Interactions between the Lateral Habenula and the Hippocampus: Implication for Spatial Memory Processes

The lateral habenula (LHb) is an epithalamic structure connected with both the basal ganglia and the limbic system and that exerts a major influence on midbrain monoaminergic nuclei. The current view is that LHb receives and processes cortical information in order to select proper strategies in a variety of behavior. Recent evidence indicates that LHb might also be implicated in hippocampus-dependent memory processes. However, if and how LHb functionally interacts with the dorsal hippocampus (dHPC) is still unknown. We therefore performed simultaneous recordings within LHb and dHPC in both anesthetized and freely moving rats. We first showed that a subset of LHb cells were phase-locked to hippocampal theta oscillations. Furthermore, LHb generated spontaneous theta oscillatory activity, which was highly coherent with hippocampal theta oscillations. Using reversible LHb inactivation, we found that LHb might regulate dHPC theta oscillations. In addition, we showed that LHb silencing altered performance in a hippocampus-dependent spatial recognition task. Finally, increased coherence between LHb and dHPC was positively correlated to the memory performance in this test. Collectively, these results suggest that LHb functionally interacts with the hippocampus and is involved in hippocampus-dependent spatial information processing.