Localization of DARPP-32 and inhibitor-1 in area 9 of Macaca mulatta prefrontal cortex

• Type of Material: Article
• Authors: Jill R. Glausier, Emory University; Marcelia Maddox, Emory University; Hugh C. Hemmings, The Rockefeller University; Angus C. Nairn, The Rockefeller University; Paul Greengard, The Rockefeller University; E Christopher Muly, Emory University
• Language: English
• Date: 2010-05-05
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://www.journals.elsevier.com/neuroscience/
• Title of Journal or Parent Work: Neuroscience
• ISSN: 0306-4522
• Volume: 167
• Issue: 2
• Start Page: 428
• End Page: 438
• Grant/Funding Information: This work was supported by MH076372 from NIMH to JRBNS56315 from NIH to HCHDA10044 from NIH to ACNMH074866 from NIMH to ACN and PG; RR00165 from NIH, a Merit Award from the Office of Research and Development, Department of Veterans Affairs, a University Research Committee grant from Emory University and MH068789 from NIMH to ECM.
• Keywords: D5; protein phosphatase-1; dendritic spines; dopamine; D1; electron microscopy
• Research Categories: Psychology, General; Biology, Neuroscience

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 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.