Love and War: Control of Female Social Behaviors by the Hypothalamus

Citation

Liu, Mengyu (2024) Love and War: Control of Female Social Behaviors by the Hypothalamus. Dissertation (Ph.D.), California Institute of Technology. https://resolver.caltech.edu/CaltechTHESIS:01112024-021433003

Abstract

Aggressive and mating behaviors, crucial for survival, are inherently programmed in the brain and are orchestrated by genetically defined cell types within subcortical circuits. Despite the hard-wired nature, females exhibit a remarkable ability to flexibly adjust these behaviors to according to their reproductive states. The neural mechanisms governing the stable control and adaptive regulation of these behaviors remained unclear. Moreover, given the inherently complex and dynamic nature social interactions, the dynamics of the underlying motivational states and their encoding in the female brain was largely unknown.

Addressing these knowledge gaps in my thesis, I initially undertook a dissection of the subcortical circuits and genetically defined cell types involved in the control of female aggressive and mating behaviors. Using single-cell RNA sequencing and optogenetic perturbations, I identified distinct transcriptomic cell types in the ventromedial hypothalamus: α cells governing mating and ß cells regulating aggression. Furthermore, longitudinal monitoring of their activity during the transition from virginity to motherhood revealed that ß cells became more responsive to social cues, resulting a shift from mating to aggression. In a second line of investigation, I delved into the dynamics of female mating and its neural encoding. By monitoring single-cell activity in receptive females and applying dynamical system modeling to neural activity, I uncovered that α cell formed line attractor dynamics, encoding a sexual aroused state during mating. Additionally, longitudinal monitoring of activity across different hormonal states revealed population dynamics displaying receptivity state-dependent patterns across the estrus cycle. A third aspect of my research explored comprehensive changes in gene expression patterns in circuits influenced by hormones. Through comparative analysis of transcriptomic profiles in the ventromedial hypothalamus at different hormonal states. I identified qualitative changes in cell types within mating-activated α cells, correlated with sexual receptivity. These studies significantly contribute to our understanding of the neural basis controlling aggressive and mating behaviors, shedding light on their flexible regulation by physiological conditions in females.