How does cognition regulate innate “low-level” behaviors? While the cognitive functions of the prefrontal cortex (PFC) and hippocampus have been extensively studied, we know much less about their ability to regulate the activity of the various hypothalamic nuclei controlling motivated behaviors (sociability, aggression, mating, feeding). Living in society nonetheless requires that our past experiences and decision-making exert some degree of control over our “basic” behaviors. The lateral septum (LS) -receiving inputs from PFC and hippocampus and projecting primarily to the hypothalamus- is ideally positioned to integrate cognitive information and, in turn, regulate motivated behaviors. Thus I characterized in mice a novel circuit by which hippocampal CA2 projections to LS result in disinhibition of an aggression-promoting nucleus of the hypothalamus. I also showed that vasopressin enhances aggression through presynaptic facilitation of CA2 inputs to LS. Using this study as a blueprint, I will determine the logic by which LS integrates and compute cognitive inputs to regulate other motivated behaviors. As motivated behaviors depend on internal states, I will also explore how modulatory inputs (vasopressin, dopamine, serotonin) from subcortical brain regions to LS can regulate its function. Finally, since hippocampus, PFC and LS are implicated in several psychiatric disorders associated with altered social behaviors (schizophrenia, autism or bipolar disorder), insights into how these regions regulate motivated behaviors are critical for understanding both basic neural mechanisms as well as how disease processes lead to altered social interactions. This project therefore also aims to unravel potential changes occurring in disorders associated with social behavioral deficits with the ultimate goal of providing new therapeutic targets for disease treatment. Thus my study may suggest new approaches to treat abnormal social cognition associated with psychiatric disorders.
