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

Joshua Obermayer, Antonio Luchicchi, Tim S. Heistek, Sybren F. Kloet, Huub Terra, Bastiaan Bruinsma, Ouissame Mnie-Filali, Christian Kortleven, Anna A. Galakhova, Ayoub J. Khalil, Tim Kroon, Allert J. Jonker, Roel Haan, Wilma D. J. Berg, Natalia A. Goriounova, Christiaan P. J. Kock, Tommy Pattij () and Huibert D. Mansvelder ()
Additional contact information
Joshua Obermayer: Vrije Universiteit
Antonio Luchicchi: Vrije Universiteit
Tim S. Heistek: Vrije Universiteit
Sybren F. Kloet: Vrije Universiteit
Huub Terra: Vrije Universiteit
Bastiaan Bruinsma: Vrije Universiteit
Ouissame Mnie-Filali: Vrije Universiteit
Christian Kortleven: Vrije Universiteit
Anna A. Galakhova: Vrije Universiteit
Ayoub J. Khalil: Vrije Universiteit
Tim Kroon: Vrije Universiteit
Allert J. Jonker: Vrije Universiteit
Roel Haan: Vrije Universiteit
Wilma D. J. Berg: Vrije Universiteit
Natalia A. Goriounova: Vrije Universiteit
Christiaan P. J. Kock: Vrije Universiteit
Tommy Pattij: Vrije Universiteit
Huibert D. Mansvelder: Vrije Universiteit

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13244-9

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