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→Mechanisms of Anesthesia
==Mechanisms of Anesthesia==
==Mechanisms of Anesthesia==
*High-throughput screen of anesthetics (and anesthetic reversal agents) in ''C.elegans''. I could work in parallel in a different organism (e.g. yeast, jellyfish, hydra, sea anemones, corral, bacteria, plants, neuronal explants).
*High-throughput screen of anesthetics (and anesthetic reversal agents) in ''C.elegans''.
===Promiscuous Molecular Targets===
===Promiscuous Molecular Targets===
*[https://scholar.googleusercontent.com/scholar.bib?q=info:dK96wvRnWFAJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixJyYaI:ACTRDVEAAAAAasZ0eaKpU14jFRxgeJubQZ-AUJs&scisig=ACTRDVEAAAAAasZ0eT0zDfaBVoegO8FEa7bX0-A&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. Based on 30 years of in vitro studies (n>330), most anesthetics exhibit similar potency across a range of receptors. Most receptors are non-selective for ligands. What this paper addresses but doesn't answer is whether the receptors are present at the correct locations and necessary to the anesthetic behavioral response.
*[https://scholar.googleusercontent.com/scholar.bib?q=info:dK96wvRnWFAJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixJyYaI:ACTRDVEAAAAAasZ0eaKpU14jFRxgeJubQZ-AUJs&scisig=ACTRDVEAAAAAasZ0eT0zDfaBVoegO8FEa7bX0-A&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. Based on 30 years of in vitro studies (n>330), most anesthetics exhibit similar potency across a range of receptors. Most receptors are non-selective for ligands. What this paper addresses but doesn't answer is whether the receptors are present at the correct locations and necessary to the anesthetic behavioral response.
**'''Search [https://flybase.org flybase], [https://www.informatics.jax.org/ MGI], [https://www.wormbase.org/ wormbase], [https://zfin.org/ zebra fish information network], [https://www.yeastgenome.org/ yeast genome database]'''
**'''Search [https://flybase.org flybase], [https://www.informatics.jax.org/ MGI], [https://www.wormbase.org/ wormbase], [https://zfin.org/ zebra fish information network], [https://www.yeastgenome.org/ yeast genome database]'''
*'''Where and by what cell types are these receptors expressed in the human brain?'''
*'''Where and by what cell types are these receptors expressed in the human brain?'''
====Phylogenetic Approach====
*Are there organisms that are resistant to anesthetics? Search for 'weird' organisms that might yield something interesting. Prokaryotes (bacteria, archaea) and Eukaryotes (Protists, Plants, Animals, Fungi). Single cellular and multicellular organisms. What is different about them?
**Downsides of using 'weird' organisms is that there are relatively few genetic tools, antibodies, sparse literature, and few experts to consult.
**Has anyone published behavioral assays for these organisms? Detailed protocols for breeding them? Have they already been anesthetized?
===Non Receptor-Mediated Hypothesis===
===Non Receptor-Mediated Hypothesis===