Sustained increase in alpha 5GABA sub( A) receptor function impairs memory after anesthesia

Many patients who undergo general anesthesia and surgery experience cognitive dysfunction, particularly memory deficits that can persist for days to months. The mechanisms underlying this postoperative cognitive dysfunction in the adult brain remain poorly understood. Depression of brain function during anesthesia is attributed primarily to increased activity of y-aminobutyric acid type A receptors (GABA sub( A)R), and it is assumed that once the anesthetic drug is eliminated, the activity of GABA sub( A)Rs rapidly returns to baseline and these receptors no longer impair memory. In this article, using a murine model, the researchers found that a single in vivo treatment with the injectable anesthetic etomidate increased a tonic inhibitory current generated by alpha 5 subunit-containing GABA sub( A)Rs ( alpha 5GABA sub( A)Rs) and cell-surface expression of alpha 5GABA sub( A)Rs for at least 1 week. The sustained increase in alpha 5GABA sub( A)R activity impaired memory performance and synaptic plasticity in the hippocampus. Inhibition of alpha 5GABA sub( A)Rs completely reversed the memory deficits after anesthesia.