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Author Notes:

Correspondence: Yoland Smith, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329. Email: ysmit01@emory.edu.

Authors' Contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Critical revision of the manuscript for important intellectual content: K.K. Gonzales, Y. Smith, and T. Wichmann.

Statistical analysis: K.K. Gonzales.

Obtained funding: K.K. Gonzales, Y. Smith, and T. Wichmann.

Administrative, technical, and material support: J.-F. Pare.

Study supervision: K.K. Gonzales, J.-F. Pare, Y. Smith, and T. Wichmann.

See publication for full list of author contributions.

Acknowledgments: The authors thank Susan Jenkins for her excellent assistance with immunohistochemical matters and electron microscopy and Dr. Adriana Galvan for critical reading of the manuscript.

We also thank Alex Derienko from Emory Graphic Design Service for his elegant illustration used in Figure 8 of this paper.

Disclosures: None of the authors of this paper have a conflict of interest with other people or organizations.


Research Funding:

National Institute of Health R01NS037948 (YS, TW), R01NS062876 (TW,YS), P50NS071669 (TW,YS) and F31NS066754 (KKG).

NIH base grant to the Yerkes National Primate Research Center (RR00165).


  • medium spiny neurons
  • substance P
  • enkephalin
  • GABA
  • striatum

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


Journal Title:

Journal of Comparative Neurology


Volume 521, Number 11


, Pages 2502-2522

Type of Work:

Article | Post-print: After Peer Review


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.

Copyright information:

Copyright © 2013 Wiley Periodicals, Inc.

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