| The brains of hibernating mammals undergo dramatic changes in temperature and activity during torpor. Previous work has shown that this extreme physiological state is correlated with changes in neural structure. This dissertation focuses on the characterization of these little-understood structural changes: Is torpor-related plasticity occurring globally throughout the brain? What is the time-course of neural plasticity throughout the torpor bout? Is the extent of plasticity dependent upon temperature? Is protein degradation the primary mechanism for structural and synaptic loss?;To investigate these questions, neurons were visualized using Lucifer Yellow injections, synaptic protein composition was determined using immunohistochemistry, and protein concentration was measured using quantitative Western blotting. The results show that neuronal dendrites and spines retract, and cell bodies contract when ground squirrels enter torpor. These structures change little over the course of several days, and then recover during the 2-hour return to euthermia. Similar structural changes take place in cortical, thalamic, and hippocampal cells, suggesting a global phenomenon. Animals hibernating at lower temperatures exhibit greater structural reduction. However, greater reduction is followed by greater regrowth during arousal, so that neural structure reaches the same final parameters. Changes in synaptic protein immunoreactivity are consistent with changes in microstructure, and also indicate substantial synaptic loss during torpor. Last, there is no net breakdown of protein during torpor entry, indicating that hibernators use a novel mechanism of protein dissociation and remobilization to effect large-scale changes.;This dissertation demonstrates large-scale and seemingly ubiquitous neural plasticity in a hibernator. This model of neural plasticity can be manipulated by altering ambient temperature, resulting in a predictable extent of structural and synaptic loss that is large in rate and magnitude. This loss appears to result from dissociation of proteins from the cytoskeleton and from synapses during entry into torpor. These dissociated proteins may serve as a reservoir for rapid and energetically-efficient rebuilding of synapses during the short return to euthermia. These results have improved our understanding of the extreme neural plasticity in the hibernator and have advanced the potential use of this model system for learning about processes including learning and memory, sleep, hypothermia, and neurodegeneration. |
