Cited by 29Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesNeuroscience and Neuropharmacology Research

Complementary roles of serotonergic and cholinergic systems in decisions about when to act

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Khalighinejad, Nima, Manohar, Sanjay, Husain, Masud, Rushworth, Matthew F.S.·2022·Current Biology

Abstract

Decision-making not only involves deciding about which action to choose but when and whether to initiate an action in the first place. Macaque monkeys tracked number of dots on a screen and could choose when to make a response. The longer the animals waited before responding, the more dots appeared on the screen and the higher the probability of reward. Monkeys waited longer before making a response when a trial's value was less than the environment's average value. Recordings of brain activity with fMRI revealed that activity in dorsal raphe nucleus (DRN)-a key source of serotonin (5-HT)-tracked average value of the environment. By contrast, activity in the basal forebrain (BF)-an important source of acetylcholine (ACh)-was related to decision time to act as a function of immediate and recent past context. Interactions between DRN and BF and the anterior cingulate cortex (ACC), another region with action initiation-related activity, occurred as a function of the decision time to act. Next, we performed two psychopharmacological studies. Manipulating systemic 5-HT by citalopram prolonged the time macaques waited to respond for a given opportunity. This effect was more evident during blocks with long inter-trial intervals (ITIs) where good opportunities were sparse. Manipulating systemic acetylcholine (ACh) by rivastigmine reduced the time macaques waited to respond given the immediate and recent past context, a pattern opposite to the effect observed with 5-HT. These findings suggest complementary roles for serotonin/DRN and acetylcholine/BF in decisions about when to initiate an action.

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  1. [43]Fox J. Weisberg S. An R Companion to Applied Regression Third Edition 2018 SAGE Publications

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Authors
Khalighinejad, N., Manohar, S., Husain, M., & Rushworth, M. F. S.
Affiliations
University of Oxford (GB)
Corresponding author
Khalighinejad, Nima
Venue
Current Biology
Publisher
Elsevier BV
Published
2022-03
Volume
32
Issue
5
Pages
1150-1162.e7
ISSN
0960-9822 (ISSN-L)
OpenAlex
W4211147407
Cited by
29
References
44
Citations by year
2026: 8 · 2025: 5 · 2024: 10 · 2023: 5 · 2022: 1
FWCI
2.32
Type
journal article
Language
en
Open access
Locations
  • Current Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Wellcome Trust
  • Medical Research Council (MR/P024955/1)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
decision-making, serotonin, acetylcholine, dorsal raphe nucleus, basal forebrain, anterior cingulate cortex, citalopram, rivastigmine, intertrial interval, waiting behavior, macaque, psychopharmacology
MeSH terms
Acetylcholine, Animals, Reward, Serotonin, Cholinergic Agents, Dorsal Raphe Nucleus

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