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Cortical interneurons that specialize in disinhibitory control
Open accessAbstract
In the mammalian cerebral cortex the diversity of interneuronal subtypes underlies a division of labour subserving distinct modes of inhibitory control. A unique mode of inhibitory control may be provided by inhibitory neurons that specifically suppress the firing of other inhibitory neurons. Such disinhibition could lead to the selective amplification of local processing and serve the important computational functions of gating and gain modulation. Although several interneuron populations are known to target other interneurons to varying degrees, little is known about interneurons specializing in disinhibition and their in vivo function. Here we show that a class of interneurons that express vasoactive intestinal polypeptide (VIP) mediates disinhibitory control in multiple areas of neocortex and is recruited by reinforcement signals. By combining optogenetic activation with single-cell recordings, we examined the functional role of VIP interneurons in awake mice, and investigated the underlying circuit mechanisms in vitro in auditory and medial prefrontal cortices. We identified a basic disinhibitory circuit module in which activation of VIP interneurons transiently suppresses primarily somatostatin- and a fraction of parvalbumin-expressing inhibitory interneurons that specialize in the control of the input and output of principal cells, respectively. During the performance of an auditory discrimination task, reinforcement signals (reward and punishment) strongly and uniformly activated VIP neurons in auditory cortex, and in turn VIP recruitment increased the gain of a functional subpopulation of principal neurons. These results reveal a specific cell type and microcircuit underlying disinhibitory control in cortex and demonstrate that it is activated under specific behavioural conditions.
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In the citing paper
“The targeting of SST interneurons by VIP cells appears to be a generalized motif across brain structures including somatosensory, visual, and auditory cortices, and this specific disinhibitory microcircuit is important in sensory processing that, in some circumstances, demonstrates behavioral state dependence (363, 553, 660, 905, 906, 908, 1246, 1270).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [908]
Experimental — accuracy not yet measuredIn the citing paper
“PFC in awake mice also has a basic disinhibitory circuit module in which activation of VIP+ interneurons transiently suppresses primarily SST+ and a fraction of PV+ interneurons 30.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [30]
In the citing paper
“These elements can be task-dependently recruited into larger brain networks for systems-level information processing and computation, representing their distal behavioural and cognitive functions59,60.”
From The diversity of GABAergic neurons and neural communication elements (2019) · cites this paper as [60]
In the citing paper
“More recently, a number of functional studies in both hippocampus and neocortex have taken advantage of transgenic animals and modern circuit mapping tools to functionally confirm that subsets of CR- and VIP-expressing interneurons do indeed mediate circuit disinhibition by selectively targeting other interneurons over pyramidal cells (185, 363, 652, 906, 908, 1145, 1270).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [908]
In the citing paper
“Indeed, these driver lines have been successfully used in a number of recent studies to dissect circuit functions of ISIs in both hippocampus and neocortex (363, 553, 652, 906, 908, 1145, 1270).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [908]
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Metadata
- Authors
- Pi, H.-J., Hangya, B., Kvitsiani, D., Sanders, J. I., Huang, Z. J., & Kepecs, A.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Venue
- Nature
- Published
- 2013-10-06
- Volume
- 503
- Issue
- 7477
- Pages
- 521-524
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4017628
- OpenAlex
- W1992910467
- Cited by
- 1,136
- References
- 37
- Citations by year
- 2026: 72 · 2025: 98 · 2024: 76 · 2023: 77 · 2022: 91 · 2021: 111 · 2020: 91 · 2019: 102 · 2018: 98 · 2017: 97 · 2016: 83 · 2015: 79 · 2014: 55 · 2013: 5
- FWCI
- 36.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of Mental Health (U01MH078844)
- National Institute of Neurological Disorders and Stroke (R01NS075531)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- disinhibition, vasoactive intestinal peptide, cortical interneurons, inhibitory interneurons, somatostatin interneurons, parvalbumin interneurons, reinforcement learning, reward and punishment, auditory cortex, medial prefrontal cortex, gain modulation, optogenetic stimulation, single-unit recording, neocortex, principal neurons
- MeSH terms
- Acoustic Stimulation, Animals, Auditory Cortex, Cerebral Cortex, Discrimination, Psychological, Female, Interneurons, Male, Mice, Inbred C57BL, Neural Inhibition, Parvalbumins, Punishment, Reward, Somatostatin, Vasoactive Intestinal Peptide, Wakefulness, Prefrontal Cortex, Mice, Single-Cell Analysis, Optogenetics
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