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.
Highlights
0 vCA1c0 vCA1c vCA1b vCA1a vDGHoechst Biocytin ChR2-eYFP ventral CA3 (vCA3) d 15 * 5 mV PSPmaxslm sr sp ventral CA1 (vCA1) so 25 ms Deep dorsal CA1 (dCA1) SR+CGP b vCA1a c SR+CGPControl vCA1a [9] dCA1 [7]
In contrast to the findings that dorsal CA2 (dCA2) produces a ~threefold larger EPSP in deep compared to superficial dorsal CA1 PNs21, we found no significant difference in the magnitude of the Postsynaptic potentials (PSPs) elicited by dCA2 inputs in deep compared to superficial vCA1a pyramidal neurons (PNs) using maximal intensity photostimulation, the magnitude of the dCA2-evoked PSP in vCA1a was approximately half that in deep dCA1 PNs (Fig. 6d)
To verify that clozapine N-oxide (CNO) injected into ventral HPC (vHPC) was acting locally and did not diffuse to dorsal HPC (dHPC) to silence dCA2 somatic output, we examined the effect of CNO infusion in vHPC on social aggression, which depends on arginine vasopressin 1b receptor (AVPR1b) expression in dCA222
Summary
To examine the importance of dCA2 during encoding/ consolidation, we performed a direct interaction test with a 24 h interval with CNO injected IP 30 min prior to trial 1 in mice that had been previously injected in dCA2 with AAV-DIO-hM4DiIRES-mCitrine (Fig. 2d). Amigo2-Cre and WT littermates were first injected with AAVDIO-hM4Di-IRES-mCitrine in dCA2 and after 3 weeks, injected with CNO IP 12 min after social memory encoding in trial 1 (Fig. 3f). Amigo2-Cre mice and WT littermates previously injected with AAV-DIO-hM4Di-IRES-mCitrine were both given CNO IP 30 min prior to the social discrimination trial (Fig. 4d). DCA2 provides strong excitatory drive to vCA1a PNs. To explore whether the projections from dCA2 to vCA1 form functional synapses, we injected the dCA2 region of Amigo2-Cre mice with AAV-DIO-ChR2-eYFP and, after 4 weeks, obtained acute slices from vHPC for electrophysiological recordings. The WT mice displayed intact a AAV-DIO-ChR2-eYFP injected in dCA2
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