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Localization of dopamine- and cAMP-regulated phosphoprotein-32 and inhibitor-1 in area 9 of Macaca mulatta prefrontal cortex.

TitleLocalization of dopamine- and cAMP-regulated phosphoprotein-32 and inhibitor-1 in area 9 of Macaca mulatta prefrontal cortex.
Publication TypeJournal Article
Year of Publication2010
AuthorsGlausier JR, Maddox M, Hemmings HC, Nairn AC, Greengard P, Muly EC
JournalNeuroscience
Volume167
Issue2
Pagination428-38
Date Published2010 May 5
ISSN1873-7544
KeywordsAnimals, Dendritic Spines, Dopamine and cAMP-Regulated Phosphoprotein 32, Macaca mulatta, Microscopy, Immunoelectron, Neuropil, Prefrontal Cortex, Presynaptic Terminals, Protein Phosphatase 1, Proteins, Receptors, Dopamine D1
Abstract

The actions of dopamine D1 family receptors (D1R) depend upon a signal transduction cascade that modulates the phosphorylation state of important effector proteins, such as glutamate receptors and ion channels. This is accomplished both through activation of protein kinase A (PKA) and the inhibition of protein phosphatase-1 (PP1). Inhibition of PP1 occurs through PKA-mediated phosphorylation of dopamine- and cAMP-regulated phosphoprotein 32 kDa (DARPP-32) or the related protein inhibitor-1 (I-1), and the availability of DARPP-32 is essential to the functional outcome of D1R activation in the basal ganglia. While D1R activation is critical for prefrontal cortex (PFC) function, especially working memory, the functional role played by DARPP-32 or I-1 is less clear. In order to examine this more thoroughly, we have utilized immunoelectron microscopy to quantitatively determine the localization of DARPP-32 and I-1 in the neuropil of the rhesus monkey PFC. Both were distributed widely in the different components of the neuropil, but were enriched in dendritic shafts. I-1 label was more frequently identified in axon terminals than was DARPP-32, and DARPP-32 label was more frequently identified in glia than was I-1. We also quantified the extent to which these proteins were found in dendritic spines. DARPP-32 and I-1 were present in small subpopulations of dendritic spines, (4.4% and 7.7% and respectively), which were substantially smaller than observed for D1R in our previous studies (20%). Double-label experiments did not find evidence for colocalization of D1R and DARPP-32 or I-1 in spines or terminals. Thus, at the least, not all prefrontal spines which contain D1R also contain I-1 or DARPP-32, suggesting important differences in D1R signaling in the PFC compared to the striatum.

DOI10.1016/j.neuroscience.2010.02.014
Alternate JournalNeuroscience
PubMed ID20156529
PubMed Central IDPMC2863358
Grant ListDA10044 / DA / NIDA NIH HHS / United States
F31 MH076372 / MH / NIMH NIH HHS / United States
F31 MH076372-03 / MH / NIMH NIH HHS / United States
MH068789 / MH / NIMH NIH HHS / United States
MH074866 / MH / NIMH NIH HHS / United States
MH076372 / MH / NIMH NIH HHS / United States
NS56315 / NS / NINDS NIH HHS / United States
P01 DA010044 / DA / NIDA NIH HHS / United States
P01 DA010044-020003 / DA / NIDA NIH HHS / United States
P50 MH068789 / MH / NIMH NIH HHS / United States
P50 MH068789-010006 / MH / NIMH NIH HHS / United States
P50 MH074866 / MH / NIMH NIH HHS / United States
P50 MH074866-020001 / MH / NIMH NIH HHS / United States
P50 MH074866-020003 / MH / NIMH NIH HHS / United States
P51 RR000165-498412 / RR / NCRR NIH HHS / United States
R01 NS056315 / NS / NINDS NIH HHS / United States
R01 NS056315-01A2 / NS / NINDS NIH HHS / United States
R01 NS056315-04 / NS / NINDS NIH HHS / United States
RR00165 / RR / NCRR NIH HHS / United States