Is It Memory or Is It Death? Caspase-3 and Memory Formation

"Caspase-3 is a protease associated with development, cancer defense, and various disease states including Stroke, Alzheimer's and Parkinson's. Activation of caspase-3 is normally thought of as the terminal step in the biochemical cascade of apoptosis (programmed cell death). However, it is present in healthy adult neurons. Is it being expressed, potentially for decades, by these healthy cells in preparation for a response to noxious stimuli? Or does it have a role in the homeostatic regulations of healthy cells? I have undertaken an investigation of a possible role for caspase-3 in neurons unrelated to an apoptotic fate. Here I will show novel data that a natural learning experience---hearing the sound of birdsong---triggers a brief increase in active caspase-3 in the auditory forebrain of adult male zebra finches that does not lead to cell death. Active caspase-3 is detected within 2 min of stimulation, peaks at 10 min, and is gone by 20 min. Imaging shows this activation to be localized to the post-synaptic dendritic spine. Localized infusion of a caspase-3 inhibitor during initial song exposure blocks formation of a memory of that song (as assessed using the habituation of the ZENK IEG response as an indicator of memory). I also have investigated the regulation (turning on and off) of caspase-3 in the neuron by the protein xIAP (x-linked inhibitor of apoptosis protein). Thus caspase-3, apparently, has an essential role in memory formation. A role that utilizes caspase-3 in a novel way, as it does not lead to cell death. From these data and evidence drawn from published reports, I develop a new model for memory trace capture, the ""Base Relief Model"" of losing synapses to gain memory."

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Neuroscience

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Huesmann, Graham Rowell

Contributors dc:contributor

• Clayton, David F.

• Biology, Neuroscience

Language dc:language

eng

Identifier

(MiAaPQ)AAI3182282

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/82502