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

Abstract

The roles of 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 wildtype (WT) mice bath application of the D2-like agonist quinpirole resulted in 73% coupling incidence in NAC spiny neurons, compared to 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 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 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 KeywordsExcitatory and inhibitory synaptic transmission; non-synaptic gap junction-mediated morphological coupling; DA D1 & D2 receptor; mouse accumbens neurons; whole cell recording; sharp-electrode recording Altered glutamate transmission from the prefrontal cortex (PFC) to the ventral striatum is often implicated in schizophrenia and drug addiction; disorders that involve dopamine (DA) dysfunctional states (Grace, 1991;2000;2001;Albert et al., 2002;Saal et al., 2003). DA acting on D2-like receptors present on prefrontal cortical terminals (Levey et Correspondence: Shao-Pii Onn, PhD, Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, Onn@bns.pitt.edu. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2011 March 8. Sesack et al., 1994;Delle Donne et al., 1997;Filoux et al., 1988;Jansson et al., 1998) plays an important role in regulating cortico-striatal/accumbal glutamate transmission in spiny projection neurons (Brown and Arbuthnott, 1983;O'Donnell and Grace, 1994;Flores-Hernandez et al., 1997;Cepeda et al., 2001; Bamford et al., 2004). One molecule involved in dopamine (DA) transmission, DA and cyclic-AMP Regulated Phosphoprotein-32 (DARPP-32), exerts complex actions on DA-dependent modulation in limbic prefrontal corticoaccumbens circuits and i...

Sucrose Abstinence and Environmental Enrichment Effects on Mesocorticolimbic DARPP32 in Rats

“…D1 receptors affect GABA neurotransmission 33 and D1 agonism increases NMDA receptor trafficking 34 . DARPP32 itself mediates NMDA trafficking, and facilitates non-synaptic communication between neurons 35 . Connecting DARPP32 back to EE, it was recently reported that 24 h EE resulted in changes in spine morphology in the nucleus accumbens.…”

A novel mechanism for switching a neural system from one state to another

“…In the retina, the regulator is a neuromodulator, dopamine: Light triggers the release of dopamine, which closes gap junctions via second messengers (McMahon et al, 1989 ; Dong and McReynolds, 1991 ; Weiler et al, 2000 ). Dopamine, as well as noradrenaline and histamine, have been found to open and close gap junctions in several of these brain areas (Cepeda et al, 1989 ; Yang and Hatton, 2002 ; Onn et al, 2008 ; Zsiros and Maccaferri, 2008 ).…”