Investigation of age-related cognitive decline using mice as a model system: neurophysiological correlates.
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 afterhyperpolarization (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 Ca(V)1.2 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(V)1.2 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.
Murphy
Geoffrey G
GG
Department of Neurobiology, Brain Research Institute, University of California, Los Angeles, Los Angeles, CA 90095-1761, USA.
Shah
Vaibhavi
V
Hell
Johannes W
JW
Silva
Alcino J
AJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000375:Aging / Q000523:psychology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D003072:Cognition Disorders / Q000503:physiopathology*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006706:Homeostasis; D051379:Mice; D008960:Models, Psychological; D009482:Neurophysiology / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
D020746:Calcium Channels, L-Type; D018691:Excitatory Amino Acid Antagonists; D015763:2-Amino-5-phosphonovalerate; D002118:Calcium