α5GABA Receptors Mediate Tonic Inhibition in the Spinal Cord Dorsal Horn and Contribute to the Resolution Of Hyperalgesia.

Neuronal inhibition mediated by GABA receptors constrains nociceptive processing in the spinal cord, and loss of GABAergic inhibition can produce allodynia and hyperalgesia. Extrasynaptic α5 subunit-containing GABA receptors (α5GABA Rs) generate a tonic conductance that inhibits neuronal activity and constrains learning and memory; however, it is unclear whether α5GABA Rs similarly generate a tonic conductance in the spinal cord dorsal horn to constrain nociception. We assessed the distribution of α5GABA Rs in the spinal cord dorsal horn by immunohistochemical analysis, and the activity and function of α5GABA Rs in neurons of the superficial dorsal horn using electrophysiological and behavioral approaches in male, null-mutant mice lacking the GABA R α5 subunit (Gabra5-/-) and wild-type mice (WT).

Sustained increase in α5GABAA 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 γ-aminobutyric acid type A receptors (GABA(A)Rs), and it is assumed that once the anesthetic drug is eliminated, the activity of GABA(A)Rs rapidly returns to baseline and these receptors no longer impair memory.

Inhibition of α5 γ-Aminobutyric acid type A receptors restores recognition memory after general anesthesia.

Background: General anesthetics cause cognitive deficits that persist much longer than would be expected on the basis of their pharmacokinetics. The cellular mechanisms underlying these postanesthetic cognitive deficits remain unknown. γ-Aminobutyric acid type A (GABA(A)) receptors are principal targets for most anesthetics.