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Calcium-dependent afterhyperpolarization and learning in young and aging hippocampus
J F Disterhoft1, L T Thompson, J R Moyer
1Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA.
Life Sciences
|January 1, 1996
Summary
Aging impairs hippocampal learning, evidenced by increased neuronal excitability and reduced learning rates. The calcium channel blocker nimodipine ameliorates these age-related neuronal changes and improves learning in aging mammals.
Area of Science:
- Neuroscience
- Aging Research
- Cognitive Science
Background:
- Aging negatively impacts hippocampus-dependent learning, requiring more trials for association acquisition.
- Hippocampal neurons in aging animals exhibit altered electrophysiological properties, including changes in afterhyperpolarizations (AHPs) and accommodation.
- These age-related neuronal alterations in the hippocampus may underlie cognitive deficits observed in aging.
Purpose of the Study:
- To investigate the effects of aging on hippocampal neuronal function and learning.
- To examine the potential of nimodipine, a calcium channel blocker, in mitigating age-related learning impairments.
- To explore the role of altered calcium handling in cognitive decline associated with aging.
Main Methods:
- Utilized trace eyeblink conditioning to assess learning in aging and young rabbits.
- Electrophysiological recordings were performed on CA1 hippocampal neurons to measure AHPs, accommodation, and calcium action potentials.
- Administered nimodipine to evaluate its effects on neuronal properties and learning rates in aging animals.
Main Results:
- Aging rabbits showed impaired trace eyeblink conditioning compared to young rabbits.
- Aging CA1 neurons exhibited increased AHPs, greater accommodation, and larger calcium action potentials, indicating reduced excitability.
- Nimodipine treatment in aging rabbits normalized AHP, accommodation, and calcium action potential properties and enhanced learning rates without affecting young animals.
Conclusions:
- Age-related changes in hippocampal CA1 neuronal excitability, particularly altered calcium handling, contribute to learning deficits.
- Pharmacological modulation with nimodipine can reverse these detrimental age-related neuronal changes and improve cognitive function.
- Targeting calcium channel function presents a potential therapeutic strategy for age-related cognitive decline.