An acetylcholine-activated microcircuit drives temporal dynamics of cortical activity

Chen, Naiyan; Sugihara, Hiroki; Sur, Mriganka

doi:10.1038/nn.4002

Cited by 210Neural dynamics and brain functionNeuroscience and Neuropharmacology ResearchVisual perception and processing mechanisms

An acetylcholine-activated microcircuit drives temporal dynamics of cortical activity

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Chen, Naiyan, Sugihara, Hiroki, Sur, Mriganka·2015·Nature Neuroscience

DOI 10.1038/nn.4002PMC PMC4446146

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Abstract

Cholinergic modulation of cortex powerfully influences information processing and brain states, causing robust desynchronization of local field potentials and strong decorrelation of responses between neurons. We found that intracortical cholinergic inputs to mouse visual cortex specifically and differentially drive a defined cortical microcircuit: they facilitate somatostatin-expressing (SOM) inhibitory neurons that in turn inhibit parvalbumin-expressing inhibitory neurons and pyramidal neurons. Selective optogenetic inhibition of SOM responses blocked desynchronization and decorrelation, demonstrating that direct cholinergic activation of SOM neurons is necessary for this phenomenon. Optogenetic inhibition of vasoactive intestinal peptide-expressing neurons did not block desynchronization, despite these neurons being activated at high levels of cholinergic drive. Direct optogenetic SOM activation, independent of cholinergic modulation, was sufficient to induce desynchronization. Together, these findings demonstrate a mechanistic basis for temporal structure in cortical populations and the crucial role of neuromodulatory drive in specific inhibitory-excitatory circuits in actively shaping the dynamics of neuronal activity.

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Neuromodulatory inputs, such as acetylcholine, alter the correlation statistics of synaptic activity in the cortex.
“Neuromodulatory inputs, such as acetylcholine (ACh), also alter the correlation statistics of synaptic activity in the cortex73,75.”
From Mechanisms underlying gain modulation in the cortex (2020) · cites this paper as [75]
Cholinergic input to cortex increases SST+ interneuron activity, thus increasing inhibition of PV+ cells and pyramidal neurons and desynchronizing cortical networks and synaptic inputs to individual neurons.
“Cholinergic input to the cortex increases SST+ interneuron activity, thus increasing inhibition of PV+ cells and pyramidal neurons and desynchronizing cortical networks75 and synaptic inputs to individual neurons.”
From Mechanisms underlying gain modulation in the cortex (2020) · cites this paper as [75]

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Authors: Chen, N., Sugihara, H., & Sur, M.
Affiliations: Massachusetts Institute of Technology (US)
Corresponding author: Sur, Mriganka
ORCID: Chen, Naiyan
Sur, Mriganka
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2015-04-27
Volume: 18
Issue: 6
Pages: 892-902
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn.4002
PMC: PMC4446146
OpenAlex: W1980563724
Cited by: 210
References: 67
Citations by year: 2026: 14 · 2025: 16 · 2024: 23 · 2023: 15 · 2022: 21 · 2021: 15 · 2020: 17 · 2019: 22 · 2018: 21 · 2017: 23 · 2016: 20 · 2015: 3
FWCI: 13.42
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
PMC
Funders: National Eye Institute (R01EY018648, R01EY007023)
National Institute of Neurological Disorders and Stroke (U01NS090473)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Visual perception and processing mechanisms
Keywords: acetylcholine, cholinergic modulation, somatostatin interneurons, parvalbumin interneurons, cortical microcircuits, neuromodulation, vasoactive intestinal peptide neurons, optogenetic inhibition, mouse visual cortex
MeSH terms: Acetylcholine, Animals, Cerebral Cortex, Cortical Synchronization, Interneurons, Mice, Inbred C57BL, Nerve Net, Neurons, Parasympathetic Nervous System, Parvalbumins, Photic Stimulation, Somatostatin, Vasoactive Intestinal Peptide, Visual Pathways, Pyramidal Cells, Excitatory Postsynaptic Potentials, Mice, Optogenetics

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An acetylcholine-activated microcircuit drives temporal dynamics of cortical activity

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