Adaptive responses to cellular stress in neurons of the hippocampus



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Disruptions of endoplasmic reticulum (ER) Ca²⁺ homeostasis are heavily linked to neuronal pathology. Depletion of ER Ca²⁺ stores can result in cellular dysfunction and potentially cell death, although adaptive processes exist to aid in survival. This dissertation examines the age and region-dependence of one postulated adaptive response to ER store depletion, store depletion (SD) HCN channel plasticity, in neurons of the dorsal (DHC) and ventral (VHC) hippocampus from adolescent and adult rats. Using whole-cell patch clamp recordings from the soma and dendrites of CA1 pyramidal neurons, the change in h-sensitive measurements in response to store depletion, induced by treatment with cyclopiazonic acid (CPA), a sarco/endoplasmic reticulum Ca²⁺-ATPase blocker were observed. While DHC and VHC neurons in adolescent animals responded to store depletion with a peri-somatic expression of SD h plasticity, it was found that adult animals express SD h plasticity with a dendritic and somato-dendritic locus of plasticity in DHC and VHC neurons, respectively. Furthermore, SD h plasticity in adults was dependent on membrane voltage and on the activation of L-type voltage gated Ca²⁺ channels. These results suggest that cellular responses to the impairment of ER function, or ER stress, are dependent upon brain region and age, and that the differential expression of SD h plasticity could provide a neural basis for region and age-dependent disease vulnerabilities.