Wiest Alyssa, Maurer John J, Beier Kevin T, Weber Franz, Chung Shinjae
Department of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Pharmacology Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
J Neurosci. 2025 Jul 2;45(27):e2146242025. doi: 10.1523/JNEUROSCI.2146-24.2025.
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 (CRH), similar to acute restraint stress, decreases sleep and impairs memory in a spatial object recognition task in male mice. Conversely, inhibiting CRH neurons during stress reduces stress-induced memory deficits while slightly increasing the amount of sleep. We found that both stress and stimulation of CRH neurons activate neurons in the lateral hypothalamus (LH) and that CRH projections to the LH regulate stress-induced memory deficits and sleep disruptions. Our results suggest that CRH neuronal 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.
应激对睡眠和记忆过程有深远影响。应激会损害记忆巩固,同样,睡眠中断也会损害记忆功能。然而,应激诱导的睡眠和记忆障碍背后的神经回路仍未完全了解。在此,我们表明,下丘脑室旁核促肾上腺皮质激素释放激素神经元(CRH)的激活,类似于急性束缚应激,会减少雄性小鼠的睡眠,并在空间物体识别任务中损害记忆。相反,在应激期间抑制CRH神经元可减少应激诱导的记忆缺陷,同时略微增加睡眠时间。我们发现,应激和CRH神经元的刺激都会激活下丘脑外侧区(LH)的神经元,并且CRH向LH的投射调节应激诱导的记忆缺陷和睡眠中断。我们的结果表明,CRH神经元通路调节应激对记忆和睡眠的不利影响——这是改善睡眠和缓解与应激相关疾病相关认知缺陷的重要一步。