Complementary roles of serotonergic and cholinergic systems in decisions about when to act
Open accessAbstract
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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Self-citation
- 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)
- PMC
- PMC8926843
- 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
- hybrid
- doi.org
- Licence
- 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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