Dopamine D2-like receptors differentially shape GABAergic plasticity in distinct subtypes of hippocampal VIP interneurons

Abstract

Abstract Dopamine regulates diverse brain functions, including learning and memory, primarily through two receptor types, D1R and D2R, which activate and inhibit adenylate cyclase, respectively. Dopaminergic system critically modulates glutamatergic transmission, but less is known about its impact on GABAergic plasticity, in which the role of the D2R remains practically unexplored. Vasoactive intestinal polypeptide-expressing (VIP) interneurons (INs) represent an important subset, comprising those innervating other inhibitory cells, mediating disinhibition, and others contacting various neurons, including pyramidal cells. Herein, we addressed the role of D2Rs in GABAergic plasticity in two classes of VIP INs: interneuron-specific (IS) and non-interneuron specific (non-IS). We show that D2Rs activation with quinpirole upregulated the amplitude of miniature inhibitory postsynaptic currents (mIPSCs) in IS, while analogous result was observed in non-IS VIP INs upon D2Rs blockade with sulpiride and these effects were accompanied by prolongation of mIPSC decay. Brief NMDA application, known to evoke heterosynaptic inhibitory long-term plasticity, induced inhibitory LTP (iLTP) at GABAergic synapses onto IS VIP INs and iLTD in non-IS VIP INs. Notably, D2R agonism, but not antagonism, impaired NMDA-evoked iLTP in IS VIP INs, consistent with occlusion. Collectively, these findings reveal cell-specific and D2R-dependent GABAergic plasticity phenomena in IS and non-IS VIP INs.