Dopamine and cyclic-AMP regulated phosphoprotein-32-dependent modulation of prefrontal cortical input and intercellular coupling in mouse accumbens spiny and aspiny neurons.
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.
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000172:deficiency / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000166:cytology*; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000502:physiology* / Q000528:radiation effects; D019257:Quinpirole / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects
D018491:Dopamine Agonists; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D018756:GABA Antagonists; C497929:Ppp1r1b protein, mouse; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C013411:biocytin; D008239:Lysine; D004298:Dopamine; D001640:Bicuculline