GABA<SUB>B </SUB>RECEPTOR-MEDIATED EFFECTS IN VIP-EXPRESSING INTERNEURONS OF THE DENTATE GYRUS

The dentate gyrus (DG) acts as a gateway to the hippocampus, processing multi-modal information arriving from neocortical areas via the entorhinal cortex. In its netwotk, principal neurons, the granule cells (GCs), interact with a morphologically, physiologically, and neurochemically hetergogenous population of inhibitory GABAergic interneurons (INs). Among various IN types, vasoactive intestinal peptide-expressing (VIP) INs are known to selectively target other INs and thereby directly modulate the GABAergic system.
GABA acts in addition to ionotropic GABAA via metabotropic GABAB receptors. GABAB receptors mediate diverse effects in cortical networks and are particularly highly expressed in INs, however their action in VIP-INs has not been studied.
Therefore. to elucidate the function of GABA_B receptors (GABA_BRs) in the regulation of the electrical activity of DG VIP INs, the effects of GABA_BR agonist and antagonist on VIP INs were investigated in VIP/tdTomato mouse slices by whole-cell patch-clamp recordings. VIP INs display various input resistances, ranging from 130 MΩ to 1.5 GΩ, and different discharge patterns, including regularly spiking, fast-adapting, and irregularly firing phenotypes. Bath application of the agonist baclofen (10 μM) -induced a hyperpolarization and reduced excitability of VIP INs. This effect was underlied by an outward whole-cell current of 40 ± 10.2 pA in DG VIP INs which was fully reversed buy the application of the agonist CGP (5 μM). These results suggest that postsynaptic GABA_BRs are highly expressed and modulate the activity of VIP INs of the DG.