D2-like dopamine receptors differentially regulate unitary IPSCs depending on presynaptic GABAergic neuron subtypes in rat nucleus accumbens shell

Kohnomi S, Koshikawa N, Kobayashi M. D-2-like dopamine receptors differentially regulate unitary IPSCs depending on presynaptic GABAergic neuron subtypes in rat nucleus accumbens shell. J Neurophysiol 107: 692-703, 2012. First published November 2, 2011; doi:10.1152/jn.00281.2011.-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 mu M) 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 mu M PD128907, a D-2/3 receptor agonist, whereas quinpirole-induced suppression of uISPCs was blocked by preapplication of 1 mu M sulpiride or 10 mu M nafadotride, both D-2/3 receptor antagonists. On the other hand, quinpirole (1 mu M) 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.