Stress-activated neuronal ensemble in the supramammillary nucleus stores anxiety but not memory

Anxiety is a very common negative emotional status induced by stress. However, its underlying neural mechanism is still largely unknown. Here, we found a hypothalamic section named the supramammillary nucleus (SuM), which is taking control of anxiety. We then characterized a small ensemble of stress-activated neurons and recruited encoding anxiety. These stress-activated neurons specifically respond to stress, and its activation robustly increases the anxiety-like behavior of mice without significantly influencing fear memory. We then found that the ventral subiculum -SuM but not the dorsal subiculum -SuM projection encodes anxiety and would exhibit an anti-anxiety effect by its inhibition. Our findings extend the understanding of the function of the neuronal engram cells and bring new insights into the studies on emotion especially anxiety.