Anesthetic loss of consciousness induced by chemogenetic excitation of mesopontine effector neurons.

Mark Baron, Kristina Vaso, Tamir Avigdor, Yelena Charit, Anne Minert, Marshall Devor

Research output: Contribution to journalArticlepeer-review

Abstract

Although general anesthesia is normally induced by systemic dosing, an anesthetic state can be induced in rodents by microinjecting minute quantities of GABAergic agents into the brainstem mesopontine tegmental anesthesia area (MPTA). Correspondingly, lesions to the MPTA render rats relatively insensitive to standard anesthetic doses delivered systemically. Using a chemogenetic approach we have identified and characterized a small subpopulation of neurons restricted to the MPTA which, when excited, render the animal anesthetic by sensorimotor (immobility) and electroencephalographic (EEG) criteria. These “effector-neurons” do not express GABAAδ-Rs, the likely target of GABAergic anesthetics. Rather, we report a distinct sub-population of nearby MPTA neurons which do. During anesthetic induction these likely excite the effector-neurons by disinhibition. Within the effector population ~ 70% appear to be glutamatergic, ~30% GABAergic and ~ 40% glycinergic. Most are projection neurons that send ascending or descending axons to distant targets associated with the individual functional components of general anesthesia: atonia, analgesia, amnesia, and loss-of-consciousness.

Original languageAmerican English
Article number114169
Number of pages15
JournalExperimental Neurology
Volume357
DOIs
StatePublished - Nov 2022

Keywords

  • Anesthesia
  • Chemogenetics
  • Loss-of-consciousness
  • MPTA
  • Mesopontine tegmentum

All Science Journal Classification (ASJC) codes

  • Neurology
  • Developmental Neuroscience

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