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

Adam J. Granger, Wengang Wang, Keiramarie Robertson, Mahmoud El-Rifai, Andrea F. Zanello, Karina Bistrong, Arpiar Saunders, Brian W. Chow, Vicente Nuñez, Miguel Turrero García, Corey C. Harwell, Chenghua Gu, Bernardo L. Sabatini

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


The mouse 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 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. 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.

Original languageEnglish (US)
Article numbere57749
Pages (from-to)1-29
Number of pages29
StatePublished - Jul 2020
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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