Circadian modulation of learning and memory in fear-conditioned mice.

Endogenous processes referred to as circadian oscillators generate many of the daily rhythms in physiology and behavior of a variety of animals including humans. We investigated the possible circadian regulation of acquisition, recall and extinction in two strains of mice (C-57/6J and C-3H). Mice were trained in either the day or night with a tone and context fear conditioning protocol. The mice were then tested over the course of several days for their ability to recall the training. When comparing the performance of animals in the day and night, the mice acquired the conditioning faster in the day than in the night. Furthermore, the recall for context and tone consistently peaked during the day for at least 3 days after training, irrespective of the time of training. Finally, the loss of this training (or extinction) exhibited a rhythm in that mice trained in night exhibited a greater degree of extinction than mice trained in the day. For all of these rhythms in acquisition, recall, and extinction the phase of the rhythm was controlled by the prior light-dark (LD) cycle. When we reversed the phase of the LD cycle, the phase of the rhythm also reversed. Importantly, all three of the rhythms also continued in constant darkness demonstrating the endogenous, and presumably circadian nature, of the rhythms.