title: Model of anaesthetic induction by unilateral intracerebral microinjection of GABAergic agonists.
abstract: General anaesthetic agents induce loss of consciousness coupled with suppression of movement, analgesia and amnesia. Although these diverse functions are mediated by neural structures located in wide-ranging parts of the neuraxis, anaesthesia can be induced rapidly and reversibly by bilateral microinjection of minute quantities of γ-aminobutyric acid (GABA)A -R agonists at a small, focal locus in the mesopontine tegmentum (MPTA). State switching under these circumstances is presumably executed by dedicated neural pathways and does not require widespread distribution of the anaesthetic agent itself, the classical assumption regarding anaesthetic induction. Here it was asked whether these pathways serve each hemisphere independently, or whether there is bilateral redundancy such that the MPTA on each side is capable of anaesthetizing the entire brain. Either of two GABAA -R ligands were microinjected unilaterally into the MPTA in awake rats, the barbiturate modulator pentobarbital and the direct receptor agonist muscimol. Both agents, microinjected on either side, induced clinical anaesthesia, including bilateral atonia, bilateral analgesia and bilateral changes in cortical activity. The latter was monitored using c-fos expression and electroencephalography. This action, however, was not simply a consequence of suppressing spike activity in MPTA neurons, as unilateral (or bilateral) microinjection of the local anaesthetic lidocaine at the same locus failed to induce anaesthesia. A model of the state-switching circuitry that accounts for the bilateral action of unilateral microinjection and also for the observation that inactivation with lidocaine is not equivalent to inhibition with GABAA -R agonists was proposed. This is a step in defining the overall switching circuitry that underlies anaesthesia.
authors.affiliation: Department of Cell and Developmental Biology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
authors.forename: Marshall
authors.identifier: http://orcid.org/0000-0001-8206-3301
authors.initials: M
authors.lastname: Devor
authors.affiliation: Department of Cell and Developmental Biology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zalkind
authors.affiliation: Department of Cell and Developmental Biology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Fishman
authors.affiliation: Department of Cell and Developmental Biology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
authors.forename: Anne
authors.initials: A
authors.lastname: Minert
mesh_terms: D000768:Anesthesia, General / Q000379:methods*; D018681:Anesthetics, General / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D065821:Pontine Tegmentum / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018681:Anesthetics, General; D018755:GABA Agonists
keywords: GABAA-R agonist; MPTA; anaesthesia; brainstem; general anaesthesia