Diencephalic modulation of the hippocampus in affective and cognitive behavior

Very few diencephalic structures project directly to the hippocampus. Two diencephalic nuclei, however, with pronounced direct projections to the hippocampus, are the nucleus reuniens (RE) of the midline thalamus and the supramammillary nucleus (SuM) of the caudal hypothalamus. As reviewed herein, RE and SuM distribute to separate sites in the hippocampus and accordingly largely exert distinct effects on the hippocampus. Specifically, RE is a major interface between the hippocampus and the medial prefrontal cortex (mPFC) and thus mainly serves functions associated with the hippocampal formation and the mPFC, namely, working memory, executive functions, and affective behaviors, primarily fear. By comparison, the SUM projects prominently to the dentate gyrus (DG) of the hippocampus, the major recipient zone of afferents from the entorhinal cortex (EC), and accordingly the SuM serves to enhance the activity of DG cells rendering them more responsive to inputs from the EC. This serves to promote the transfer, encoding, and storage of information from the EC to the DG — supporting learning and memory processes of the hippocampus. In sum, the RE and SuM exert a powerful influence on the hippocampus in the modulation/control of numerous affective, cognitive, and mnemonic functions.