Presynaptic ionotropic GABA receptors a homeostatic feedback mechanism at axon terminals of inhibitory interneurons

Abstract

Conclusions: Presynaptic autoreceptors modulate the release of GABA from terminals of inhibitory interneurons. We have shown that in rodent hippocampal CA3 this feedback involves the activation of ionotropic GABAAR which suppress further release in acutely prepared tissue. Under conditions of different EC1, the same feedback might be positively coupled to release, giving rise to bursts of IPSCs after an initial (large) event. Our further experimental and theoretical studies show that presynaptic ionotropic GABAAR are specifically important during one mechanism of inhibitory synaptic plasticity, namely changes in GABA metabolism. Besides alterations of the amount of released GABA this homeostatic mechanism induces changes in the frequency of vesicle release which are likely to be mediated by presynaptic ionotropic GABAAR. This new feedback mechanism will be important to understand the dynamics of inibitory synaptic signaling and the ratio between tonic and phasic GABAergic inhibition.