Numerous studies have found altered Ca²⁺ homeostasis in neurons during the ageing process. However, it remains unclear whether there is one primary initiating dysfunction or whether multiple alterations develop in parallel. Previously, we found that the density of available L-type Ca²⁺ channels increases in rat hippocampal neurons during ageing (Thibault & Landfield, 1996). Recently, we found that during repetitive (7 Hz) synaptic stimulation in hippocampal slices, [Ca²⁺] rises more in neurons from aged than from young adult rats. However, this difference becomes apparent only after several seconds of stimulation above spike threshold. The elevated [Ca²⁺] is correlated with impaired short-term synaptic frequency facilitation, a correlate of deficient memory. Facilitation was also impaired by exposure to Bay K 8644, an L-type channel agonist (Thibault et al. 2001). The delayed [Ca²⁺] elevation in aged neurons is potentially consistent with several possible mechanisms of Ca²⁺ dyshomeostasis, including greater influx, impaired sequestration or extrusion and/or impaired mitochondrial function. However, recent findings in a hippocampal culture model suggest that sustained Ca²⁺-induced Ca²⁺ release can be triggered by elevated Ca²⁺ influx (Clodfelter et al. 2002) and therefore, also could account in part for the delayed [Ca²⁺] elevation in aged neurons.

All procedures accord with current local guidelines.