Wiest Alyssa, Maurer John J, Weber Franz, Chung Shinjae
Department of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Pharmacology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
bioRxiv. 2024 Oct 18:2024.10.17.618467. doi: 10.1101/2024.10.17.618467.
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 neurons, similar to acute restraint stress, decreases sleep and impairs memory in a spatial object recognition task. Conversely, inhibiting CRH neurons during stress reverses 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 their projections to the LH are critical for mediating stress-induced memory deficits and sleep disruptions. Our results suggest a pivotal role for CRH 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.
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明确。在此，我们表明，促肾上腺皮质激素释放激素（CRH）神经元的激活与急性束缚应激类似，会减少睡眠，并损害空间物体识别任务中的记忆。相反，在应激期间抑制CRH神经元可逆转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，并且它们向LH的投射对于介导应激诱导的记忆缺陷和睡眠中断至关重要。我们的研究结果表明，CRH神经元通路在调节应激对记忆和睡眠的不利影响方面起着关键作用，这是改善睡眠和缓解应激相关疾病中出现的认知缺陷的重要一步。
