Continuous cholinergic-dopaminergic updating in the nucleus accumbens underlies approaches to reward-predicting cues

Miguel Skirzewski (), Oren Princz-Lebel, Liliana German-Castelan, Alycia M. Crooks, Gerard Kyungwook Kim, Sophie Henke Tarnow, Amy Reichelt, Sara Memar, Daniel Palmer, Yulong Li, R. Jane Rylett, Lisa M. Saksida, Vania F. Prado, Marco A. M. Prado () and Timothy J. Bussey ()
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Miguel Skirzewski: Western University
Oren Princz-Lebel: Western University
Liliana German-Castelan: Western University
Alycia M. Crooks: Western University
Gerard Kyungwook Kim: Western University
Sophie Henke Tarnow: Western University
Amy Reichelt: Western University
Sara Memar: Western University
Daniel Palmer: Western University
Yulong Li: Peking University School of Life Sciences
R. Jane Rylett: Western University
Lisa M. Saksida: Western University
Vania F. Prado: Western University
Marco A. M. Prado: Western University
Timothy J. Bussey: Western University

Nature Communications, 2022, vol. 13, issue 1, 1-21

Abstract: Abstract The ability to learn Pavlovian associations from environmental cues predicting positive outcomes is critical for survival, motivating adaptive behaviours. This cued-motivated behaviour depends on the nucleus accumbens (NAc). NAc output activity mediated by spiny projecting neurons (SPNs) is regulated by dopamine, but also by cholinergic interneurons (CINs), which can release acetylcholine and glutamate via the activity of the vesicular acetylcholine transporter (VAChT) or the vesicular glutamate transporter (VGLUT3), respectively. Here we investigated behavioural and neurochemical changes in mice performing a touchscreen Pavlovian approach task by recording dopamine, acetylcholine, and calcium dynamics from D1- and D2-SPNs using fibre photometry in control, VAChT or VGLUT3 mutant mice to understand how these signals cooperate in the service of approach behaviours toward reward-predicting cues. We reveal that NAc acetylcholine-dopaminergic signalling is continuously updated to regulate striatal output underlying the acquisition of Pavlovian approach learning toward reward-predicting cues.

Date: 2022
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DOI: 10.1038/s41467-022-35601-x

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