D1/D5 dopamine receptors support postsynaptic long-term GABAergic synaptic plasticity in the hippocampus

It is well known that dopamine is a significant player in regulation of various forms of glutamatergic synaptic plasticity. In particular, activation of D1/D5 dopamine receptors was shown to increase the magnitude of hippocampal excitatory long-term potentiation (LTP) (Hansen and Manahan-Vaughan, 2014). We have also demonstrated that D1/D5 dopamine receptors supports NMDA-dependent LTP selectively in st. oriens of the CA1 region (Brzdak et al., 2019). While involvement of dopamine receptors, especially D1/D5, in the excitatory plasticity is well established, their role in the GABAergic plasticity remains unknown. To address this issue, we measured mIPSCs using patch-clamp recordings in acute slices from SST-tdTomato mice and we used a protocol that evokes inhibitory long-term potentiation (iLTP) by applying 20 µm NMDA for 3 min (Brzdak, Lebida et al., 2023). To check the role of D1/D5 dopamine receptors in this type of iLTP we used D1/D5 dopamine receptors inhibitor (SCH 23390). We observed that, in the presence of SCH 23390, mIPSCs amplitude measured from SST interneurons was significantly potentiated (mIPSC amplitude relative to baseline: 110±4%, n = 5). Moreover, bath application of SCH 23390 led to impairment of NMDAR-dependent iLTP with conversion to iLTD (SCH: 86±3%; n=6; CTR: 127±4%; p<0.001). In the current study we demonstrated that pharmacological manipulations of D1/D5 dopamine receptors play a crucial role in GABAergic synaptic plasticity.Supported by National Science Centre (Poland) grants OPUS 2021/43/B/NZ4/01675, SONATINA 2023/48/C/NZ4/00072, MINIATURA 2023/07/X/NZ4/00687