Prefrontal Acetylcholine Release Controls Cue Detection on Multiple Timescales
Open accessAbstract
Cholinergic neurons originating from the basal forebrain innervate the entire cortical mantle. Choline-sensitive microelectrodes were used to measure the synaptic release of cortical acetylcholine (ACh) at a subsecond resolution in rats performing a task involving the detection of cues. Cues that were detected, defined behaviorally, evoked transient increases in cholinergic activity (at the scale of seconds) in the medial prefrontal cortex (mPFC), but not in a nonassociational control region (motor cortex). In trials involving missed cues, cholinergic transients were not observed. Cholinergic deafferentation of the mPFC, but not motor cortex, impaired cue detection. Furthermore, decreases and increases in precue cholinergic activity predicted subsequent cue detection or misses, respectively. Finally, cue-evoked cholinergic transients were superimposed over slower (at the timescale of minutes) changes in cholinergic activity. Cortical cholinergic neurotransmission is regulated on multiple timescales to mediate the detection of behaviorally significant cues and to support cognitive performance.
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Nicotine can stimulate the firing of both POMC neurons that signal satiety and neuropeptide Y (NPY) neurons that stimulate food seeking.
“nicotine can stimulate the firing of both POMC neurons that signal satiety, and neuropeptide Y (NPY) neurons that stimulate food seeking (Parikh et al. 2007(Parikh et al. , 2008)).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Parikh et al. 2007
Mice lacking the β2, but not the α7, subunit show impaired performance in an attentional task.
“mice lacking the β2, but not the α7, subunit show impaired performance in an attentional task (Parikh et al. 2007(Parikh et al. , 2008)).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Parikh et al. 2007
Rapid acetylcholine transients in the mPFC are correlated with attention to brief cues.
“rapid acetylcholine transients in the mPFC are correlated with attention to brief cues”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Parikh et al. 2007
In a slice preparation, the effects of nicotine on firing of POMC neurons persist longer than firing of NPY neurons.
“in a slice preparation, the effects of nicotine on firing of POMC neurons persist longer than firing of NPY neurons (Parikh et al. 2007(Parikh et al. , 2008))”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Parikh et al. 2007
The timing of the peak amplitude of cholinergic transients varied with the duration of the interval between cue and reward, with peak times at about 1.5 s after cue presentation in animals trained on shortest cue-reward intervals (2±1 s).
“Furthermore, the timing of the peak amplitude varied with the duration of the interval between cue and reward, with peak times at about 1.5 s after cue presentation recorded in animals trained on shortest cue-reward intervals (2±1 s; see Parikh et al, 2007).”
From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Parikh et al, 2007
In the medial prefrontal cortex, cues that were detected evoked transient increases in cholinergic activity.
“In the mPFC, cues that were detected evoked transient increases in cholinergic activity (Figure 1).”
From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Parikh et al, 2007
The presence or absence of reward and reward-related behavior did not contribute to the generation of cholinergic transients.
“Recordings from such trials as well as from several control procedures indicated that the presence or absence of reward and reward-related behavior did not contribute to the generation of cholinergic transients.”
From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Parikh et al, 2007
This results in an excitatory feedback process that drives the large transient increase in acetylcholine seen with cue detection.
“This results in an excitatory feedback process that drives the large transient increase in acetylcholine seen with cue detection (Parikh et al, 2007), as shown in Figure 3B.”
From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Parikh et al, 2007
The transition from encoding to retrieval could be mediated by changes in cholinergic neurotransmission on a time scale of the sort demonstrated with amperometry in the neocortex.
“This transition from encoding to retrieval could be mediated by changes in cholinergic neurotransmission on a time scale of the sort demonstrated with amperometry in the neocortex (Parikh et al., 2007).”
From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Parikh et al., 2007
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Self-citation
- Authors
- Parikh, V., Kozak, R., Martinez, V., & Sarter, M.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Sarter, Martin
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 56
- Issue
- 1
- Pages
- 141-154
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2084212
- OpenAlex
- W2101491694
- Cited by
- 623
- References
- 76
- Citations by year
- 2026: 15 · 2025: 25 · 2024: 33 · 2023: 34 · 2022: 28 · 2021: 37 · 2020: 41 · 2019: 28 · 2018: 48 · 2017: 38 · 2016: 32 · 2015: 43 · 2014: 47 · 2013: 44 · 2012: 31
- FWCI
- 9.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2116 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (1 K02 MH01072, K02MH001072, R03MH073600)
- National Institute of Neurological Disorders and Stroke (R01NS037026, 5 R01 NS37026)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- acetylcholine release, medial prefrontal cortex, cholinergic neurotransmission, cue detection, cholinergic deafferentation, basal forebrain cholinergic neurons, motor cortex, multiple time scales, cognitive performance, rats
- MeSH terms
- Acetylcholine, Analysis of Variance, Animals, Appetitive Behavior, Behavior, Animal, Cues, Electrochemistry, Food Deprivation, Male, Microelectrodes, Rats, Inbred F344, Reaction Time, Reward, Time Factors, Prefrontal Cortex, Rats
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