Differential regulation of fronto-executive function by the monoamines and acetylcholine
Abstract
The prefrontal cortex (PFC) is innervated by the monoamines, dopamine (DA), noradrenaline (NA), and serotonin, as well as acetylcholine, and the marked influence of these neurochemical systems on prefrontal working memory processes has been widely described. However, their potentially, differential contribution to prefrontal functioning is less well understood. This paper reviews evidence to support the hypothesis that these neurochemical systems recruit distinct fronto-executive operations. Direct comparison of the effects of manipulations of these neuromodulators within PFC on performance of an attentional set-shifting paradigm reveals their differential contribution to distinct task stages. Depletion of prefrontal serotonin selectively disrupts reversal learning but not attentional set formation or set shifting. In contrast, depletion of prefrontal DA disrupts set formation but not reversal learning. NA depletion on the other hand specifically impairs set-shifting, whereas its effects on reversal learning remain unclear. Finally, depletion of prefrontal acetylcholine has no effect on either set formation or set shifting but impairs serial reversal learning. Because these neurochemical systems are known to represent distinct states of stress, arousal, attention, and affect, it is postulated that they augment the different types of executive operation that are recruited and performed within these states via a synergistic interaction with the PFC.
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Both norepinephrine and dopamine have an inverted-U dose effect on PFC function, whereby either too little or too much impairs PFC function, while moderate levels strengthen and sculpt inputs to optimize PFC function.
“It is now known that both NE and DA have an inverted-U dose effect on PFC function, whereby either too little (e.g., depletion or fatigue) or too much (e.g., uncontrollable stress) impairs PFC function, while moderate levels of catecholamine released when a subject is alert and interested strengthen and sculpt inputs to optimize PFC function based on environmental demands.”
From Catecholamine Influences on Dorsolateral Prefrontal Cortical Networks (2011) · cites this paper as [7]
The dorsolateral PFC is especially sensitive to levels of norepinephrine and dopamine, whereby either too little or too much markedly impairs PFC function.
“The dorsolateral PFC is especially sensitive to levels of norepinephrine and dopamine, whereby either too little or too much markedly impairs PFC function.”
From Catecholamine Influences on Dorsolateral Prefrontal Cortical Networks (2011) · cites this paper as [7]
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Self-citation
- Authors
- Robbins, T., & Roberts, A.
- Affiliations
- University of Cambridge (GB)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-08-27
- Volume
- 17
- Issue
- suppl 1
- Pages
- i151-i160
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2168100629
- Cited by
- 279
- References
- 19
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 13 · 2020: 7 · 2019: 6 · 2018: 11 · 2017: 20 · 2016: 18 · 2015: 26 · 2014: 22 · 2013: 25 · 2012: 30
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- prefrontal cortex, monoamines, acetylcholine, dopamine, norepinephrine, serotonin, set-shifting, reversal learning, serial reversal learning, neuromodulation, working memory
- MeSH terms
- Acetylcholine, Animals, Attention, Biogenic Amines, Cognition, Dopamine, Frontal Lobe, Memory, Short-Term, Psychomotor Performance, Serotonin, Neurotransmitter Agents
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