INTRODUCTION: Dopaminergic neuromodulation is a crucial factor influencing cognitive functions and information processing in the hippocampus. Its role has been demonstrated in shaping the synaptic plasticity of excitatory synapses as well as in memory and learning processes (Tsetsenis et al., 2023). However, it is unknown if dopaminergic receptors could also modulate the inhibitory synaptic transmission and its long-term potentiation (iLTP) in different classes of interneurons (INs).

AIM(S): Herein, we examine the role of D2-family dopamine receptors (D2Rs) in modulating GABAergic synaptic transmission and its plasticity in two distinct groups of vasoactive intestinal peptide-expressing (VIP) INs.

METHOD(S): We performed patch-clamp recordings of miniature inhibitory postsynaptic currents (mIPSCs) in hippocampal brain slices from VIP-tdTomato mice, followed by anatomical analyses of VIP INs. To check the role of D2Rs in inhibitory transmission, we used D2R agonist (quinpirole) or antagonist (sulpiride). We also evoked iLTP by NMDA treatment in control conditions and after blocking or enhancing D2Rs activity.

RESULTS: We found that, in the presence of quinpirole, mIPSCs amplitude was significantly potentiated in type 3 interneuron-specific (IS3) VIP INs (118±4% of control) but not in basket cells (BC) VIP INs (94±7%). In contrast, application of sulpiride led to the opposite effects (IS3: 104±4%; BC: 116±5%). The amplitude increase was also coupled with a prolongation of mIPSCs duration (IS3+quinpirole: 129±9%; BC+sulpiryde: 118±7%). Furthermore, we discovered that exposure to NMDA induced iLTP in IS3 VIP INs (120±5%) and iLTD in BC VIP INs (78±3%). Moreover, in IS3 VIP INs iLTP was accompanied by prolonged mIPSCs decay (125±7%). Finally, this form of inhibitory plasticity was occluded by bath application of quinpirole (95±4%) indicating a key role of D2Rs.

CONCLUSIONS: Altogether, our results show that D2Rs signaling interferes with GABAergic transmission and plasticity in the hippocampus in cell-type specific manner.

FINANCIAL SUPPORT: Supported by the Polish National Science Center grants: OPUS 2021/43/B/NZ4/01675, SONATINA 2023/48/C/NZ4/00072, MINIATURA 2023/07/X/NZ4/00687.