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Line 32: − + − **'''What are MER transitions?'''+ − + − **Trying to figure out frequency and phase response of the SedLine+ − **Some seriously impressive GUIs+ − + − *Call w/ Christian+ − **Christian has Wednesday/Thursday off every week, his third NCD is variable.+ − **Christian to add me to two protocols for collecting human EEG data+ − ***SedLine deferred consent retrospective study (PI is Norm Taylor)+ − + − **[https://www.tidalneuro.com/# TidalNeuro] is the start-up and we are developing Ripple-grade wireless device+ − − **GitHub can pull functions to work on data from the web disk. Srdjan added me to the main branch. − − − **Meet next Tuesday to demo Ripple hardware with live intra-op recordings. − **EEG workshop at February meeting. Christian shared 16 PEACE competencies to start prepping. We could either split it up to each do 8 (preferable), or we could cover all 16, but on different devices. − − − − − **'''Read all about GABA receptors in Principles of Neural Science''' − **Optogenetics can control the activity of a genetically defined set of neurons to see if they are important for your topic of interest. e.g. express anion-conducting channelrhodopsins (ACRs, an inhibitory type of ChR) in α1β2γ2 GABA-R expressing neurons. − − − ## Excitatory cortical pyramidal neurons − ## Galan-/GABA-ergic hypothalamic POA projections to monoaminergic brainstem nuclei: LC (NE), DR (5HT), vPAG (DA), TMN (His) − ## GABAergic neurons in the TRN (thalamic reticular nucleus) − − * Who is doing patch clamp that could teach me or just do it? Coby has experience with ephys. − − − ** His lab specializes in light-sheet imaging and they have single neuron resolution where they can look at calcium currents (neuronal activity) in real time. − ** He mentioned that ''C. elegans'' don't have any histamine signaling natively. You can make animals that express histamine-gated chloride channels to inactivate channel expressing neurons when histamine is given exogenously. '''Look for a GABA<sub>A</sub>R His-Cl worm line. − ** He is going to send me some links to worm genetic databases, and some protocols for breeding and behavior. − ** I am going to read up on propofol mechanisms '''in worms''', and gap junctions before our next meeting on 10/29. − *IARS abstract submission deadline is 12/6 (methohexital, ketamine depression, SCD-PV)+ − + − *** Talk to a circulator/scrub RN with a lot of experience.+ − + − *** How long have we had that one model? What did we use before that?+ − *** Do the RNs track anywhere that the boots have been applied and to which legs? − − Line 102:
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no edit summary
==10/14 Summary==
==10/14 Summary==
*Lab meeting
*Attended SandLab meeting ('''What are MER transitions?'''
*Called Christian (consistently has Wed/Thu off, added me to two IRB protocols after I uploaded CITI competency to ERICA system)
**'''DECODE problem is how to detect neural activity of subcortical sources from scalp EEG?''' They are currently throwing different things at it but from a single EEG electrode.
*COMPASS protocol we do need to consent patients (what is it?)
*Cameron Jacobson added access to local SAND lab web disk. ('''Need to figure out how to connect to VPN''')
*GitHub can pull functions to work on data from the web disk. Srdjan added me to the main branch. '''Still need to figure out how to clone the repository'''
*Kristen Kinjo added me to her list to inform of possible funding opportunities.
*Discussed EEG workshop at February meeting. Christian shared 16 PEACE competencies to start prepping.
*Reached out to Grace about ketamine research
*Thought about how to probe propofol mechanisms (opto/chemogenetics, pharmacological approaches)
*Met with Hamilton
***DECODE (neurosurgery, SEEG-electrodes, LFP along the whole lead, individual neurons at the tips), neuromodulation using Ripple (lab-grade, non-FDA approved device), different protocol (COMPASS) where we do need to consent patients
*Coby has experience with ephys, might be able to teach patch clamp.
*IARS abstract submission deadline is 12/6 (methohexital, ketamine depression, SCD-PV)
**Need access to files. Figure out how to connect to VPN. Cameron Jacobson added access to local SAND lab web disk.
**FAER, IARS, RISE. Kristen Kinjo added me to her list to inform of possible funding opportunities.
**Uploaded CITI competency to ERICA system, CC'd Christian
*Reached out to Grace about ketamine research (OB vs. general surgery population, decreasing incidence of postpartum/post-op depression w/ single dose of ketamine).
*Thinking about propofol mechanisms
***Could we use optogenetics to clarify whether certain non-canonical propofol target receptors (e.g. α4β2 nAChR, HCN1) are necessary or sufficient for its effects?
***Assuming that α1β2γ2 GABA<sub>A</sub>R is the critical receptor, can we demonstrate which circuits play a critical role? As a starting point (from Brown's Part I):
* Meeting with Hamilton
==10/20 Summary==
** SCD PV
*Reached out to Houman re: Methohexital data.
*Figured out software and access (web disk, GitHub repos, EEGLAB, MatLab, Anaconda)
*** Do we only have one model?
*Demoed BATMAN hardware with Christian in the OR
*Met w/ Amy
*** Where in the flowsheets is last liquid intake listed?
** '''Methohexital'''
==Mechanisms of Anesthesia==
==Mechanisms of Anesthesia==
*Some common anesthetics that are less selective, or not characterized in the paper
*Some common anesthetics that are less selective, or not characterized in the paper
**Propofol binds to α4β2 nAChR with IC<sub>50</sub> of 3.13 uM, HCN1 receptors with IC<sub>50</sub> of 4.19 uM, and α1β2γ2 with EC<sub>50</sub> of 5.44 uM.
**Propofol binds to α4β2 nAChR with IC<sub>50</sub> of 3.13 uM, HCN1 receptors with IC<sub>50</sub> of 4.19 uM, and α1β2γ2 with EC<sub>50</sub> of 5.44 uM.
***'''Read all about GABA receptors in Principles of Neural Science'''
**Remimazolam binds GABA<sub>A</sub> 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<sub>A</sub> 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)
====Rx Probing Anesthetic-Receptor Interactions====
====Rx Probing Anesthetic-Receptor Interactions====
*'''Are there pharmacological agents with effects complementary to those of anesthetics 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 complementary to those of anesthetics with receptor specificity? Do they cross the blood brain barrier? Search [https://www.ebi.ac.uk/chembl/explore/compound/CHEMBL63354/ ChEMBL].'''
**Optogenetics has been used to inhibit neurons ([https://scholar.googleusercontent.com/scholar.bib?q=info:E5ci0TmjTyUJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixuAMnI:ACTRDVEAAAAAas-GKnJgn-bjNlsNLChcKv4my2s&scisig=ACTRDVEAAAAAas-GKgEqKyhrCyTgoY7wITcfbIk&scisf=4&ct=citation&cd=-1&hl=en Boyden] [https://scholar.googleusercontent.com/scholar.bib?q=info:5bB4NZj9XJwJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixuAD4Q:ACTRDVEAAAAAas-GF4QQx1MktzR7KJjHy7lxqtc&scisig=ACTRDVEAAAAAas-GF0WwYhYzurZCN_BZ43PKYBA&scisf=4&ct=citation&cd=-1&hl=en Zhang]) and control motor responses in ''C. elegans'' ([https://scholar.googleusercontent.com/scholar.bib?q=info:DR_TtH156CwJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixuATj4:ACTRDVEAAAAAas-GVj4eXZwSNxuPraJTtvvWPi4&scisig=ACTRDVEAAAAAas-GVgi34VSVojs0nt7HO_YbU68&scisf=4&ct=citation&cd=-1&hl=en Nagel])
**Optogenetics has been used to inhibit neurons ([https://scholar.googleusercontent.com/scholar.bib?q=info:E5ci0TmjTyUJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixuAMnI:ACTRDVEAAAAAas-GKnJgn-bjNlsNLChcKv4my2s&scisig=ACTRDVEAAAAAas-GKgEqKyhrCyTgoY7wITcfbIk&scisf=4&ct=citation&cd=-1&hl=en Boyden] [https://scholar.googleusercontent.com/scholar.bib?q=info:5bB4NZj9XJwJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixuAD4Q:ACTRDVEAAAAAas-GF4QQx1MktzR7KJjHy7lxqtc&scisig=ACTRDVEAAAAAas-GF0WwYhYzurZCN_BZ43PKYBA&scisf=4&ct=citation&cd=-1&hl=en Zhang]) and control motor responses in ''C. elegans'' ([https://scholar.googleusercontent.com/scholar.bib?q=info:DR_TtH156CwJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixuATj4:ACTRDVEAAAAAas-GVj4eXZwSNxuPraJTtvvWPi4&scisig=ACTRDVEAAAAAas-GVgi34VSVojs0nt7HO_YbU68&scisf=4&ct=citation&cd=-1&hl=en Nagel])
**The effect of anion-conducting channelrhodopsins (ACRs) on the activity of the neuron is comparable to GABA<sub>A</sub> receptors.
**The effect of anion-conducting channelrhodopsins (ACRs) on the activity of the neuron is comparable to GABA<sub>A</sub> receptors.
**Optogenetics can control the activity of a genetically defined set of neurons to see if they are important for your topic of interest. e.g. express anion-conducting channelrhodopsins (ACRs, an inhibitory type of ChR) in α1β2γ2 GABA-R expressing neurons.
***Could we use optogenetics to clarify whether certain non-canonical propofol target receptors (e.g. α4β2 nAChR, HCN1) are necessary or sufficient for its effects?
***Assuming that α1β2γ2 GABA<sub>A</sub>R is the critical receptor, can we demonstrate which circuits play a critical role? As a starting point (from Brown's Part I):
## Excitatory cortical pyramidal neurons
## Galan-/GABA-ergic hypothalamic POA projections to monoaminergic brainstem nuclei: LC (NE), DR (5HT), vPAG (DA), TMN (His)
## GABAergic neurons in the TRN (thalamic reticular nucleus)
**'''Is the receptor, its components, or homologues of the gene expressed in different model organisms? What is the sequence similarity with human?'''
**'''Is the receptor, its components, or homologues of the gene expressed in different model organisms? What is the sequence similarity with human?'''
**'''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's lab specializes in light-sheet imaging and they have single neuron resolution where they can look at calcium currents (neuronal activity) in real time.
* ''C. elegans'' don't have any histamine signaling natively. You can make animals that express histamine-gated chloride channels to chemogenetically inactivate channel expressing neurons when histamine is given exogenously. '''Look for a GABA<sub>A</sub>R His-Cl worm line.
** He is going to send me some links to worm genetic databases, and some protocols for breeding and behavior.
===Phylogenetic Approach===
===Phylogenetic Approach===
*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.
*'''Next call 10/29.'''
*I am going to '''read up on propofol mechanisms in worms, and gap junctions''' before our next meeting on 10/29.
==DECODE==
*SEEG-electrodes allow us to collect LFP along the whole lead, individual neuron firing at the tips.
==CLAN==
==CLAN==
===Alpha entrainment analgesia study===
===Alpha entrainment analgesia study===
*How to leverage Ripple hardware/BATMAN (lab-grade, non-FDA approved device) to entrain or modulate alpha band?
**Successfully entrain alpha. What were we doing wrong? '''Is there anything in the literature that can guide a protocol modification?'''
**Successfully entrain alpha. What were we doing wrong? '''Is there anything in the literature that can guide a protocol modification?'''
**Can I incorporate withdrawal thresholds?
**Can I incorporate withdrawal thresholds?
*Caffeine = 138
*Caffeine = 138
==SCD PV==
* Talk to a circulators/scrubs with a lot of experience.
** Do we only have one model? Mostly
** How long have we had that one model? What did we use before that?
** Do the RNs track anywhere that the boots have been applied and to which legs?
** Where in the flowsheets is last liquid intake listed?
* BATMAN can capture data from the Philips monitor at 500 Hz.
* Can we get BATMAN to timestamp when the SCDs go off?
==CO2==
==CO2==
==Depression==
==Depression==
*Do ketamine, TIVA w/ propofol, TIVA w/ remimazolam, psychedelics, or burst suppression modulate the post-operative risk of depression?
*Do ketamine, TIVA w/ propofol, TIVA w/ remimazolam, psychedelics, or burst suppression modulate the post-operative risk of depression?
*OB vs. general surgery population, decreasing incidence of postpartum/post-op depression w/ single dose of ketamine.
==Young Blood==
==Young Blood==