Nucleus Reuniens: Circuitry, Function, and Dysfunction

The nucleus reuniens (RE) of the ventral midline thalamus is intimately connected with forebrain structures involved in higher-order functions and thus serves a critical role in those functions – both affective and cognitive behaviors. RE is strongly reciprocally linked with the hippocampus (HF) and medial prefrontal cortex (mPFC) and hence is pivotally positioned to affect these two structures – as well as their interactions. The HF distributes densely to the mPFC, but there are no return mPFC-HF projections; accordingly, RE is the main route of communication from the mPFC to the HF. Alterations of RE have been shown to disrupt various functions including working memory/spatial working memory (SWM), “executive functions,” and affective behaviors. Specifically, the inactivation of RE alters: (1) synchronous oscillations between the HF and mPFC and performance on SWM tasks; (2) executive functions such as attention, goal-directed behavior, and behavioral flexibility, mainly dependent on RE projections to the mPFC and orbital cortices; and (3) affective behavior, primarily fear and fear extinction, which have been associated with a RE-mediated disruption of mPFC actions on the hippocampus. RE cells in anesthetized and behaving animals exhibit a range of discharge characteristics consistent with the functional properties of RE. For instance, subpopulations of RE neurons (1) fire at significantly higher rates in active waking than in sleep with subsets discharging synchronously with the hippocampal theta rhythm; (2) display spatial properties – place cells, head direction cells, and border cells; and (3) exhibit “trajectory-dependent” activity; that is, RE discharge “predicts” directional choices (or intended movements) to thereby convey action plans from the mPFC to the HF for goal-directed behavior. Further, RE lesions significantly disrupt the stability of hippocampal place cells. Finally, alterations of RE have been linked to the CNS disorders, schizophrenia (SZ), and epilepsy. Regarding SZ, the disruption of RE produces abnormal HF-mPFC oscillations leading to an excessive release of dopamine and SZ-like effects including lapses of memory and cognition. Regarding epilepsy, RE is reportedly a primary conduit in the spread of HF-initiated seizure activity to other cortical regions in temporal lobe epilepsy. In summary, nucleus reuniens serves a critical role in mnemonic, executive, and affective functions, and alterations of RE would disrupt these functions possibly leading to CNS disorders.