Regional knockdown of NDUFS4 implicates a thalamocortical circuit mediating anesthetic sensitivity.

ABSTRACT: Knockout of the mitochondrial complex I protein, NDUFS4, profoundly increases sensitivity of mice to volatile anesthetics. In mice carrying an Ndufs4lox/lox gene, adeno-associated virus expressing Cre recombinase was injected into regions of the brain postulated to affect sensitivity to volatile anesthetics. These injections generated otherwise phenotypically wild type mice with region-specific, postnatal inactivation of Ndufs4, minimizing developmental effects of gene loss. Sensitivities to the volatile anesthetics isoflurane and halothane were measured using loss of righting reflex (LORR) and movement in response to tail clamp (TC) as endpoints. Knockdown (KD) of Ndufs4 in the vestibular nucleus produced resistance to both anesthetics for movement in response to TC. Ndufs4 loss in the ce

SUBMITTER: Ramadasan-Nair R 

PROVIDER: S-EPMC5685608 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature