GABAergic inputs from direct and indirect striatal projection neurons onto cholinergic interneurons in the primate putamen

• Type of Material: Article
• Authors: Kalynda Kari Gonzales, Emory University; Jean-Francois Pare, Emory University; Thomas Wichmann, Emory University; Yoland Smith, Emory University
• Language: English
• Date: 2013-08-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Wiley Periodicals, Inc.
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/cne.23295/abstract
• Title of Journal or Parent Work: Journal of Comparative Neurology
• ISSN: 0021-9967
• Volume: 521
• Issue: 11
• Start Page: 2502
• End Page: 2522
• Grant/Funding Information: NIH base grant to the Yerkes National Primate Research Center (RR00165).; National Institute of Health R01NS037948 (YS, TW), R01NS062876 (TW,YS), P50NS071669 (TW,YS) and F31NS066754 (KKG).
• Keywords: striatum; substance P; medium spiny neurons; GABA; enkephalin
• Research Categories: Health Sciences, Mental Health; Health Sciences, Human Development; Biology, Neuroscience

Abstract

Striatal cholinergic interneurons (ChIs) are involved in reward-dependent learning and the regulation of attention. The activity of these neurons is modulated by intrinsic and extrinsic γ-aminobutyric acid (GABA)ergic and glutamatergic afferents, but the source and relative prevalence of these diverse regulatory inputs remain to be characterized. To address this issue, we performed a quantitative ultrastructural analysis of the GABAergic and glutamatergic innervation of ChIs in the postcommissural putamen of rhesus monkeys. Postembedding immunogold localization of GABA combined with peroxidase immunostaining for choline acetyltransferase showed that 60% of all synaptic inputs to ChIs originate from GABAergic terminals, whereas 21% are from putatively glutamatergic terminals that establish asymmetric synapses, and 19% from other (non-GABAergic) sources of symmetric synapses. Double pre-embedding immunoelectron microscopy using substance P and Met-/Leu-enkephalin antibodies to label GABAergic terminals from collaterals of “direct” and “indirect” striatal projection neurons, respectively, revealed that 47% of the indirect pathway terminals and 36% of the direct pathway terminals target ChIs. Together, substance P- and enkephalin-positive terminals represent 24% of all synapses onto ChIs in the monkey putamen. These findings show that ChIs receive prominent GABAergic inputs from multiple origins, including a significant contingent from axon collaterals of direct and indirect pathway projection neurons.