Synaptic Failure in Postoperative Cognitive Dysfunction

The means to control the switch from spine to dendritic shaft synapses

How can preservation of excitation-transcription coupling prevent POCD ?

Postoperative cognitive dysfunction (POCD) is a serious health issue. A vast body of literature exists in the clinical aspects of this condition. In stark contrast, little amyloid load in conjunction with the bodily stress response following surgery and activation of CRF-expressing projection neurons from the hypothalamus destabilize spines - mainly in the hippocampus - probably by severing the F-actin cytoskeleton and depletion of the synaptic scaffold. Spines tend to collapse and we will follow up on the provocative hypothesis that spines become largely shaft synapses that might recover later on. Signaling mechanism will be addressed and circuit specific aspects included. The fill garment of advanced imaging, genetic, biochemical and electrophysiological tools will be employed to break ground. Most important, we anticupate that the signaling mechnisms under investigation will be druggable.