Role of Hypothalamic CRH Neurons in Regulating the Impact of Stress on Memory and Sleep

Abstract

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 corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (CRHPVN), similar to acute restraint stress, decreases sleep and impairs memory in a spatial object recognition task in male mice. Conversely, inhibiting CRHPVNneurons during stress reduces stress-induced memory deficits while slightly increasing the amount of sleep. We found that both stress and stimulation of CRHPVNneurons activate neurons in the lateral hypothalamus (LH) and that CRHPVNprojections to the LH regulate stress-induced memory deficits and sleep disruptions. Our results suggest that CRHPVNneuronal pathways regulate the adverse effects of stress on memory and sleep—an important step toward improving sleep and ameliorating cognitive deficits associated with stress-related disorders.