Intracellular Recording Lab, Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, P.O. Box 76198-13159, Kerman, Iran.
Laboratory of Emotions Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteur Street 3, 02-093, Warsaw, Poland.
Sci Rep. 2023 Apr 12;13(1):6011. doi: 10.1038/s41598-023-33016-2.
Exposure to prenatal stress (PS) leads to the offspring's vulnerability towards the development of cognitive and behavioral disorders. Laterodorsal tegmentum (LDT) is a part of the brainstem cholinergic system that is believed to play a pivotal role in the stress-associated progression of anxiety, memory impairment, and addictive behaviors. In this study, we aimed to investigate the electrophysiological alterations of LDT cholinergic neurons and its accompanied behavioral and cognitive outcomes in the offspring of mice exposed to physical or psychological PS. Swiss Webster mice were exposed to physical or psychological stress on the tenth day of gestation. Ex vivo investigations in LDT brain slices of adolescent male offspring were performed to evaluate the effects of two stressor types on the activity of cholinergic neurons. Open field test, elevated plus maze, passive avoidance test, and conditioned place preference were conducted to assess behavioral and cognitive alterations in the offspring. The offspring of both physical and psychological PS-exposed mice exhibited increased locomotor activity, anxiety-like behavior, memory impairment, and preference to morphine. In both early- and late-firing cholinergic neurons of the LDT, stressed groups demonstrated higher firing frequency, lower adaptation ratio, decreased action potential threshold, and therefore increased excitability compared to the control group. The findings of the present study suggest that the hyperexcitability of the cholinergic neurons of LDT might be involved in the development of PS-associated anxiety-like behaviors, drug seeking, and memory impairment.
产前应激（PS）暴露会导致后代易患认知和行为障碍。外侧背盖核（LDT）是脑桥胆碱能系统的一部分，被认为在与应激相关的焦虑、记忆障碍和成瘾行为的进展中起着关键作用。在这项研究中，我们旨在研究暴露于物理或心理 PS 的小鼠后代的 LDT 胆碱能神经元的电生理改变及其伴随的行为和认知结果。在妊娠第 10 天，瑞士 Webster 小鼠暴露于物理或心理应激下。对青春期雄性后代的 LDT 脑片进行离体研究，以评估两种应激源类型对胆碱能神经元活性的影响。在后代中进行旷场试验、高架十字迷宫试验、被动回避试验和条件性位置偏爱试验，以评估行为和认知改变。物理和心理 PS 暴露的后代的活动增加，焦虑样行为，记忆障碍和对吗啡的偏好。与对照组相比，LDT 的早发和晚发胆碱能神经元的应激组表现出更高的放电频率、更低的适应比、降低的动作电位阈值，因此兴奋性增加。本研究的结果表明，LDT 胆碱能神经元的过度兴奋可能参与了 PS 相关的焦虑样行为、觅药和记忆障碍的发展。
