Analysis of the performance-enhancing effects of hippocampal lesions in rat serial reaction time task

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Sequential learning is a basic form of knowledge acquisition, namely implicit or procedural learning, which is tested in humans and primates using serial reaction time tasks. In Parkinson patients and by use of brain imaging techniques, it could be shown that fronto-striatal and dopaminergic processed play a central role in sequential behavior. We have developped a rat version with high face validity of the serial reaction time task to study neural mechanisms including manipulative approaches, and our translational studies to validate the test showed that dopamine lesions can impair sequential behavior, especially during learning. More recently, we studied the hippocampus, which is thought to play a role for explicit and spatial learning and memory. Surprisingly, we repeatedly found that lesions of the hippocampus substantially enhanced performance in our task, which supports the hypothesis that simultaneous information provided by basal ganglia and hippocampus to frontal cortical sites can compete with each other during sequential learning and that hippocampal information may not play a crucial role during sequential learning. Here, we want to address some yet unresolved questions regarding this lesion effect: a) Is the performance-enhancing effect specific for sequential learning or does it improve instrumental learning which is required in our task, b) are lesions of the intermediate hippocampus, which provided important inputs to frontal cortical sites, sufficient for the effect?, and c) are the effects specific for task acquisition and can they also be induced by reversible pharmacological blockade of the hippocampus?