Co-transmission of acetylcholine and GABA regulates hippocampal states
| Autor: | Attila I. Gulyás, Zsuzsanna Környei, Gábor Nyiri, Virág T. Takács, Dániel Schlingloff, Katalin E. Sos, Adam Denes, Csaba Cserép, Tamás F. Freund, Balázs Pósfai, András Szonyi |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Science General Physics and Astronomy Hippocampal formation Neurotransmission Hippocampus Synaptic Transmission Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences chemistry.chemical_compound Imaging Three-Dimensional 0302 clinical medicine Postsynaptic potential medicine Animals Neurotransmitter lcsh:Science gamma-Aminobutyric Acid Neurotransmitter Agents Basal forebrain Multidisciplinary Neurodegenerative Diseases Dendrites General Chemistry Synaptic Potentials Receptors GABA-A Acetylcholine Mice Inbred C57BL Perfusion 030104 developmental biology chemistry Synapses Cholinergic GABAergic Calcium Female lcsh:Q Synaptic Vesicles Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-15 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-05136-1 |
| Popis: | The basal forebrain cholinergic system is widely assumed to control cortical functions via non-synaptic transmission of a single neurotransmitter. Yet, we find that mouse hippocampal cholinergic terminals invariably establish GABAergic synapses, and their cholinergic vesicles dock at those synapses only. We demonstrate that these synapses do not co-release but co-transmit GABA and acetylcholine via different vesicles, whose release is triggered by distinct calcium channels. This co-transmission evokes composite postsynaptic potentials, which are mutually cross-regulated by presynaptic autoreceptors. Although postsynaptic cholinergic receptor distribution cannot be investigated, their response latencies suggest a focal, intra- and/or peri-synaptic localisation, while GABAA receptors are detected intra-synaptically. The GABAergic component alone effectively suppresses hippocampal sharp wave-ripples and epileptiform activity. Therefore, the differentially regulated GABAergic and cholinergic co-transmission suggests a hitherto unrecognised level of control over cortical states. This novel model of hippocampal cholinergic neurotransmission may lead to alternative pharmacotherapies after cholinergic deinnervation seen in neurodegenerative disorders. Acetylcholine (ACh) release in the central nervous system is thought to be unitary and mediated non-synaptically in volume transmission. Here, Takács and colleagues show cholinergic terminals juxtapose GABAergic synapses anatomically and functionally, and GABA and ACh molecules are co-transmitted. |
| Databáze: | OpenAIRE |
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