【神经科学前沿技术培训系列】详见文末
责编︱王思珍
行为的节律性调控被认为是一个网络系统，主节律调控中枢视交叉上核（SCN）通过分泌分子或直接与间接的突触信号来协调局部或外周生物钟。然而，生物钟已经被证明对感觉输入的敏感性呈现昼夜节律性，并且这种节律性调控不依赖于SCN。因此，昼夜节律网络可能包含中间级别的“节点”，这些节点在组织跨脑区的分子和行为节律中起着关键作用。该研究揭示了，adLAmWAKE神经元作为这种“中间”级别生物钟发挥着重要作用。这些细胞不仅能够在SCN丧失功能的情况下维持其节律性，还能够调节其他大脑子区域的节律。此外，adLAmWAKE神经元不仅调控单一行为，还能够协调多种相互关联的昼夜节律行为。鉴于mWAKE基因在多个存在局部生物钟的大脑区域中表达，该分子可能广泛定义了具有内在节律性的局部脑区生物钟，从而在大脑中协调昼夜节律相关行为和信息传递。
严军（研究组组长、高级研究员，中国科学院神经科学研究所）
This paper recently published in Neuron by Liu et al. in Mark Wu’s lab represents an exciting advancement in our understanding the neural-circuit mechanism of circadian clock controlled behaviors, particularly in its identification of a discrete extra-SCN brain oscillator in the lateral amygdala (LA). The LA is often regarded as the “sensory gateway” to the amygdala, a key region for emotional processing. Interestingly, their study identified an extra-SCN brain oscillator in the anterior dorsal LA marked by mWAKE gene (adLAmWAKE). The mWAKE gene was previously discovered by Mark Wu’s lab as the mouse homolog of WAKE gene in drosophila that was considered to label clock neurons through a series of studies. The current study suggested that adLAmWAKE neurons dictate the rhythms of a behavioral module, namely, the external touch/pain perception and an internal state (anxiety) via distinct circuit projections and mWAKE-dependent up-regulation of BK channels. These findings revealed an elegant mechanism by which a brain oscillator promotes increased anxiety and reduced sensory perception during the day when mice seek shelter to sleep, but reduced anxiety and increased touch perception during the night when mice are active and exploring the environment. They found that molecular rhythms of the adLAmWAKE oscillator are markedly influenced by a fear-inducing odor, suggesting that this local clock mechanism can be entrained by external cues. Together, these findings defined a new extra-SCN brain oscillators at the cellular level and uncovered the molecular and circuit mechanisms by which the clock organizes sensory perception and internal states.
The work by Liu et al. is truly groundbreaking, as it defines a new mechanism by which behaviors can be regulated by circadian clocks outside the primary pacemaker (suprachiasmatic nucleus). Specifically, they show that a fear-inducing odor can entrain a local oscillator in the amygdala, providing a pathway for modular, hierarchical control of distinct behaviors. I was impressed by the level of mechanistic detail that the authors achieved in defining this process, and believe the findings will have a major impact on the field.
李小军（教授，西安交通大学前沿科学技术研究院）
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