A hypothalamic circuit mechanism underlying the impact of stress on memory and sleep

Stress profoundly affects sleep and memory processes. Stress impairs memory consolidation, and similarly, disruptions in sleep compromise memory functions. Yet, the neural circuits underlying stress-induced sleep and memory disturbances are still not fully understood. Here, we show that activation of CRH ^PVN neurons, similar to acute restraint stress, decreases sleep and impairs memory in a spatial object recognition task. Conversely, inhibiting CRH ^PVN neurons during stress reverses stress-induced memory deficits while slightly increasing the amount of sleep. We found that both stress and stimulation of CRH ^PVN neurons activate neurons in the lateral hypothalamus (LH), and that their projections to the LH are critical for mediating stress-induced memory deficits and sleep disruptions. Our results suggest a pivotal role for CRH ^PVN neuronal pathways in regulating the adverse effects of stress on memory and sleep, an important step towards improving sleep and ameliorating the cognitive deficits that occur in stress-related disorders.