RT Journal Article SR Electronic T1 Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention JF bioRxiv FD Cold Spring Harbor Laboratory SP 461723 DO 10.1101/461723 A1 Joshua Obermayer A1 Antonio Luchicchi A1 Sybren F. de Kloet A1 Huub Terra A1 Bastiaan Bruinsma A1 Tim S. Heistek A1 Oissame Mnie-Filali A1 Christian Kortleven A1 Tim Kroon A1 Allert J. Jonker A1 Ayoub J. Khalil A1 Roel de Haan A1 Natalia A. Goriounova A1 Wilma D.J. van den Berg A1 Christiaan P.J. de Kock A1 Tommy Pattij A1 Huibert D. Mansvelder YR 2018 UL http://biorxiv.org/content/early/2018/11/04/461723.abstract 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. 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.