A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics

Abstract

Recent results suggest that social memory requires the dorsal hippocampal CA2 region as well as a subset of ventral CA1 neurons. However, it is unclear whether dorsal CA2 and ventral CA1 represent parallel or sequential circuits. Moreover, because evidence implicating CA2 in social memory comes largely from long-term inactivation experiments, the dynamic role of CA2 in social memory remains unclear. Here, we use pharmacogenetics and optogenetics in mice to acutely and reversibly silence dorsal CA2 and its projections to ventral hippocampus. We show that dorsal CA2 activity is critical for encoding, consolidation, and recall phases of social memory. Moreover, dorsal CA2 contributes to social memory by providing strong excitatory input to the same subregion of ventral CA1 that contains the subset of neurons implicated in social memory. Thus, our studies provide new insights into a dorsal CA2 to ventral CA1 circuit whose dynamic activity is necessary for social memory.

Oxytocin and vasopressin in the rodent hippocampus

“…However, modest levels of social discrimination persist with inhibition of dorsal CA2/CA3 inputs to caudal dorsal CA1, which the authors suggest may be due to insufficient illumination or incomplete inhibition . Chemogenetic silencing of dorsal CA2 inputs to the ventral CA1 via local infusions of clozapine‐n‐oxide robustly impairs social memory, further supporting a dorsal CA2 to ventral CA1 circuit underlying social memory. The CA1 also receives monosynaptic input from the EC, however, optical inhibition of this pathway in the ventral CA1 region does not impair social recognition, suggesting information transfer from the CA2/CA3 region is more important for this task.…”

“…Regarding outputs from the CA1 region in the context of social memory, optogenetic inhibition of ventral CA1 terminals forming synapses onto the nucleus accumbens impairs the storage of conspecific information . Furthermore, dorsal CA2 neurons preferentially project to the same ventral CA1 region , supporting a social memory circuit involving dorsal CA2‐ventral CA1‐nucleus accumbens. Overall, it appears that social information is processed in all subfields of the hippocampus, with the ventral CA3, dorsal CA2 and ventral CA1 regions being of critical importance to social memory.…”

“…Indeed, excitotoxic lesions aimed at the CA2 region, genetically‐targeted chronic inhibition of the dorsal CA2 region, and acute chemogenetic or optogenetic silencing of the dorsal CA2 region all impair social memory in male mice. Acute manipulations of CA2 cell activity indicate that this area is critical for the encoding, consolidation, and recall phases of social memory . Furthermore, replacement of Avpr1b expression in the CA2 region of male Avpr1b knockout mice restores aggressive behavior, confirming that this brain region also contributes to social aggression as well.…”

“…This Oxtr‐induced change in intrinsic excitability involves a combination of both phospholipase C‐dependent inhibition of KCNQ channels, affecting the resting membrane potential, and phospholipase C‐ or protein kinase C‐dependent changes in action potential shape . Both mechanisms, working in concert with Oxtr‐dependent enhancement of GABAergic transmission in the CA2 region (see below), promote intense short bursts of CA2 principal cells that is expected to favor robust and precise transfer of social information to downstream CA1 targets . The Oxtr‐mediated enhancement of both CA2 intrinsic excitability and excitatory input illustrate the profound modulatory effect Oxt exerts on an important component of the social memory circuit.…”

Vaccinia‐related kinase 2 plays a critical role in microglia‐mediated synapse elimination during neurodevelopment

“…However, during the probe test without a platform on Day 6, WT mice traveled more in the target quadrant than the VRK2 KO mice (Figure f). According to previous reports, social memory, contextual freezing behavior, and Morris water maze memory are dependent on the hippocampus (Meira et al, ; Morris, Garrud, Rawlins, & O'Keefe, ; Phillips & LeDoux, ). From these behavioral test results, we conclude that adult VRK2 KO mice have impairments in behaviors that involve the hippocampus.…”