The human hippocampus plays a crucial role in episodic memory; the who, what, where memories that define our lives. In the rodent, well-defined anatomy and physiology make the structure an ideal model system; amenable to circuit manipulations and observations designed to test hypotheses concerning how memories are formed and used. Here I will present our recent work in mice which combines anatomical characterization, genetic interventions and in vivo recording to address how noncononical inputs and outputs influence information flow in the hippocampus. I will first introduce our study identifying a novelty signaling hub in the hypothalamus – the supramammillary nucleus (SuM). Unique about this region is that it not only responds broadly to novel stimuli, but segregates and selectively routes different types of information to discrete cortical targets, the dentate gyrus (DG) and CA2 fields of the hippocampus, for the modulation of mnemonic processing. Next, I will describe ongoing work focused on how CA2’s output impacts both local and distal circuits, including our identification and characterization of a novel descending glutamatergic projection from CA2 pyramidal cells to PV+ neurons in the MS that can regulate cholinergic tone and hippocampal memory. Zoom link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421