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>