Sleep is essential for healthy mind and body. It is regulated by homeostasis, by which accumulated sleep drive during wakefulness leads to increased propensity toward sleep. However, we can stay up late if we have something important or interesting to do, for example, take care of a baby or read a fascinating book. In other words, sleep is also regulated by motivational states. Thus sleep drive competes with other motivational drives to decide whether we sleep or engage in other important or interesting activities. We have recently shown that sex drive profoundly affects male sleep in Drosophila and that a subset of octopaminergic neurons (octopamine is analogous to human norepinephrine) mediates sleep suppression by male sex drive. Previous studies have shown that female flies sleep less and lay more eggs after mating. Thus both males and females adjust their sleep patterns to meet reproductive needs. However, the neural mechanisms of how sleep and reproductive behaviors are balanced are not well understood. In preliminary studies for this proposal, we identified several previously uncharacterized neuronal populations for balancing sleep and reproductive behaviors in males and females. Two of the newly identified populations are dopaminergic, suggesting that octopamine and dopamine signaling pathways cooperate to integrate sleep and reproductive behaviors. We will determine the anatomical and physiological connectivity among the various neuronal populations, and investigate their role in sleep and reproductive behaviors using a combination of behavioral analysis, calcium imaging, circuit tracing, immunohistochemistry, and generation of new drivers for precise manipulation of specific neurons. Our proposed studies offer an excellent opportunity to discover basic neural mechanisms and general organizing principles that underlie the balance between competing drives. Investigating how sleep regulatory mechanisms communicate with neural mechanisms for sexually-dimorphic behaviors using neuromodulators such as octopamine and dopamine may lead to a better understanding of how the human brain integrates sleep drive and other motivational states.
Sleep disorders are especially common among older people and neurological patients, and negatively impact the quality of life of both patients and their caregivers. Although sex differences in sleep have been documented, the underlying differences in neural mechanisms are not well understood. The proposed studies will elucidate sexually-dimorphic regulation of sleep and may lead to novel approaches for treating sleep disorders that take sex differences into account.
