Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner
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+ neuron...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/57749 |
| _version_ | 1811236803210903552 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Adam J Granger |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T12:15:32Z |
| format | Article |
| id | doaj.art-46e08e2f33a545e3a225aa162a807d44 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:15:32Z |
| publishDate | 2020-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-46e08e2f33a545e3a225aa162a807d442022-12-22T03:33:27ZengeLife Sciences Publications LtdeLife2050-084X2020-07-01910.7554/eLife.57749Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific mannerAdam J Granger0https://orcid.org/0000-0002-3953-6764Wengang Wang1Keiramarie Robertson2Mahmoud El-Rifai3Andrea F Zanello4Karina Bistrong5Arpiar Saunders6Brian W Chow7Vicente Nuñez8Miguel Turrero García9https://orcid.org/0000-0002-7294-169XCorey C Harwell10Chenghua Gu11https://orcid.org/0000-0002-4212-7232Bernardo L Sabatini12https://orcid.org/0000-0003-0095-9177Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, United StatesHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, United StatesHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, United StatesNeurobiology Imaging Facility, Department of Neurobiology, Harvard Medical School, Boston, United StatesHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, United StatesHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Genetics, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, United StatesThe 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.https://elifesciences.org/articles/57749neuromodulationneurotransmitter co-releaseAcetylcholineGABAVIPcortical interneurons |
| spellingShingle | 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 Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner eLife neuromodulation neurotransmitter co-release Acetylcholine GABA VIP cortical interneurons |
| title | Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner |
| title_full | Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner |
| title_fullStr | Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner |
| title_full_unstemmed | Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner |
| title_short | Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner |
| title_sort | cortical chat neurons co transmit acetylcholine and gaba in a target and brain region specific manner |
| topic | neuromodulation neurotransmitter co-release Acetylcholine GABA VIP cortical interneurons |
| url | https://elifesciences.org/articles/57749 |
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