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.

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.

Details

Title
Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention
Author
Obermayer, Joshua 1 ; Luchicchi Antonio 2 ; Heistek, Tim S 1 ; de Kloet Sybren F 1 ; Terra Huub 1 ; Bruinsma Bastiaan 1 ; Mnie-Filali Ouissame 1 ; Kortleven Christian 1 ; Galakhova, Anna A 1   VIAFID ORCID Logo  ; Khalil, Ayoub J 1 ; Kroon, Tim 3   VIAFID ORCID Logo  ; Jonker, Allert J 4 ; de Haan Roel 1   VIAFID ORCID Logo  ; van de Berg Wilma D J 4   VIAFID ORCID Logo  ; Goriounova, Natalia A 1   VIAFID ORCID Logo  ; de Kock Christiaan P J 1 ; Pattij Tommy 4   VIAFID ORCID Logo  ; Mansvelder, Huibert D 1   VIAFID ORCID Logo 

1  Vrije Universiteit, Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) 
2  Vrije Universiteit, Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227); Vrije Universiteit, Department of Anatomy and Neurosciences, Clinical Neuroscience, Amsterdam UMC, Amsterdam Neuroscience, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) 
3  Vrije Universiteit, Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227); MRC Centre-Developmental Neurobiology, King’s College London, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764) 
4  Vrije Universiteit, Department of Anatomy and Neurosciences, Amsterdam UMC, Amsterdam Neuroscience, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) 
Publication year
2019
Publication date
Nov 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-13244-9
ProQuest document ID
2316782039
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.