We examined context-dependent and tone-cued fear conditioning during the ac
tivity and rest periods of C57BL/6J mice. Wheel-running activity was measur
ed continuously as a marker of circadian phase. To control the effects of l
ight 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 da
y). Half the animals were trained and tested for context-dependent fear con
ditioning 2 h after the morning light pulse; the other half were trained an
d 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 mornin
g and the evening groups was observed in the conditioning level and extinct
ion rate of context-dependent fear conditioning, but not in tone-cued fear
conditioning. These results suggest a modulating effect of the biological c
lock on the context fear-conditioning pathway.