The role of neocortical neurons on general anesthesia

Volatile and intravenous general anesthetics encompass a diverse array of small and uncharged chemotypes including haloalkanes, haloethers, and alkylphenols. Despite efforts reaching back over a century, clarification of their action mechanism has proven difficult and wanting. A favored hypothesis proposes that ion channels in the brain are implicated, among which members of ionotropic neurotransmitter receptors, voltage-gated and non-gated ion channels are best-known players. At the cellular level, mounting evidence supports that neocortical neurons synchronize their firing activity during various forms of general anesthesia, including loss and recovery of consciousness. Neocortical neurons, including interneurons, are therefore critical cellular targets for general anesthetics, largely implicated in one or more general anesthesia outcomes.
The study of volatile anesthetics is particularly intriguing due to their capacity to impair interactions with the external environment across a vast array of life forms. The widespread impact of volatile anesthetics on various organisms implies a more fundamental mechanism of action, potentially involving multiple neuronal targets and their membrane-embedded proteins, such as neurotransmitter receptors and ion channels. Novel experiments targeting the cellular action of general anesthetics across different areas of the central nervous are therefore timely and urgent. Of particular interest is the action mechanism of general anesthetics on neocortical neurons, for which excitability changes, involving synchronized firing activity, largely correlates with hallmarks of anesthesia, including loss and recovery of consciousness. As a paradigm shift in our current view, the modulation of the collective firing of neocortical neurons by general anesthetics is expected to be critical for anesthesia, opening new directions of research towards the molecular/cellular mechanism by which anesthetics work.
In this Research Topic, Frontiers in Cellular Neuroscience is looking to address key aspects of “The role of neocortical neurons on general anesthesia” in order to promote the discussion around this topic and to facilitate knowledge dissemination. We particularly welcome submission of original research articles, forward thinking reviews, hypothesis and theory and opinion articles, new methods and perspective articles including, but not limited to, the following sub-topics:
• Molecular targets for general anesthetics: composition and cellular localization in neocortical neurons
• Molecular mechanism of general anesthetics in neocortical neurons
• Modulation of neocortical neurons by general anesthetics and implications for anesthesia outcomes, including loss and recovery of consciousness, sleep, memory loss and paralysis
• Selective modulation of cellular subtypes of neocortical neurons by general anesthetics
• The role of inhibitory interneurons on general anesthesia
• Molecular basis for synchronized activity of neocortical neurons and implications for general anesthesia

Keywords: general anesthetics, ion channels, neocortical neurons, inhibitory interneurons, synchronized activity, loss and recovery of consciousness

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