Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention
Open accessPreprint — published as 10.1038/s41467-019-13244-9 · Paper page
Abstract
Summary Neocortical choline acetyltransferase (ChAT)-expressing interneurons are a subclass of vasoactive intestinal peptide (ChAT-VIP) neurons of which circuit and behavioural function are unknown. It has also not been addressed whether these neurons release both neurotransmitters acetylcholine (ACh) and GABA. Here, we find that in the medial prefrontal cortex (mPFC), ChAT-VIP neurons directly excite interneurons in layers (L)1-3 as well as pyramidal neurons in L2/3 and L6 by fast cholinergic transmission. Dual recordings of presynaptic ChAT-VIP neurons and postsynaptic L1 interneurons show fast nicotinic receptor currents strictly time-locked to single presynaptic action potentials. 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, but instead depolarized fast spiking and low threshold spiking interneurons. Finally, we find that ChAT-VIP neurons control attention behaviour distinctly from basal forebrain ACh inputs to mPFC. Our findings show that ChAT-VIP neurons are a local source of cortical ACh, that directly excite pyramidal and interneurons throughout cortical layers.
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One of the four clusters defined by Vip plus Chat expression might correspond to an interneuron type that directly excites layer 1 interneurons and layer 2/3 pyramidal neurons.
“Certain clusters may correspond to newly discovered types; for example, one of the four clusters defined by Vip plus Chat expression might correspond to a type of interneuron that directly excites layer 1 interneurons and layer 2/3 pyramidal neurons (as described in a preprint report)29.”
From The diversity of GABAergic neurons and neural communication elements (2019) · cites this paper as [29]
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References 63 · Cited by 83
- Authors
- Obermayer, J., Luchicchi, A., de Kloet, S. F., Terra, H., Bruinsma, B., Heistek, T. S., Mnie-Filali, O., Kortleven, C., Kroon, T., Jonker, A. J., Khalil, A. J., de Haan, R., Goriounova, N. A., van den Berg, W. D. J., de Kock, C. P. J., Pattij, T., & Mansvelder, H. D.
- Affiliations
- Amsterdam Neuroscience (NL)
- King's College London (GB)
- Corresponding author
- Pattij, Tommy
- Mansvelder, Huibert D.
- ORCID
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2018-11-04
- Volume
- 10
- Issue
- 1
- Pages
- 5280-5280
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6872593
- OpenAlex
- W2990812548
- Cited by
- 83
- References
- 63
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 19 · 2023: 16 · 2022: 12 · 2021: 10 · 2020: 14 · 2019: 1
- FWCI
- 4.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, cc-by)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- VU Research Portal (publishedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- European Commission (EU-H2020, 720270, HORIZON2020, H2020, 785907)
- Agence Nationale de la Recherche (ANR-17-NEU3-0004)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (013-17-001, 720270, 822.02.013, 865.13.002, 785907)
- Horizon 2020 Framework Programme (EU‐H2020, 720270, 785907)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- choline acetyltransferase, vasoactive intestinal peptide, medial prefrontal cortex, cholinergic neurotransmission, acetylcholine, GABAergic inhibition, pyramidal neurons, cortical layers, attention, neocortical interneurons
- MeSH terms
- Acetylcholine, Animals, Attention, Cerebral Cortex, Choline O-Acetyltransferase, Female, Interneurons, Male, Synaptic Transmission, Neurons, Vasoactive Intestinal Peptide, Prefrontal Cortex, Cholinergic Agents, Rats, Mice, 129 Strain
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