Disterhoft J F, Thompson L T, Moyer J R, Mogul D J
Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA.
Life Sci. 1996;59(5-6):413-20. doi: 10.1016/0024-3205(96)00320-7.
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.
海马体依赖的痕迹性眨眼条件反射已被证明会受到衰老的影响。衰老的动物需要更多的试验来建立联系，并且更有可能无法学会这项任务。海马体神经元在条件反射后，爆发后超极化（AHPs）减少，适应性降低，呈现出时间依赖性，这可能与海马体在学习巩固中的作用有关。衰老兔子的CA1神经元表现出AHPs增加和更多的适应性，即它们的兴奋性较低，钙动作电位较大。这些与年龄相关的变化可能是衰老兔子学习缺陷的基础。亲脂性钙通道阻滞剂尼莫地平在低浓度时可降低衰老但非年轻CA1神经元的AHPs、适应性和钙动作电位。尼莫地平还能提高衰老但非年轻动物和人类在包括眨眼条件反射在内的各种任务中的学习速度。衰老哺乳动物神经元中钙处理的改变是一个显著变化，可通过药物进行调控，并且可能是衰老过程中学习和认知能力改变的一个重要因素。
