Fast modulation of visual perception by basal forebrain cholinergic neurons
Open accessAbstract
The basal forebrain provides the primary source of cholinergic input to the cortex, and it has a crucial function in promoting wakefulness and arousal. However, whether rapid changes in basal forebrain neuron spiking in awake animals can dynamically influence sensory perception is unclear. Here we show that basal forebrain cholinergic neurons rapidly regulate cortical activity and visual perception in awake, behaving mice. Optogenetic activation of the cholinergic neurons or their V1 axon terminals improved performance of a visual discrimination task on a trial-by-trial basis. In V1, basal forebrain activation enhanced visual responses and desynchronized neuronal spiking; these changes could partly account for the behavioral improvement. Conversely, optogenetic basal forebrain inactivation decreased behavioral performance, synchronized cortical activity and impaired visual responses, indicating the importance of cholinergic activity in normal visual processing. These results underscore the causal role of basal forebrain cholinergic neurons in fast, bidirectional modulation of cortical processing and sensory perception.
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Stimulation of the basal forebrain can have many of the same effects as those associated with arousal and locomotion, including increased amplitude and precision of sensory evoked responses.
“Stimulation of the basal forebrain can have many of the same effects as those associated with arousal and locomotion, including increased amplitude and precision of sensory evoked responses (Goard and Dan, 2009; Pinto et al., 2013).”
From Waking state: rapid variations modulate neural and behavioral responses (2015) · cites this paper as Pinto et al., 2013
There is some evidence for the role of basal forebrain cholinergic cells in alertness.
“with some evidence for the role of basal forebrain cholinergic cells (Harris and Thiele, 2011; Lee and Dan, 2012; Pinto et al., 2013; Hangya et al., 2015; Reimer et al., 2016).”
From Ancestral Circuits for the Coordinated Modulation of Brain State (2017) · cites this paper as Pinto et al., 2013
Optogenetic stimulation of endogenous ACh release in mouse V1 desynchronizes spiking and enhances visual perceptual performance without altering overall firing rates.
“In contrast to the effects of pharmacological agents, optogenetic stimulation of endogenous ACh release in mouse V1 desynchronizes spiking and enhances visual perceptual performance, without altering overall firing rates175.”
From Mechanisms underlying gain modulation in the cortex (2020) · cites this paper as [175]
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“, with a 120-ms latency [15]), but one must also consider how fast the basal forebrain reacts to visual input.”
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- Authors
- Pinto, L., Goard, M. J., Estandian, D., Xu, M., Kwan, A. C., Lee, S.-H., Harrison, T. C., Feng, G., & Dan, Y.
- Affiliations
- Howard Hughes Medical Institute (US)
- McGovern Institute for Brain Research (US)
- Corresponding author
- Dan, Yang
- Venue
- Nature Neuroscience
- Published
- 2013-10-27
- Volume
- 16
- Issue
- 12
- Pages
- 1857-1863
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4201942
- OpenAlex
- W1971638449
- Cited by
- 529
- References
- 56
- Citations by year
- 2026: 20 · 2025: 27 · 2024: 44 · 2023: 42 · 2022: 45 · 2021: 44 · 2020: 48 · 2019: 48 · 2018: 50 · 2017: 44 · 2016: 42 · 2015: 43 · 2014: 32
- FWCI
- 21.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- eScholarship (California Digital Library) (submittedVersion)
- KAIST Institutional Repository (KAIST) (submittedVersion)
- PMC
- Funders
- National Institute of Mental Health (RC1MH088434)
- National Eye Institute (R01EY018861)
- National Institute of Neurological Disorders and Stroke (F31NS059258, F31NS084696)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Visual perception and processing mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- basal forebrain cholinergic neurons, visual perception, visual cortex, primary visual cortex, cortical desynchronization, neuronal spiking, visual discrimination, optogenetic stimulation, cholinergic modulation, sensory processing
- MeSH terms
- Channelrhodopsins, Acetylcholine, Action Potentials, Animals, Cholera Toxin, Choline O-Acetyltransferase, Exercise Test, Glutamate Decarboxylase, Luminescent Proteins, Mice, Inbred C57BL, Mice, Transgenic, Neural Pathways, Photic Stimulation, Visual Perception, Prosencephalon, Proton Pumps, Archaeal Proteins, RNA, Untranslated, Halorhodopsins, Mice, Cholinergic Neurons
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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