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.
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http://dx.doi.org/10.7554/eLife.57749 | DOI Listing |
eNeuro
December 2024
Departamento de Fisiología y Biofísica, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí 78210, México
Autism spectrum disorder (ASD) is characterized by deficits in social interaction and communication, cognitive rigidity, and atypical sensory processing. Recent studies suggest that the basal ganglia, specifically the striatum (NSt), plays an important role in ASD. While striatal interneurons, including cholinergic (ChAT) and parvalbumin-positive (PV) GABAergic neurons, have been described to be altered in animal models of ASD, their specific contribution remains elusive.
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November 2024
Department of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Front Endocrinol (Lausanne)
November 2024
Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
PLoS One
October 2024
Department of Psychology, Behavioral Neuroscience Area, Binghamton University-State University of New York, Binghamton, NY, United States of America.
Adolescent intermittent ethanol (AIE) exposure, which models heavy binge ethanol intake in adolescence, leads to a variety of deficits that persist into adulthood-including suppression of the cholinergic neuron phenotype within the basal forebrain. This is accompanied by a reduction in acetylcholine (ACh) tone in the medial prefrontal cortex (mPFC). Voluntary wheel running exercise (VEx) has been shown to rescue AIE-induced suppression of the cholinergic phenotype.
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October 2024
Institut de Biologie de l'ENS (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, 75005 Paris, France. Electronic address:
Human-specific genes are potential drivers of brain evolution. Among them, SRGAP2C has contributed to the emergence of features characterizing human cortical synapses, including their extended period of maturation. SRGAP2C inhibits its ancestral copy, the postsynaptic protein SRGAP2A, but the synaptic molecular pathways differentially regulated in humans by SRGAP2 proteins remain largely unknown.
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