TY - JOUR
T1 - Dopamine and cyclic-AMP regulated phosphoprotein-32-dependent modulation of prefrontal cortical input and intercellular coupling in mouse accumbens spiny and aspiny neurons
AU - Onn, S. P.
AU - Lin, M.
AU - Liu, J. J.
AU - Grace, A. A.
N1 - Funding Information:
This work was supported by USPHS MH 63498 (S.-P. Onn) and MH 57440 and MH45156 (A.A.G.). The authors would like to thank Dr. P. Greengard at Rockefeller University and Drs. G. Snyder and A. Fienberg at Intracellular Therapeutics Inc. for their helpful comments and for the generous supply of DARPP-32 knockout mice. We also thank Dr. E. Gracely, professor in statistics, at Drexel University for his assistance in statistics used in this study.
PY - 2008/2/6
Y1 - 2008/2/6
N2 - 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.
AB - 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.
KW - DA D1 and D2 receptor
KW - excitatory and inhibitory synaptic transmission
KW - mouse accumbens neurons
KW - non-synaptic gap junction-mediated morphological coupling
KW - sharp-electrode recording
KW - whole cell recording
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U2 - 10.1016/j.neuroscience.2007.11.019
DO - 10.1016/j.neuroscience.2007.11.019
M3 - Article
C2 - 18155847
AN - SCOPUS:38749110763
SN - 0306-4522
VL - 151
SP - 802
EP - 816
JO - Neuroscience
JF - Neuroscience
IS - 3
ER -