Dopamine and cyclic-AMP regulated phosphoprotein-32-dependent modulation of prefrontal cortical input and intercellular coupling in mouse accumbens spiny and aspiny neurons

S. P. Onn, M. Lin, J. J. Liu, A. A. Grace

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The roles of dopamine and cyclic-AMP regulated phosphoprotein-32 (DARPP-32) in mediating dopamine (DA)-dependent modulation of corticoaccumbens transmission and intercellular coupling were examined in mouse accumbens (NAC) neurons by both intracellular sharp electrode and whole cell recordings. In wild-type (WT) mice bath application of the D2-like agonist quinpirole resulted in 73% coupling incidence in NAC spiny neurons, compared with baseline (9%), whereas quinpirole failed to affect the basal coupling (24%) in slices from DARPP-32 knockout (KO) mice. Thus, D2 stimulation attenuated DARPP-32-mediated suppression of coupling in WT spiny neurons, but this modulation was absent in KO mice. Further, whole cell recordings revealed that quinpirole reversibly decreased the amplitude of cortical-evoked excitatory postsynaptic potentials (EPSPs) in spiny neurons of WT mice, but this reduction was markedly attenuated in KO mice. Bath application of the D1/D5 agonist SKF 38393 did not alter evoked EPSP amplitude in WT or KO spiny neurons. Therefore, DA D2 receptor regulation of both cortical synaptic (chemical) and local non-synaptic (dye coupling) communications in NAC spiny neurons is critically dependent on intracellular DARPP-32 cascades. Conversely, in fast-spiking interneurons, blockade of D1/D5 receptors produced a substantial decrease in EPSP amplitude in WT, but not in KO mice. Lastly, in putative cholinergic interneurons, cortical-evoked disynaptic inhibitory potentials (IPSPs) were attenuated by D2-like receptor stimulation in WT but not KO slices. These data indicate that DARPP-32 plays a central role in 1) modulating intercellular coupling, 2) cortical excitatory drive of spiny and aspiny GABAergic neurons, and 3) local feedforward inhibitory drive of cholinergic-like interneurons within accumbens circuits.

Original languageEnglish (US)
Pages (from-to)802-816
Number of pages15
JournalNeuroscience
Volume151
Issue number3
DOIs
StatePublished - Feb 6 2008

Keywords

  • DA D1 and D2 receptor
  • excitatory and inhibitory synaptic transmission
  • mouse accumbens neurons
  • non-synaptic gap junction-mediated morphological coupling
  • sharp-electrode recording
  • whole cell recording

ASJC Scopus subject areas

  • Neuroscience(all)

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