Enhancement of encoding and retrieval functions through theta phase-specific manipulation of hippocampus

Assessing the behavioral relevance of the hippocampal theta rhythm has proven difficult, due to a shortage of experiments that selectively manipulate phase-specific information processing. Using closed-loop stimulation, we triggered inhibition of dorsal CA1 at specific phases of the endogenous theta rhythm in freely behaving mice. This intervention enhanced performance on a spatial navigation task that requires the encoding and retrieval of information related to reward location on every trial. In agreement with prior models of hippocampal function, the behavioral effects depended on both the phase of theta and the task segment at which we stimulated. Stimulation in the encoding segment enhanced performance when inhibition was triggered by the peak of theta. Conversely, stimulation in the retrieval segment enhanced performance when inhibition was triggered by the trough of theta. These results suggest that processes related to the encoding and retrieval of task-relevant information are preferentially active at distinct phases of theta.