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. Published by Elsevier Ltd on behalf of IBRO.
Dopamine and cyclic-AMP regulated phosphoprotein-32-dependent modulation of prefrontal cortical input and intercellular coupling in mouse accumbens spiny and aspiny neurons
Creators
S. -P. Onn - Drexel University
M. Lin - Drexel University
J. -J. Liu - Drexel University
A. A. Grace - University of Pittsburgh
Publication Details
Neuroscience, v 151(3), pp 802-816
Publisher
Elsevier
Number of pages
15
Grant note
R01MH057440 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
MH 57440; MH45156; R01 MH063498; R01 MH057440; MH 63498; R37 MH057440-13; R37 MH057440; P50 MH045156 / NIMH NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
Resource Type
Journal article
Language
English
Academic Unit
Neurobiology and Anatomy; Center for Weight, Eating and Lifestyle Science (WELL) [Historical]
Web of Science ID
WOS:000253188000018
Scopus ID
2-s2.0-38749110763
Other Identifier
991019168628804721
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