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bioRxiv · 10.1101/2020.04.20.051276

Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region specific manner

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.
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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.

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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.. 2020-04-21. Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region specific manner. https://doi.org/10.1101/2020.04.20.051276

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