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

SummaryNeocortical 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.