D(2)-like dopamine receptors differentially regulate unitary IPSCs depending on presynaptic GABAergic neuron subtypes in rat nucleus accumbens shell.

In the nucleus accumbens (NAc), a medium spiny (MS) neuron receives GABAergic inputs from two major sources: fast-spiking (FS) neurons and other, adjacent MS neurons. These two types of inhibitory synapses are considered to play different roles in output activities, i.e., FS→MS connections suppress output from the NAc whereas MS→MS connections contribute to lateral inhibition. In the present study, we focused on the electrophysiological properties of unitary inhibitory postsynaptic currents (uIPSCs) obtained from MS→MS connections and FS→MS connections and examined the effects of quinpirole, a dopamine D(2)-like receptor agonist, on uIPSCs with multiple whole cell patch-clamp recording. Application of quinpirole (1 μM) reliably suppressed the amplitude of uIPSCs by 29.6% in MS→MS connections, with increases in paired-pulse ratio and failure rate. The suppressive effects of quinpirole on uIPSCs were mimicked by 1 μM PD128907, a D(2/3) receptor agonist, whereas quinpirole-induced suppression of uISPCs was blocked by preapplication of 1 μM sulpiride or 10 μM nafadotride, both D(2/3) receptor antagonists. On the other hand, quinpirole (1 μM) had divergent effects on FS→MS connections, i.e., quinpirole increased uIPSC amplitude in 38.1% of FS→MS connections and 23.8% of FS→MS connections were suppressed by quinpirole. Analysis of coefficient of variation in uIPSC amplitude implied the involvement of presynaptic mechanisms in quinpirole-induced effects on uIPSCs. These results suggest that activation of D(2)-like receptors facilitates outputs from MS neurons in the NAc by reducing lateral inhibition during a dormant period of FS neuron activities.