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Line 27: − *'''Are there model organisms (or can we make them) with optogenetic activation or inhibition of anesthetic receptors?'''
→Mechanisms of Anesthesia
*Some anesthetics ('''ketamine, dexmedetomidine, etomidate, benzos''') are fairly selective, but are rarely used as sole anesthetics.
*Some anesthetics ('''ketamine, dexmedetomidine, etomidate, benzos''') are fairly selective, but are rarely used as sole anesthetics.
*[https://scholar.googleusercontent.com/scholar.bib?q=info:dK96wvRnWFAJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixESwUs:ACTRDVEAAAAAasUU2UsAEqSgPmvYJRTMHcZKb4s&scisig=ACTRDVEAAAAAasUU2a34RqVYzDaWRdbVsL76Mk4&scisf=4&ct=citation&cd=-1&hl=en 2026 A&A paper] argues that classifying anesthetics as, say, GABAergic vs. NMDAergic is misleading. Propofol for instance actually has higher potency at the α4β2 nAChR and HCN1 receptors than at the "classic" GABA<sub>A</sub>R receptor.
*[https://scholar.googleusercontent.com/scholar.bib?q=info:dK96wvRnWFAJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixESwUs:ACTRDVEAAAAAasUU2UsAEqSgPmvYJRTMHcZKb4s&scisig=ACTRDVEAAAAAasUU2a34RqVYzDaWRdbVsL76Mk4&scisf=4&ct=citation&cd=-1&hl=en 2026 A&A paper] argues that classifying anesthetics as, say, GABAergic vs. NMDAergic is misleading. Propofol for instance actually has higher potency at the α4β2 nAChR and HCN1 receptors than at the "classic" GABA<sub>A</sub>R receptor.
*What if you found pharmacological inhibitors that were receptor specific and gave them together with "promiscuous" anesthetics. For instance, is propofol equally effective when given with a specific HCN1 receptor inhibitor? What about a GABA<sub>A</sub>R inhibitor? Could you do optogenetic location-specific receptor knockdowns?
*'''Are there pharmacological inhibitors with receptor specificity? When given together with "promiscuous" anesthetics, what happens? For instance, is propofol equally effective when given with a specific HCN1 receptor inhibitor? What about a GABA<sub>A</sub>R inhibitor? Could you do optogenetic location-specific inducible receptor knockdowns? Do model organisms already exist?'''
*Hamilton has a gap junction (network of gap junctions?) and some specific neurons that he think are a conserved mechanism of anesthesia. He wants to test this by doing a screen of a bunch of different anesthetics in WT and KO worms with a behavioral screening assay. He has a behavior rig that basically automatically records swimming speed. He wants to look for the EC50 of various anesthetics and see if that number is shifted with KO or KD of different gap junctions.
*Hamilton has a gap junction (network of gap junctions?) and some specific neurons that he think are a conserved mechanism of anesthesia. He wants to test this by doing a screen of a bunch of different anesthetics in WT and KO worms with a behavioral screening assay. He has a behavior rig that basically automatically records swimming speed. He wants to look for the EC50 of various anesthetics and see if that number is shifted with KO or KD of different gap junctions.
*Worms natively have a blue-light rhodopsin that triggers an aversion response where they turn around and go the opposite direction.
*Worms natively have a blue-light rhodopsin that triggers an aversion response where they turn around and go the opposite direction.
*Big picture: understand the temporospatial changes in neural activity induced by various anesthetics. Can we recapitulate those with steerable, low latency, closed-loop non-invasive neuromodulation?
*Big picture: understand the temporospatial changes in neural activity induced by various anesthetics. Can we recapitulate those with steerable, low latency, closed-loop non-invasive neuromodulation?
*What are the differences in mechanisms for amnesia, hypnosis, immobility, and analgesia?
*What are the differences in mechanisms for amnesia, hypnosis, immobility, and analgesia?
===CLAN===
===CLAN===