Local circuit allowing hypothalamic control of hippocampal area CA2 activity and consequences for CA1

The hippocampus is critical for memory formation. The hypothalamic supramammillary nucleus (SuM) sends long-range projections to hippocampal area CA2. While the SuM-CA2 connection is critical for social memory, how this input acts on the local circuit is unknown. Using transgenic mice, we found that SuM axon stimulation elicited mixed excitatory and inhibitory responses in area CA2 pyramidal neurons (PNs). Parvalbumin-expressing basket cells were largely responsible for the feedforward inhibitory drive of SuM over area CA2. Inhibition recruited by the SuM input onto CA2 PNs increased the precision of action potential firing both in conditions of low and high cholinergic tone. Furthermore, SuM stimulation in area CA2 modulated CA1 activity, indicating that synchronized CA2 output drives a pulsed inhibition in area CA1. Hence, the network revealed here lays basis for understanding how SuM activity directly acts on the local hippocampal circuit to allow social memory encoding.

Automated summary

The study reveals that the hypothalamic supramammillary nucleus (SuM) influences the hippocampal area CA2 through a mix of excitatory and inhibitory responses. The inhibitory effect of SuM input is mediated largely by parvalbumin-expressing basket cells, enhancing the precision of action potential firing in CA2 pyramidal neurons and modulating CA1 activity. Synchronized output from CA2 drives pulsed inhibition in CA1, laying the foundation for understanding how SuM activity contributes to social memory encoding in the local hippocampal circuit.