Unfortunately, the physiology and function of these cells are poorly understood and their contribution to cortical signal has been controversial. However, cholinergic interneurons are present in the cortex of mice and rats and could provide a local source of ACh. Most cortical ACh originates from subcortical nuclei in the basal forebrain Mesulam, 1995 whose long-range axons innervate broad regions of cortex and release ACh to modulate cortical function over fast and slow time scales ( Sarter et al., 2009 Picciotto et al., 2012). IntroductionĪcetylcholine (ACh) is a neurotransmitter and neuromodulator that is released throughout the mammalian cortex at times of alertness and arousal ( Teles-Grilo Ruivo et al., 2017) in order to promote learning and memory ( Hasselmo, 2006), modulate sensory perception ( Pinto et al., 2013), gate plasticity ( Morishita et al., 2010 Rasmusson, 2000), and enhance the detection of salient sensory cues and reinforcement ( Parikh et al., 2007 Sarter et al., 2009 Sarter et al., 2014 Sturgill et al., 2020). These results demonstrate both cortex-region heterogeneity in cortical ChAT + interneurons and target-specific co-release of acetylcholine and GABA. In addition, we identify a separate, sparse population of non-VIP ChAT + neurons in the medial prefrontal cortex with a distinct developmental origin that robustly release acetylcholine in layer 1. This differential transmission of ACh and GABA based on the postsynaptic target neuron is reflected in VIP +/ChAT + interneuron pre-synaptic terminals, as quantitative molecular analysis shows that only a subset of these are specialized to release acetylcholine.

We show that the nearly all cortical ChAT + neurons in mice are specialized VIP + interneurons that release GABA strongly onto other inhibitory interneurons and acetylcholine sparsely onto layer 1 interneurons and other VIP +/ChAT + interneurons. However, the neurotransmitters released by cortical ChAT + neurons and their synaptic connectivity are unknown. The mouse cerebral cortex contains neurons that express choline acetyltransferase (ChAT) and are a potential local source of acetylcholine.

Wavesurfer regions annotations