October 24, 2020

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

The hippocampus is critical for memory formation. Area CA2 has been shown to contribute to several essential brain functions including social novelty discrimination, sharp-wave ripple initiation and spatial encoding. The supramammillary nucleus (SuM) sends long-range projections to area CA2, is active during novelty exposure, and the SuM-CA2 connection has recently been shown to be important for social novelty discrimination. However, the properties and targets of the SuM input in CA2 are unknown. Using optogenetics, we found that stimulation of SuM axons elicited mixed excitatory and inhibitory responses in area CA2 pyramidal neurons (PNs). We examined the strength of the SuM excitatory input to interneurons in area CA2 and identified parvalbumin-expressing basket cells as responsible for the feedforward inhibitory drive of SuM over area CA2. We demonstrated that inhibition recruited by the SuM input onto area CA2 PNs increased the precision of their action potential firing both in conditions of low and high cholinergic tone. Furthermore, we observed a clear modulation of CA1 activity with SuM stimulation in area CA2 in vivo and in slice, 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.

 bioRxiv Subject Collection: Neuroscience

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