Calcium-dependent afterhyperpolarization and learning in young and aging hippocampus

Hippocampally-dependent trace eyeblink conditioning has been shown to be affected by aging. Aging animals take more trials to acquire the association and are more likely to be unable to learn the task. Hippocampal neurons show decreased post-burst afterhyperpolarizations (AHPs) and less accomodation after conditioning, in a time-dependent fashion which may relate to the role of hippocampus in learning consolidation. CA1 neurons in aging rabbits show increased AHPs and more accomodation, i.e., they are less excitable, and larger calcium action potentials. These age-related changes may underlie the learning deficits in aging rabbits. The lipophylic calcium channel blocker nimodipine reduces the AHP, accomodation and calcium action potential at low concentrations in aging but not young CA1 neurons. Nimodipine also enhances learning rate in a variety of tasks, including eyeblink conditioning, in aging but not young animals and humans. Altered calcium handling by neurons of aging mammals is a striking change, is pharmacologically manipulable, and may be an important factor in altered learning and cognitive abilities in the aging.