Effect of circadian phase on context and cued fear conditioning in C57BL/6J mice

We examined context-dependent and tone-cued fear conditioning during the activity and rest periods of C57BL/6J mice. Wheel-running activity was measured continuously as a marker of circadian phase. To control the effects of light on the response, the animals were kept in a skeleton photoperiod (two 15-min light pulses per day, indicating the beginning and the end of the day). Half the animals were trained and tested for context-dependent fear conditioning 2 h after the morning light pulse; the other half were trained and tested 2 h after the evening light pulse. Animals were tested every 24 h for 5 days to analyze the conditioned response and the rate of extinction. They were then trained for tone-cued fear conditioning at the same time and tested for 5 consecutive days. A significant difference between the morning and the evening groups was observed in the conditioning level and extinction rate of context-dependent fear conditioning, but not in tone-cued fear conditioning. These results suggest a modulating effect of the biological clock on the context fear-conditioning pathway.