Cholesterol modulates presynaptic and postsynaptic properties of excitatory synaptic transmission
| Autor: | Ladislav Vyklicky, Inmaculada M. Gonzalez-Gonzalez, Martin Horak, Dragana Hajdukovic, Jan Krusek, Tereza Smejkalova, Kristyna Skrenkova, Miloslav Korinek |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Postsynaptic Current Presynaptic Terminals Neurophysiology Glutamic Acid lcsh:Medicine B200 Kainate receptor AMPA receptor Neurotransmission Ion channels in the nervous system Hippocampus Receptors N-Methyl-D-Aspartate Synaptic Transmission Article Postsynapse Presynapse 03 medical and health sciences 0302 clinical medicine Postsynaptic potential Synaptic vesicle exocytosis Animals Lipid-storage diseases Receptors AMPA Neurodegeneration Rats Wistar lcsh:Science Cerebral Cortex Neurons Multidisciplinary Chemistry lcsh:R Excitatory Postsynaptic Potentials Rats Cholesterol 030104 developmental biology Synapses Excitatory postsynaptic potential lcsh:Q lipids (amino acids peptides and proteins) Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-18 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Cholesterol is a structural component of cellular membranes particularly enriched in synapses but its role in synaptic transmission remains poorly understood. We used rat hippocampal cultures and their acute cholesterol depletion by methyl-β-cyclodextrin as a tool to describe the physiological role of cholesterol in glutamatergic synaptic transmission. Cholesterol proved to be a key molecule for the function of synapses as its depletion resulted in a significant reduction of both NMDA receptor (NMDAR) and AMPA/kainate receptor-mediated evoked excitatory postsynaptic currents (eEPSCs), by 94% and 72%, respectively. We identified two presynaptic and two postsynaptic steps of synaptic transmission which are modulated by cholesterol and explain together the above-mentioned reduction of eEPSCs. In the postsynapse, we show that physiological levels of cholesterol are important for maintaining the normal probability of opening of NMDARs and for keeping NMDARs localized in synapses. In the presynapse, our results favour the hypothesis of a role of cholesterol in the propagation of axonal action potentials. Finally, cholesterol is a negative modulator of spontaneous presynaptic glutamate release. Our study identifies cholesterol as an important endogenous regulator of synaptic transmission and provides insight into molecular mechanisms underlying the neurological manifestation of diseases associated with impaired cholesterol synthesis or decomposition. |
| Databáze: | OpenAIRE |
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