Trace eyeblink conditioning requires the hippocampus but not autophosphorylation of αCaMKII in mice

Little is known about signaling mechanisms underlying temporal associative learning. Here, we show that mice with a targeted point mutation that prevents autophosphorylation of αCaMKII (αCaMKII^T286A) learn trace eyeblink conditioning normally. This forms a sharp contrast to the severely impaired spatial learning in the water maze and contextual fear conditioning observed in αCaMKII^T286A mutants. Importantly, hippocampal lesions impaired trace eyeblink conditioning in αCaMKII^T286A mice, suggesting a potential role of hippocampal αCaMKII-independent mechanisms. These results indicate that hippocampal signaling mechanisms that underlie temporal associative learning as assessed by trace eyeblink conditioning may differ from those of spatial and contextual learning.