Age-related impairment in the 250-millisecond delay eyeblink classical conditioning procedure in C57BL/6 mice.

In this study we tested 4-, 9-, 12-, and 18-month-old C57BL/6 mice in the 250-msec delay eyeblink classical conditioning procedure to study age-related changes in a form of associative learning. The short life expectancy of mice, complete knowledge about the mouse genome, and the availability of transgenic and knock-out mouse models of age-related impairments make the mouse an excellent species for expanding knowledge on the neurobiologically and behaviorally well-characterized eyeblink classical conditioning paradigm. Based on previous research with delay eyeblink conditioning in rabbits and humans, we predicted that mice would be impaired on this cerebellar-dependent associative learning task in middle-age, at ~9 months. To fully examine age differences in behavior in mice, we used a battery of additional behavioral measures with which to compare young and older mice. These behaviors included the acoustic startle response, prepulse inhibition, rotorod, and the Morris water maze. Mice began to show impairment in cerebellar-dependent tasks such as rotorod and eyeblink conditioning at 9 to 12 months of age. Performance in hippocampally dependent tasks was not impaired in any group, including 18-month-old mice. These results in mice support results in other species, indicating that cerebellar-dependent tasks show age-related deficits earlier in adulthood than do hippocampally dependent tasks.