Altered Calcium Metabolism in Aging CA1 Hippocampal Pyramidal Neurons

• Published in: The Journal of neuroscience Vol. 33; no. 18; pp. 7905 - 7911
• Main Authors: Oh, M. Matthew, Oliveira, Fernando A., Waters, Jack, Disterhoft, John F.
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 01.05.2013
• Subjects: Age Factors; Aging - physiology; Analysis of Variance; Animals; Biophysics; CA1 Region, Hippocampal - cytology; Calcium - metabolism; Chelating Agents - pharmacokinetics; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacokinetics; Electric Stimulation; Fluorescent Dyes - metabolism; In Vitro Techniques; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Microscopy, Confocal; Patch-Clamp Techniques; Pyramidal Cells - drug effects; Pyramidal Cells - physiology; Rats; Rats, Inbred F344; Time Factors
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/JNEUROSCI.5457-12.2013

Altered neuronal calcium homeostasis is widely hypothesized to underlie cognitive deficits in normal aging subjects, but the mechanisms that underlie this change are unknown, possibly due to a paucity of direct measurements from aging neurons. Using CCD and two-photon calcium imaging techniques on CA1 pyramidal neurons from young and aged rats, we show that calcium influx across the plasma membrane increases with aging, and that this change is countered by increased intracellular calcium buffering. The additional buffer in aging neurons balances the increased calcium influx following a small number (<3) action potentials, but is overwhelmed during sustained or theta-like activity which leads to a greater rise in intracellular calcium concentration in aging than that in young neurons. Our results demonstrate that calcium overload occurs regularly in aging CA1 pyramidal neurons under physiological conditions. This overload may be a critical factor in age-related decline in hippocampus-dependent cognitive function.