Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target-and brain-region specific manner
- Howard Hughes Medical Institute, Harvard Medical School, United States
- Harvard Medical School, United States
Abstract
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.
Data availability
All data generated during this study are summarized in the figures and supporting files of this manuscript. Source data files from which the figures were generated are available at: https://dataverse.harvard.edu/dataset.xhtml?persistentId=doi:10.7910/DVN/AIUTNJ
Article and author information
Author details
Miguel Turrero García
Bernardo L Sabatini
Funding
National Institute of Neurological Disorders and Stroke (R37 NS046579)
- Bernardo L Sabatini
National Institute of Neurological Disorders and Stroke (K99 NS102429)
- Adam J Granger
National Institute of Neurological Disorders and Stroke (P30Ns072030)
- Mahmoud El-Rifai
Jane Coffin Childs Memorial Fund for Medical Research
- Adam J Granger
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the NIH, and according to strict adherence to the protocols approved by the Institutional Animal Care and Use Committee (IACUC) of Harvard Medical School (protocol #IS00000571). Routine examination, veterinary care, disease surveillance, and animal use compliance were all carried out by certified veterinary staff of the Harvard Center for Comparative Medicine (HCCM) in addition to full daily animal husbandry provided by trained animal technicians.
Copyright
© 2020, Granger et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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