Journal
NEUROBIOLOGY OF AGING
Volume 33, Issue 11, Pages 2715-2720Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2011.12.030
Keywords
Sodium channel; Excitability; Action potential threshold; Hippocampus
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Funding
- Pfizer
- Medical Research Council
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Cognitive decline occurs during normal aging and is likely to be reflected in the neurophysiological properties of neural circuits with key roles in cognition, for example those of the limbic system. To identify candidate neurophysiological changes we used patch clamp methods to compare the intrinsic excitability properties of hippocampal CA1 pyramidal neurons of mature adult (8-10 month) and aged (22-24 month) mice. Resting potential, input resistance, and the sag observed on injection of hyperpolarizing current were not age-dependent. In contrast, the patterns of spike firing observed with depolarizing current injections demonstrated the presence of an age-related hypoexcitability. Action potential waveform analysis revealed that spike thresholds were approximately 3 mV more depolarized in aged animals. In line with this, voltage clamp recordings of Na+ currents from nucleated macropatches exhibited an approximate 3 mV depolarizing shift in the voltage-dependence of activation gating. Inactivation curves, in contrast, were not different. These data indicate alterations in Na+ channel activation gating contribute to neuronal hypoexcitability in aging, and therefore may be a factor in age-related cognitive decline. (C) 2012 Elsevier Inc. All rights reserved.
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