Changes

*Downsides of using 'weird' organisms is that there are relatively few genetic tools, antibodies, sparse literature, and few experts to consult.

*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?

*Has anyone published behavioral assays for these organisms? Detailed protocols for breeding them? Have they already been anesthetized?

 

*[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_AR 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_AR 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.

*According to this paper, some anesthetics (i.e. ketamine, dexmedetomidine, etomidate, benzos) are fairly selective, but are rarely used as sole anesthetics. Below, I list each of the ''in vitro'' binding affinities of these "selective" anesthetics, up until there is a change of one order of magnitude or greater for the next receptor.

*According to this paper, some anesthetics (i.e. ketamine, dexmedetomidine, etomidate, benzos) are fairly selective, but are rarely used as sole anesthetics. Below, I list each of the ''in vitro'' binding affinities of these "selective" anesthetics, up until there is a change of one order of magnitude or greater for the next receptor.

*Remimazolam binds GABA_A receptors [https://scholar.googleusercontent.com/scholar.bib?q=info:ZcRExfhIAgQJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixJ14Lg:ACTRDVEAAAAAasZz-Lg_XypnrGdHd1YvgyClzzA&scisig=ACTRDVEAAAAAasZz-GKPI-Z0ueEzxZoNZQpLFsU&scisf=4&ct=citation&cd=-1&hl=en non-selectively] (i.e. αxβ2γ2)

*Remimazolam binds GABA_A receptors [https://scholar.googleusercontent.com/scholar.bib?q=info:ZcRExfhIAgQJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixJ14Lg:ACTRDVEAAAAAasZz-Lg_XypnrGdHd1YvgyClzzA&scisig=ACTRDVEAAAAAasZz-GKPI-Z0ueEzxZoNZQpLFsU&scisf=4&ct=citation&cd=-1&hl=en non-selectively] (i.e. αxβ2γ2)

*Propofol binds to α4β2 nAChR with IC₅₀ of 3.13 uM, HCN1 receptors with IC₅₀ of 4.19 uM, and α1β2γ2 with EC₅₀ of 5.44 uM.

*Propofol binds to α4β2 nAChR with IC₅₀ of 3.13 uM, HCN1 receptors with IC₅₀ of 4.19 uM, and α1β2γ2 with EC₅₀ of 5.44 uM.

*'''Are there pharmacological agents with effects opposite of anesthetics and with receptor specificity? Do they cross the blood brain barrier? Search [https://www.ebi.ac.uk/chembl/explore/compound/CHEMBL63354/ ChEMBL].'''

*'''Are there pharmacological agents with effects opposite of anesthetics and with receptor specificity? Do they cross the blood brain barrier? Search [https://www.ebi.ac.uk/chembl/explore/compound/CHEMBL63354/ ChEMBL].'''

{| class="wikitable sortable"

{| class="wikitable sortable"

**'''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?'''

*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.