Year: 2015
Type: dissertation
Abstract: Many patients who undergo surgery and general anesthesia suffer from memory impairments for weeks to months afterwards. However, the mechanisms underlying this phenomenon remain poorly understood. We previously showed that postanesthetic memory deficits are associated with a sustained increase in tonic inhibitory conductance in hippocampal neurons. Interestingly, astrocytes offer a new target for studying this disorder due to their interconnectedness with GABAergic signaling and tonic inhibition. Specifically, astrocytes express GABAA receptors, the primary target of anesthetics, as well as secrete numerous soluble factors that regulate memory. This thesis explores the underpinnings of anesthetic-induced enhancement of tonic inhibition in hippocampal neurons with a cell culture model. The results show that activation of astrocytic GABAA receptors is necessary and sufficient to trigger an increase in tonic current, and that the interleukin-1 receptor and p38 MAP kinase subsequently participate in up-regulating GABAA receptor function in neurons. These results bring us closer to understanding, treating and preventing postanesthetic memory deficits.
Source: TSpace (University of Toronto)
Author: Sean Christopher Haffey
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2602644921