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

Joshua Obermayer; Antonio Luchicchi; Tim S. Heistek; Sybren F. de Kloet; Huub Terra; Bastiaan Bruinsma; Ouissame Mnie-Filali; Christian Kortleven; Anna A. Galakhova; Ayoub J. Khalil; Tim Kroon; Allert J. Jonker; Roel de Haan; Wilma D.J. van den Berg; Natalia A. Goriounova; Christiaan P.J. de Kock; Tommy Pattij; Huibert D. Mansvelder

doi:10.1038/s41467-019-13244-9

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

Joshua Obermayer
, Antonio Luchicchi
, Tim S. Heistek
, Sybren F. de Kloet
, Huub Terra
, Bastiaan Bruinsma
, Ouissame Mnie-Filali
, Christian Kortleven
, Anna A. Galakhova
, Ayoub J. Khalil
, Tim Kroon
, Allert J. Jonker
, Roel de Haan
, Wilma D.J. van den Berg
, Natalia A. Goriounova
, Christiaan P.J. de Kock
, Tommy Pattij
, Huibert D. Mansvelder^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

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.

Original language	English
Article number	5280
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13244-9
Publication status	Published - 1 Dec 2019

Funding

We thank J.N. Vaiña, MSc, for excellent technical assistance, and Dr. K. Deisseroth for the generous sharing of tools and ChAT-cre rats. H.D.M. received funding for this work from the Netherlands Organization for Scientific Research (NWO; VICI grant 865.13.002), ERC StG “BrainSignals,” EU H2020 Framework Programme (Grant Agreement H2020 HBP 720270), and European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 785907 (Human Brain Project SGA2) and EraNet Neuron/NWO. C.P.J.d.K. received funding for this work from the Netherlands Organization for Scientific Research (NWO ALW #822.02.013).

Funders	Funder number
EraNet Neuron/NWO
Netherlands Organization for Scientific Research
Seventh Framework Programme
European Commission
NWO ALW
H2020 European Research Council
ERC StG
Horizon 2020 Framework Programme	SGA2, 785907, 281443, 720270
???publication-publication-funding-organisation-not-added???	822.02.013
EU H2020 Framework Programme	H2020 HBP 720270
VICI	865.13.002

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/s41467-019-13244-9

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Obermayer, J., Luchicchi, A., Heistek, T. S., de Kloet, S. F., Terra, H., Bruinsma, B., Mnie-Filali, O., Kortleven, C., Galakhova, A. A., Khalil, A. J., Kroon, T., Jonker, A. J., de Haan, R., van den Berg, W. D. J., Goriounova, N. A., de Kock, C. P. J., Pattij, T., & Mansvelder, H. D. (2019). Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention. Nature Communications, 10(1), Article 5280. https://doi.org/10.1038/s41467-019-13244-9

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

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.",

author = "Joshua Obermayer and Antonio Luchicchi and Heistek, \{Tim S.\} and \{de Kloet\}, \{Sybren F.\} and Huub Terra and Bastiaan Bruinsma and Ouissame Mnie-Filali and Christian Kortleven and Galakhova, \{Anna A.\} and Khalil, \{Ayoub J.\} and Tim Kroon and Jonker, \{Allert J.\} and \{de Haan\}, Roel and \{van den Berg\}, \{Wilma D.J.\} and Goriounova, \{Natalia A.\} and \{de Kock\}, \{Christiaan P.J.\} and Tommy Pattij and Mansvelder, \{Huibert D.\}",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-13244-9",

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Obermayer, J, Luchicchi, A, Heistek, TS, de Kloet, SF, Terra, H, Bruinsma, B, Mnie-Filali, O, Kortleven, C, Galakhova, AA, Khalil, AJ, Kroon, T, Jonker, AJ, de Haan, R, van den Berg, WDJ, Goriounova, NA , de Kock, CPJ, Pattij, T & Mansvelder, HD 2019, 'Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention', Nature Communications, vol. 10, no. 1, 5280. https://doi.org/10.1038/s41467-019-13244-9

TY - JOUR

T1 - Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention

AU - Obermayer, Joshua

AU - Luchicchi, Antonio

AU - Heistek, Tim S.

AU - de Kloet, Sybren F.

AU - Terra, Huub

AU - Bruinsma, Bastiaan

AU - Mnie-Filali, Ouissame

AU - Kortleven, Christian

AU - Galakhova, Anna A.

AU - Khalil, Ayoub J.

AU - Kroon, Tim

AU - Jonker, Allert J.

AU - de Haan, Roel

AU - van den Berg, Wilma D.J.

AU - Goriounova, Natalia A.

AU - de Kock, Christiaan P.J.

AU - Pattij, Tommy

AU - Mansvelder, Huibert D.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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UR - https://www.scopus.com/pages/publications/85075395769#tab=citedBy

U2 - 10.1038/s41467-019-13244-9

DO - 10.1038/s41467-019-13244-9

M3 - Article

C2 - 31754098

AN - SCOPUS:85075395769

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5280

ER -

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

Abstract

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