The ability to recognize information incongruous with previous experience is critical for survival, thus novelty signals in the mammalian brain have evolved to enhance attention, perception and memory 1-3 . Although the importance of regions such as the ventral tegmental area 4-6 and locus coeruleus 6,7 in broadly signaling novelty has been well established, these diffuse monoaminergic transmitters have yet to be shown to convey specific information regarding the type of stimuli that drive them 6 . Whether distinct types of novelty, such as contextual and social novelty, are differently processed and routed in the brain remain unclear. Here we identify a novelty hub in the hypothalamus -the supramammillary nucleus (SuM) 8 . 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. Taking advantage of a novel SuM-Cre transgenic mouse, we found that DG-projecting SuM neurons are activated by contextual novelty while the SuM-CA2 circuit is preferentially activated by novel social encounters. Circuitbased manipulation demonstrated that divergent novelty channeling in these projections significantly modifies hippocampal-based contextual or social memory. This content-

Highlights d CA2 silencing results in increased excitability of the recurrent CA3 network d A loss of CA2 transmission leads to unexpected network pathophysiology d Spatially triggered network hyperexcitability events mimic single place fields d CA2 driven feedforward inhibition in CA3 is crucial for hippocampal E/I balance

Contextual learning involves associating cues with an environment and relating them to past experience. Previous data indicate functional specialization within the hippocampal circuit: the dentate gyrus (DG) is crucial for discriminating similar contexts, whereas CA3 is required for associative encoding and recall. Here, we used Arc/H1a catFISH imaging to address the contribution of the largely overlooked CA2 region to contextual learning by comparing ensemble codes across CA3, CA2, and CA1 in mice exposed to familiar, altered, and novel contexts. Further, to manipulate the quality of information arriving in CA2 we used two hippocampal mutant mouse lines, CA3-NR1 KOs and DG-NR1 KOs, that result in hippocampal CA3 neuronal activity that is uncoupled from the animal's sensory environment. Our data reveal largely coherent responses across the CA axis in control mice in purely novel or familiar contexts; however, in the mutant mice subject to these protocols the CA2 response becomes uncoupled from CA1 and CA3. Moreover, we show in wild-type mice that the CA2 ensemble is more sensitive than CA1 and CA3 to small changes in overall context. Our data suggest that CA2 may be tuned to remap in response to any conflict between stored and current experience.

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The rodent granular retrosplenial cortex (GRS) is reciprocally connected with the hippocampus. It is part of several networks implicated in spatial learning and memory, and is known to contain head-direction cells. There are, however, few specifics concerning the mechanisms and microcircuitry underlying its involvement in spatial and mnemonic functions. In this report, we set out to characterize intrinsic properties of a distinctive population of small pyramidal neurons in layer 2 of rat GRS. These neurons, as well as those in adjoining layer 3, were found to exhibit a late-spiking (LS) firing property. We established by multiple criteria that the LS property is a consequence of delayed rectifier and A-type potassium channels. These were identified as Kv1.1, Kv1.4 and Kv4.3 by Genechip analysis, in situ hybridization, single-cell reverse transcriptase-polymerase chain reaction, and pharmacological blockade. The LS property might facilitate comparison or integration of synaptic inputs during an interval delay, consistent with the proposed role of the GRS in memory-related processes.