D1-type dopamine receptors are critical for GABAergic synaptic plasticity in CA1 mouse hippocampal SST interneurons and pyramidal cells

Dopamine modulates brain functions such as memory and learning, and studies into underlying mechanisms have been largely focused on glutamatergic synapses and their plasticity. Much less is known about the dopaminergic modulation of inhibitory plasticity at synapses formed by distinct GABAergic interneurons targeting different cells. Herein, we addressed the role of D1-type dopamine receptors (D1Rs) in inhibitory plasticity at synapses between interneurons (INs) and pyramidal cells (PCs), as well as between INs in the CA1 region. Activation and blockade of D1Rs increased and reduced the mIPSCs amplitude (measured from PCs), respectively, while the decay kinetics was prolonged, indicating a complex postsynaptic mechanism. We also checked the D1Rs effect on heterosynaptic NMDA-induced inhibitory long-term potentiation (iLTP) measured at PCs and found that blockade of D1Rs converted iLTP into inhibitory long-term depression (iLTD), whereas D1Rs activation slightly diminished iLTP. NMDA-induced iLTP in synapses formed by parvalbumin- (PV) positive INs on PCs was reduced to zero by SKF, while SCH converted iLTP to iLTD. Interestingly, NMDA-induced iLTP in the somatostatin- (SST) positive INs was reversed to iLTD by both SKF and SCH, while these compounds were ineffective on baseline activity, and these effects were mirrored by changes in gephyrin clusters. Thus, the impact of D1Rs on inhibitory plasticity observed at the SST INs and PCs showed differences with respect to baseline activity, NMDA-induced plasticity, and the kinetics of synaptic currents. Altogether, we show that D1Rs modulate inhibitory long-term plasticity in a manner dependent on the presynaptic and target neurons.