Evidence of Selective Learning Deficits on Tests of Pavlovian and Instrumental Conditioning in α-CaMKIIT286A Mutant Mice

Abstract

Mice carrying a threonine286 to alanine mutation in subunit α of Ca2+/CaM-dependent protein kinase II (α-CaMKIIT286A) have been reported to show deficits in hippocampal long-term potentiation as well as spatial learning deficits similar to those induced in mice with hippocampal lesions. In this series, we sought to extend this analysis by investigating the performance of α-CaMKII mutants on other, potentially hippocampal, learning tasks. Experiment 1 examined fear conditioning, Experiment 2 examined the acquisition of free-operant instrumental conditioning and its dependence upon the action-outcome association, and Experiment 3 assessed interval timing using an instrument version of the peak procedure.We found evidence of a deficit in contextual fear conditioning in Experiment 1 and in peak timing in Experiment 3, but neither a deficit in fear conditioning to a discrete tone CS nor in the acquisition of instrumental conditioning in Experiment 2. Furthermore, all of the mice in Experiment 2 showed a normal instrumental outcome devaluation effect, suggesting that encoding of the action-outcome association was unaffected by this point mutation. It appears, therefore, that although learning in CaMKII mutants is affected on specific tasks, they do not have a general learning deficit, and that the influence of this mutation, and therefore, of α-CaMKII, is both localized anatomically and relatively specialized functionally.