Target-specific co-transmission of acetylcholine and GABA from a subset of cortical VIP+ interneurons

Granger, A. J.; Wang, W.; Robertson, K.; El-Rifai, M.; Zanello, A.; Bistrong, K.; Saunders, A.; Chow, B.; Nunez, V.; Gu, C.; Sabatini, B. L.

doi:10.1101/469064

bioRxiv · 10.1101/469064

Target-specific co-transmission of acetylcholine and GABA from a subset of cortical VIP+ interneurons

Granger, A. J.·Wang, W.·Robertson, K.·El-Rifai, M.·Zanello, A.·Bistrong, K.·Saunders, A.·Chow, B.·Nunez, V.·Gu, C.·Sabatini, B. L.

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Abstract

The modulation of cortex by acetylcholine (ACh) is typically thought to originate from long-range projections arising in the basal forebrain. However, a subset of VIP interneurons express ChAT, the synthetic enzyme for ACh, and are a potential local source of cortical ACh. Which neurotransmitters these VIP/ChAT interneurons (VCINs) release is unclear, and which post-synaptic cell types these transmitters target is not known. Using quantitative molecular analysis of VCIN pre-synaptic terminals, we show expression of the molecular machinery to release both ACh and GABA, with ACh release restricted to a subset of boutons. A systematic survey of potential post-synaptic cell types shows that VCINs release GABA primarily onto other inhibitory interneuron subtypes, while ACh neurotransmission is notably sparse, with most ACh release onto layer 1 interneurons and other VCINs. Therefore, VCINs are an alternative source of cortical ACh signaling that supplement GABA-mediated disinhibition with highly targeted excitation through ACh.

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Granger, A. J., Wang, W., Robertson, K., El-Rifai, M., Zanello, A., Bistrong, K., Saunders, A., Chow, B., Nunez, V., Gu, C., Sabatini, B. L.. 2018-11-12. Target-specific co-transmission of acetylcholine and GABA from a subset of cortical VIP+ interneurons. https://doi.org/10.1101/469064

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