D1-type dopamine receptors are critical for GABAergic synaptic plasticity

<p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:0.0001pt;text-align:justify;line-height:normal">Dopamine modulates key brain functions such as memory and learning; however, most studies have focused on glutamatergic synapses and their plasticity. In contrast, much less is known about the dopaminergic modulation of inhibitory plasticity at synapses formed by distinct GABAergic interneurons targeting different cells. Here, we investigated the role of D1-type dopamine receptors (D1Rs) in inhibitory plasticity at synapses between interneurons (INs) and pyramidal cells (PCs), as well as at synapses between INs in hippocampus. Activation and blockade of D1Rs increased and decreased the amplitude of mIPSCs recorded from PCs, respectively. In both cases, decay kinetics were prolonged, suggesting a complex postsynaptic mechanism. We also found that PV→PC and SST→PC synapses undergo inhibitory long-term depression (iLTD) following blockade of D1/D5 dopamine receptors. In contrast to the effects observed for mIPSCs, SKF did not enhance eIPSCs mediated by either PV- or SST-positive interneurons innervating PCs. Furthermore, we examined the influence of D1Rs on heterosynaptic NMDA-induced inhibitory long-term potentiation (iLTP) measured in PCs. Blockade of D1Rs converted iLTP in iLTD, whereas D1R activation slightly attenuated iLTP. Interestingly, NMDA-induced iLTP in SST INs was reversed to iLTD by both SKF and SCH. These effects were paralleled by corresponding changes in gephyrin cluster organization. Altogether, our results demonstrate that D1Rs modulate inhibitory long-term plasticity in a manner that depends on both the presynaptic interneuron type and the postsynaptic target neuron.</p>