Investigation of age-related cognitive decline using mice as a model system: Neurophysiological correlates

Geoffrey G. Murphy, Vaibhavi Shah, Johannes W Hell, Alcino J. Silva

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Objective: Learning and memory impairments without overt pathology often accompany advancing age. To gain a better understanding of the underlying neuronal substrates associated with this age-related cognitive decline, the authors have begun to use mice as an animal model system. As described in the companion paper, mice exhibit age-related impairments in cognition. Here, the authors explore the possibility that age-related changes in neuronal function may be the result of deregulation of cytosolic free calcium homeostasis. Methods: Calcium homeostasis in young and aged mice was examined by measuring the slow after hyperpolarization (sAHP) in hippocampal neurons as well as assessing voltage-dependent calcium channel mediated long-term potentiation (vdccLTP). In addition, putative changes in phosphorylation of the L-type channel Cav1.2 by cAMP-dependent protein kinase were examined. Results: Both neurophysiological measures of calcium homeostasis indicated an increase in activity-dependent calcium influx. This increase was not the result of an age-related increase in phosphorylation of the L-type channel Ca v1.2 by cAMP-dependent protein kinase. Conclusions: Like in other areas of biomedical research, mice have become an invaluable research tool in the investigation of learning and memory. It is expected that similar benefits can be realized by developing mouse models for age-related cognitive decline.

Original languageEnglish (US)
Pages (from-to)1012-1021
Number of pages10
JournalAmerican Journal of Geriatric Psychiatry
Issue number12
StatePublished - Dec 2006
Externally publishedYes


  • Aging
  • Calcium
  • Learning and memory
  • Mice
  • Synaptic plasticity

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology


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