美国哈佛大学S. M. Dymecki团队揭示动态神经递质分离介导的适应光周期。相关论文于2024年7月17日在线发表在《自然》杂志上。

研究人员发现一个大脑回路和轴突分支特异性、可逆性神经递质释放系统，这对于行为和睡眠对光周期的适应至关重要。小鼠脑干中位缝核中的一种名为mrEn1-Pet1的神经元，将血清素和VGLUT3（SLC17A8，即谷氨酸的代理）分配到不同的轴突分支，这些分支支配昼夜节律和睡眠-觉醒时间的特定大脑区域。尽管这种分支特异性神经递质释放在光明和黑暗阶段没有区别，但在光周期变化时会重新组织。

在远离昼夜平分线条件的情况下，轴突小泡，而非细胞体，会改变神经化学表型，这些变化在返回昼夜平分线条件时被逆转。当研究人员在mrEn1-Pet1神经元中基因失活Vglut3时，睡眠-觉醒周期、自愿活动和时钟基因表达未能同步到新的光周期或同步延迟。结合交叉狂犬病毒追踪和投射特异性神经元沉默，研究人员描绘出一个从前视区到mrEn1-Pet1的连接，这一连接负责解码光周期输入，驱动神经递质重新组织，并促进行为同步。

这些研究结果揭示了一个调节生物体适应光周期变化的大脑回路和周期性、分支特异性神经递质释放系统。

据悉，昼夜节律变化（光周期）会改变生理和行为。对季节性光周期的适应性反应对所有生物都至关重要——调节失常与包括情感障碍和代谢综合征在内的疾病相关。昼夜节律回路在这种反应中起作用，但对于具体细胞基质如何同步光周期变化的机制了解甚少。

附：英文原文

Title: Adaptation to photoperiod via dynamic neurotransmitter segregation

Author: Maddaloni, G., Chang, Y. J., Senft, R. A., Dymecki, S. M.

Issue&Volume: 2024-07-17

Abstract: Changes in the amount of daylight (photoperiod) alter physiology and behaviour1,2. Adaptive responses to seasonal photoperiods are vital to all organisms—dysregulation associates with disease, including affective disorders3 and metabolic syndromes4. The circadian rhythm circuitry is implicated in such responses5,6, yet little is known about the precise cellular substrates that underlie phase synchronization to photoperiod change. Here we identify a brain circuit and system of axon branch-specific and reversible neurotransmitter deployment that are critical for behavioural and sleep adaptation to photoperiod. A type of neuron called mrEn1-Pet17 in the mouse brainstem median raphe nucleus segregates serotonin from VGLUT3 (also known as SLC17A8, a proxy for glutamate) to different axonal branches that innervate specific brain regions involved in circadian rhythm and sleep–wake timing8,9. This branch-specific neurotransmitter deployment did not distinguish between daylight and dark phase; however, it reorganized with change in photoperiod. Axonal boutons, but not cell soma, changed neurochemical phenotype upon a shift away from equinox light/dark conditions, and these changes were reversed upon return to equinox conditions. When we genetically disabled Vglut3 in mrEn1-Pet1 neurons, sleep–wake periods, voluntary activity and clock gene expression did not synchronize to the new photoperiod or were delayed. Combining intersectional rabies virus tracing and projection-specific neuronal silencing, we delineated a preoptic area-to-mrEn1Pet1 connection that was responsible for decoding the photoperiodic inputs, driving the neurotransmitter reorganization and promoting behavioural synchronization. Our results reveal a brain circuit and periodic, branch-specific neurotransmitter deployment that regulates organismal adaptation to photoperiod change.

DOI: 10.1038/s41586-024-07692-7

Source: https://www.nature.com/articles/s41586-024-07692-7