The effects of the general anesthetic sevoflurane on neurotransmission: an experimental and computational study
Abstract The brain functions can be reversibly modulated by the action of general anesthetics. Despite a wide number of pharmacological studies, an extensive analysis of the cellular determinants of anesthesia at the microcircuits level is still missing. Here, by combining patch-clamp recordings and...
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Nature Portfolio
2021
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oai:doaj.org-article:b605521fc50f44b897eb09fdba87a53c2021-12-02T14:28:22ZThe effects of the general anesthetic sevoflurane on neurotransmission: an experimental and computational study10.1038/s41598-021-83714-y2045-2322https://doaj.org/article/b605521fc50f44b897eb09fdba87a53c2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83714-yhttps://doaj.org/toc/2045-2322Abstract The brain functions can be reversibly modulated by the action of general anesthetics. Despite a wide number of pharmacological studies, an extensive analysis of the cellular determinants of anesthesia at the microcircuits level is still missing. Here, by combining patch-clamp recordings and mathematical modeling, we examined the impact of sevoflurane, a general anesthetic widely employed in the clinical practice, on neuronal communication. The cerebellar microcircuit was used as a benchmark to analyze the action mechanisms of sevoflurane while a biologically realistic mathematical model was employed to explore at fine grain the molecular targets of anesthetic analyzing its impact on neuronal activity. The sevoflurane altered neurotransmission by strongly increasing GABAergic inhibition while decreasing glutamatergic NMDA activity. These changes caused a notable reduction of spike discharge in cerebellar granule cells (GrCs) following repetitive activation by excitatory mossy fibers (mfs). Unexpectedly, sevoflurane altered GrCs intrinsic excitability promoting action potential generation. Computational modelling revealed that this effect was triggered by an acceleration of persistent sodium current kinetics and by an increase in voltage dependent potassium current conductance. The overall effect was a reduced variability of GrCs responses elicited by mfs supporting the idea that sevoflurane shapes neuronal communication without silencing neural circuits.Jonathan MapelliDaniela GandolfiEnrico GiulianiStefano CasaliLuigi CongiAlberto BarbieriEgidio D’AngeloAlbertino BigianiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021) |
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Medicine R Science Q Jonathan Mapelli Daniela Gandolfi Enrico Giuliani Stefano Casali Luigi Congi Alberto Barbieri Egidio D’Angelo Albertino Bigiani The effects of the general anesthetic sevoflurane on neurotransmission: an experimental and computational study |
| description |
Abstract The brain functions can be reversibly modulated by the action of general anesthetics. Despite a wide number of pharmacological studies, an extensive analysis of the cellular determinants of anesthesia at the microcircuits level is still missing. Here, by combining patch-clamp recordings and mathematical modeling, we examined the impact of sevoflurane, a general anesthetic widely employed in the clinical practice, on neuronal communication. The cerebellar microcircuit was used as a benchmark to analyze the action mechanisms of sevoflurane while a biologically realistic mathematical model was employed to explore at fine grain the molecular targets of anesthetic analyzing its impact on neuronal activity. The sevoflurane altered neurotransmission by strongly increasing GABAergic inhibition while decreasing glutamatergic NMDA activity. These changes caused a notable reduction of spike discharge in cerebellar granule cells (GrCs) following repetitive activation by excitatory mossy fibers (mfs). Unexpectedly, sevoflurane altered GrCs intrinsic excitability promoting action potential generation. Computational modelling revealed that this effect was triggered by an acceleration of persistent sodium current kinetics and by an increase in voltage dependent potassium current conductance. The overall effect was a reduced variability of GrCs responses elicited by mfs supporting the idea that sevoflurane shapes neuronal communication without silencing neural circuits. |
| format |
article |
| author |
Jonathan Mapelli Daniela Gandolfi Enrico Giuliani Stefano Casali Luigi Congi Alberto Barbieri Egidio D’Angelo Albertino Bigiani |
| author_facet |
Jonathan Mapelli Daniela Gandolfi Enrico Giuliani Stefano Casali Luigi Congi Alberto Barbieri Egidio D’Angelo Albertino Bigiani |
| author_sort |
Jonathan Mapelli |
| title |
The effects of the general anesthetic sevoflurane on neurotransmission: an experimental and computational study |
| title_short |
The effects of the general anesthetic sevoflurane on neurotransmission: an experimental and computational study |
| title_full |
The effects of the general anesthetic sevoflurane on neurotransmission: an experimental and computational study |
| title_fullStr |
The effects of the general anesthetic sevoflurane on neurotransmission: an experimental and computational study |
| title_full_unstemmed |
The effects of the general anesthetic sevoflurane on neurotransmission: an experimental and computational study |
| title_sort |
effects of the general anesthetic sevoflurane on neurotransmission: an experimental and computational study |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/b605521fc50f44b897eb09fdba87a53c |
| work_keys_str_mv |
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