Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention

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Abstract

Neocortical choline acetyltransferase (ChAT)-expressing interneurons are a subclass of vasoactive intestinal peptide (ChAT-VIP) neurons of which circuit and behavioural function are unknown. Here, we show that ChAT-VIP neurons directly excite neighbouring neurons in several layers through fast synaptic transmission of acetylcholine (ACh) in rodent medial prefrontal cortex (mPFC). Both interneurons in layers (L)1–3 as well as pyramidal neurons in L2/3 and L6 receive direct inputs from ChAT-VIP neurons mediated by fast cholinergic transmission. A fraction (10–20%) of postsynaptic neurons that received cholinergic input from ChAT-VIP interneurons also received GABAergic input from these neurons. In contrast to regular VIP interneurons, ChAT-VIP neurons did not disinhibit pyramidal neurons. Finally, we show that activity of these neurons is relevant for behaviour and they control attention behaviour distinctly from basal forebrain ACh inputs. Thus, ChAT-VIP neurons are a local source of cortical ACh that directly excite neurons throughout cortical layers and contribute to attention.

Abstract

VIP interneurons have been shown to disinhibit pyramidal neurons by inhibiting other interneuron types. Here, the authors report that ChAT-VIP subtype of interneurons directly excite pyramidal neurons in multiple layers via fast cholinergic neurotransmission.

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Most cited references 51

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Cortical interneurons that specialize in disinhibitory control

Hyun Jae Pi, Balázs Hangya, Duda Kvitsiani … (2013)

In the mammalian cerebral cortex, the diversity of interneuronal subtypes underlies a division of labor subserving distinct modes of inhibitory control 1–7 . 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 8,9 . Although several interneuron populations are known to target other interneurons to varying degrees 10–15 , 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 3,6,16,17 . 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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A disinhibitory circuit mediates motor integration in the somatosensory cortex.

Soohyun Lee, Illya Kruglikov, Z. Josh Huang … (2013)

The influence of motor activity on sensory processing is crucial for perception and motor execution. However, the underlying circuits are not known. To unravel the circuit by which activity in the primary vibrissal motor cortex (vM1) modulates sensory processing in the primary somatosensory barrel cortex (S1), we used optogenetics to examine the long-range inputs from vM1 to the various neuronal elements in S1. We found that S1-projecting vM1 pyramidal neurons strongly recruited vasointestinal peptide (VIP)-expressing GABAergic interneurons, a subset of serotonin receptor-expressing interneurons. These VIP interneurons preferentially inhibited somatostatin-expressing interneurons, neurons that target the distal dendrites of pyramidal cells. Consistent with this vM1-mediated disinhibitory circuit, the activity of VIP interneurons in vivo increased and that of somatostatin interneurons decreased during whisking. These changes in firing rates during whisking depended on vM1 activity. Our results suggest previously unknown circuitry by which inputs from motor cortex influence sensory processing in sensory cortex.

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The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry.

T. W. Robbins (2002)

The developmental history and application of the 5-choice serial reaction time task (5CSRTT) for measuring effects of drugs and other manipulations on attentional performance (and stimulus control) in rats is reviewed. The 5CSRTT has been used for measuring effects of systemic drug treatments and also central manipulations such as neurochemical lesions on various aspects of attentional control, including sustained, selective and divided attention--and is relevant to the definition of neural systems of attention and applications to human disorders such as attention deficit/hyperactivity disorder (ADHD) and Alzheimer's disease. The 5CSRTT is implemented in a specially designed operant chamber with multiple response locations ('nine-hole box') using food reinforcers to maintain performance on baseline sessions (about 100 trials) at criterion levels of accuracy and trials completed. The 5CSRTT can be used for measuring various aspects of attentional control over performance with its main measures of accuracy, premature responding, correct response latencies and latency to collect earned food pellets. The data reviewed include studies mainly of systemic and intra-cerebral effects of adrenoceptor, dopamine receptor, serotoninergic receptor and cholinergic receptor agents. These are compared with investigations of effects of selective chemical neurotoxins and excitotoxins applied to discrete parts of the forebrain, in order to define the neural and neurochemical substrates of attentional function. Furthermore, these results are integrated with findings from in vivo microdialysis in freely moving rats or metabolic studies. The monoaminergic and cholinergic systems appear to play separable roles in different aspects of performance controlled by the 5CSRTT, in neural systems centred on the prefrontal cortex, cingulate cortex and striatum. These conclusions are considered in the methodological and theoretical context of other psychopharmacological studies of attention in animals and humans.

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Author and article information

Contributors

Tommy Pattij:

ORCID: http://orcid.org/0000-0002-0079-7385

t.pattij@vumc.nl

Huibert D. Mansvelder:

ORCID: http://orcid.org/0000-0003-1365-5340

h.d.mansvelder@vu.nl

Journal

Journal ID (nlm-ta): Nat Commun

Journal ID (iso-abbrev): Nat Commun

Title: Nature Communications

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2041-1723

Publication date (Electronic): 21 November 2019

Publication date PMC-release: 21 November 2019

Publication date Collection: 2019

Volume: 10

Electronic Location Identifier: 5280

Affiliations

[1 ]ISNI 0000 0004 1754 9227, GRID grid.12380.38, Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), , Vrije Universiteit, ; Amsterdam Neuroscience, The Netherlands

[2 ]ISNI 0000 0004 1754 9227, GRID grid.12380.38, Department of Anatomy and Neurosciences, Amsterdam UMC, , Vrije Universiteit, ; Amsterdam Neuroscience, The Netherlands

[3 ]ISNI 0000 0004 1754 9227, GRID grid.12380.38, Present Address: Department of Anatomy and Neurosciences, Clinical Neuroscience, Amsterdam UMC, , Vrije Universiteit, ; Amsterdam Neuroscience, The Netherlands

[4 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Present Address: MRC Centre-Developmental Neurobiology, King’s College London, ; London, UK

Author information

Anna A. Galakhova http://orcid.org/0000-0002-5538-0624

Tim Kroon http://orcid.org/0000-0002-0344-8682

Roel de Haan http://orcid.org/0000-0002-0499-5565

Wilma D. J. van den Berg http://orcid.org/0000-0002-6175-5357

Natalia A. Goriounova http://orcid.org/0000-0002-5917-983X

Tommy Pattij http://orcid.org/0000-0002-0079-7385

Huibert D. Mansvelder http://orcid.org/0000-0003-1365-5340

Article

Publisher ID: 13244

DOI: 10.1038/s41467-019-13244-9

PMC ID: 6872593

PubMed ID: 31754098

SO-VID: 984614cf-55b4-4332-888a-1225d2512db1

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 16 October 2019

Date accepted : 29 October 2019

Funding

Funded by: FundRef https://doi.org/10.13039/100010663, EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council);

Award ID: 281443

Award Recipient : Huibert D. Mansvelder

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ScienceOpen disciplines: Uncategorized

Keywords: neuroscience,neural circuits,synaptic transmission

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ScienceOpen disciplines: Uncategorized

Keywords: neuroscience, neural circuits, synaptic transmission

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Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention

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Karger: Neurology and Neuroscience

Most cited references 51

Cortical interneurons that specialize in disinhibitory control

A disinhibitory circuit mediates motor integration in the somatosensory cortex.

The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry.

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Cited by 41

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