Ambient GABA modulates septo-hippocampal inhibitory terminals via presynaptic GABAb receptors

- The magnitude of septo-hippocampal GABAergic inhibition on hippocampal interneurons is constrained by GABAb receptors.
- GABAbR activation decreases GABA release from SH-GABA terminals while deactivation increases it.
- Perisomatic targeting interneurons receive larger septal inhibition compared to the dendrite targeting interneurons.
- Tonic GABAbR mediated tone on SH-GABA terminals is regulated by the ambient GABA concentration.

The septo-hippocampal GABAergic pathway connects inhibitory neurons in the medial septum with hippocampal interneurons. Phasic release of GABA from septo-hippocampal terminals is thought to play an important role in shaping hippocampal network activity during behavior. Here, we found that GABA release from septo-hippocampal terminals is under negative feedback from the hippocampal local inhibitory network. We found that the strength of septo-hippocampal GABAergic inhibition is constrained by presynaptic GABAb receptors that are activated by ambient GABA during states of increased hippocampal network activity.This article is part of the Special Issue entitled 'GABAergic Signaling in Health and Disease'.