Trace eyeblink conditioning in rabbits demonstrates heterogeneity of learning ability both between and within age...

Rabbits 2 to 41 months of age were conditioned in the 500 ms trace eyeblink paradigm to cross-sectionally define the age of onset and the severity of age-associated impairments in acquisition of this relatively difficult hippocampally dependent task. Using a strict behavioral criterion of 80% conditioned responses (CRs), age-associated learning impairments were significant by 24 months of age. Among rabbits that successfully reached this criterion, impairments in acquisition plateaued at 30 months of age. However, the proportion of severely impaired rabbits (that failed to reach the 80% criterion) continued to increase age dependently. Using an easier criterion of 8 out of 10 CRs, behavioral impairments were not detected until 30 months of age, and cases of severe impairment (failure to reach criterion) were rare. Additional controls demonstrated that the deficits observed were not attributable to nonassociative changes that might have artifactually skewed the data. Even severely impaired 36-month-old rabbits were able to reach a criterion of 80% CRs when switched from a trace to a delay conditioning task that is not hippocampally dependent. The results are discussed in terms of operationally defining and predicting behavioral effects of aging, hypothetical neural mechanisms, and efficient experimental design.