Eur J Neurosci. 2016 Jan 25. doi: 10.1111/ejn.13186. [Epub ahead of print]

Model of anesthetic induction by unilateral intracerebral microinjection of GABAergic agonists.

Devor M1, Zalkind V1, Fishman Y1, Minert A1.

• 1Department of Cell and Developmental Biology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.

Abstract

General anesthetic 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, anesthesia can be induced rapidly and reversibly by bilateral microinjection of minute quantities of GABAA -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 anesthetic agent itself, the classical assumption regarding anesthetic induction. Here we asked whether these pathways serve each hemisphere independently, or whether there is bilateral redundancy such that the MPTA on each side is capable of anesthetizing 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 anesthesia 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 anesthetic lidocaine at the same locus failed to induce anesthesia. We propose 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. This is a step in defining the overall switching circuitry that underlies anesthesia. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS:

MPTA ; GABAA-R agonist; anesthesia; brainstem; general anesthesia

PMID:

26804488