Hypothalamic neuronal plasticity drives response to social experience

ongoing

The ability to learn and adapt in response to diverse social experiences is fundamental for animal survival. While key defensive actions against social threats such as flight or fight are innate, previous social experience can guide the selection of the appropriate response to minimize future harm, such as the development of social avoidance following social defeat. The ventromedial hypothalamus is a key brain structure in the innate defensive system, and activity in its ventrolateral part (VMHvl) can mediate both social aggression and escape, yet how previous experience influences hypothalamic social threat processing is not understood. Recent evidence has shown that social defeat can promote functional reorganization of neural activity in this structure, but the mechanisms of such plasticity have not been studied. In this project proposal, I plan to systematically investigate experience-dependent synaptic and neuronal plasticity in the VMHvl. First, I will use state-of-the-art in vitro electrophysiological techniques in mice to comprehensively explore changes in synaptic transmission in this region following social defeat. Second, I will leverage a recently developed calcium imaging method combined with optogenetics to follow and manipulate synaptic plasticity in the freely behaving mouse. Together with ethological behavior quantification techniques, this approach will allow me to identify and causally test the in vivo functional consequences of defeat-induced plasticity in the VMHvl. If successful, this project will provide novel insights into the synaptic and circuit basis of hypothalamic adaptations to social defeat. Gaining a mechanistic and physiological understanding of neuroadaptations following social experiences will offer new targets for therapeutic manipulation of maladaptive responses to social adversity that underlie many psychiatric disorders and pose a significant public health challenge.