Nonpharmacological amelioration of age-related learning deficits: The impact of hippocampal theta-triggered training

摘要

Age-related learning deficits are often attributed to deterioration of hippocampal function. Conversely, a well studied index of hippocampal activity, the theta rhythm, is known to enhance hippocampal plasticity and accelerate learning rate in young subjects, suggesting that manipulations of theta activity might be used as a means to counteract impairments related to the aging process. Here, young and older rabbits were given eyeblink conditioning trials either when exhibiting hippocampal theta (theta+) or regardless of hippocampal activity (yoked control). Although, as expected, older-yoked control animals showed a learning deficit, the older theta+ group learned as fast as young controls, demonstrating that aging deficits, at least in eyeblink classical conditioning, can be overcome by giving trials during episodes of hippocampal theta activity. The use of several learning criteria showed that the benefits of hippocampal theta occur in multiple phases of learning that may depend on different cognitive or motor processes. Whereas there was a benefit of theta-triggered training in both age groups during the early phase of acquisition, the enhancement persisted in older animals, peaking during later performance. These findings have implications for theories of age-related memory deficits and may contribute to the development of beneficial treatments.