Title

Elimination of the Vesicular Acetylcholine Transporter in the Striatum Reveals Regulation of Behaviour by Cholinergic-Glutamatergic Co-Transmission

Authors

Monica S. Guzman, The University of Western Ontario
Xavier De Jaeger, The University of Western Ontario
Sanda Raulic, The University of Western Ontario
Ivana A. Souza, The University of Western Ontario
Alex X. Li, The University of Western Ontario
Susanne Schmid, The University of Western Ontario
Ravi S. Menon, The University of Western Ontario
Raul R. Gainetdinov, Italian Institute of Technology, Genova, Italy
Marc G. Caron, Duke University
Robert Bartha, The University of Western Ontario
Vania F. Prado, The University of Western Ontario
Marco A. M. Prado, The University of Western Ontario

Document Type

Article

Publication Date

11-8-2011

Journal

PLoS Biology

Volume

9

Issue

11

URL with Digital Object Identifier

http://dx.doi.org/10.1371/journal.pbio.1001194

Abstract

Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT) from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN) and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.

Notes

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