved in neurons to help maintain or restore balance between excitation and inhibition, presumably because excessive excitation can cause dysfunction and cell death. This article reviews evidence for homeostatic mechanisms within the hippocampus that lead to differential regulation of glutamate and γ-aminobutyric acid release in response to conditions of excess depolarization. We recently found differential effects on glutamate release at the level of action potential coupling to transmitter release, vesicular release probability, and vesicle availability. Such differential regulation may help to prevent excitotoxicity and runaway excitation.