Functional dissociation of behavioral effects from acetylcholine and glutamate released from cholinergic striatal interneurons.

Autor:	Kljakic O; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.; Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada., Janíčková H; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada., Skirzewski M; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.; Brain and Mind Institute, The University of Western Ontario, London, Ontario, Canada., Reichelt A; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.; Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada., Memar S; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.; Brain and Mind Institute, The University of Western Ontario, London, Ontario, Canada., El Mestikawy S; Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.; INSERM, CNRS, Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), Sorbonne Université, Paris, France., Li Y; State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China., Saksida LM; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.; Brain and Mind Institute, The University of Western Ontario, London, Ontario, Canada.; Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada., Bussey TJ; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.; Brain and Mind Institute, The University of Western Ontario, London, Ontario, Canada.; Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada., Prado VF; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.; Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.; Brain and Mind Institute, The University of Western Ontario, London, Ontario, Canada.; Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada., Prado MAM; Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.; Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.; Brain and Mind Institute, The University of Western Ontario, London, Ontario, Canada.; Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.
Jazyk:	angličtina
Zdroj:	FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2022 Feb; Vol. 36 (2), pp. e22135.
DOI:	10.1096/fj.202101425R
Abstrakt:	In the striatum, cholinergic interneurons (CINs) have the ability to release both acetylcholine and glutamate, due to the expression of the vesicular acetylcholine transporter (VAChT) and the vesicular glutamate transporter 3 (VGLUT3). However, the relationship these neurotransmitters have in the regulation of behavior is not fully understood. Here we used reward-based touchscreen tests in mice to assess the individual and combined contributions of acetylcholine/glutamate co-transmission in behavior. We found that reduced levels of the VAChT from CINs negatively impacted dopamine signalling in response to reward, and disrupted complex responses in a sequential chain of events. In contrast, diminished VGLUT3 levels had somewhat opposite effects. When mutant mice were treated with haloperidol in a cue-based task, the drug did not affect the performance of VAChT mutant mice, whereas VGLUT3 mutant mice were highly sensitive to haloperidol. In mice where both vesicular transporters were deleted from CINs, we observed altered reward-evoked dopaminergic signalling and behavioral deficits that resemble, but were worse, than those in mice with specific loss of VAChT alone. These results demonstrate that the ability to secrete two different neurotransmitters allows CINs to exert complex modulation of a wide range of behaviors. (© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
Databáze:	MEDLINE
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