Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.20.051276v1?rss=1 Authors: Granger, A. J., Wang, W., Robertson, K., El-Rifai, M., Zanello, A. F., Bistrong, K., Saunders, A., Chow, B. W., Nunez, V., Turrero Garcia, M., Harwell, C. C., Gu, C., Sabatini, B. L. Abstract: The cerebral cortex contains neurons that express choline acetyltransferase (ChAT) and are a potential local source of acetylcholine. However, the neurotransmitters released by cortical ChAT+ neurons and their synaptic connectivity are unknown. We show that the nearly all cortical ChAT+ neurons are specialized VIP+ interneurons that release GABA strongly onto other inhibitory interneurons and acetylcholine sparsely onto layer 1 interneurons and other VIP+/ChAT+ interneurons. 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. 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. These results demonstrate both cortex-region heterogeneity in cortical ChAT+ interneurons and target-specific co-release of acetylcholine and GABA. Copy rights belong to original authors. Visit the link for more info