D(2)-like Dopamine Receptors Differentially Regulate Unitary IPSCs Depending on Presynaptic GABAergic Neuron Subtypes in Rat Nucleus Accumbens Shell

J Neurophysiol. 2012 Jan;107(2):692-703. doi: 10.1152/jn.00281.2011. Epub 2011 Nov 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Atropine / pharmacology
  • Bicuculline / pharmacology
  • Biophysics
  • Dopamine Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electric Stimulation
  • Female
  • GABA-A Receptor Antagonists
  • GABAergic Neurons / classification
  • GABAergic Neurons / cytology*
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials / physiology*
  • Male
  • Muscarinic Antagonists / pharmacology
  • Neural Pathways / physiology
  • Nucleus Accumbens / cytology*
  • Patch-Clamp Techniques
  • Presynaptic Terminals / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / physiology*
  • Time Factors

Substances

  • Dopamine Agents
  • GABA-A Receptor Antagonists
  • Muscarinic Antagonists
  • Receptors, Dopamine D2
  • Atropine
  • Bicuculline