Department of Biology, Loyola University Chicago, Chicago, Illinois.
J Biol Rhythms. 2024 Oct;39(5):440-462. doi: 10.1177/07487304241263734. Epub 2024 Jul 26.
The circadian system coordinates multiple behavioral outputs to ensure proper temporal organization. Timing information underlying circadian regulation of behavior depends on a molecular circadian clock that operates within clock neurons in the brain. In and other organisms, clock neurons can be divided into several molecularly and functionally discrete subpopulations that form an interconnected central clock network. It is unknown how circadian signals are coherently generated by the clock network and transmitted across output circuits that connect clock cells to downstream neurons that regulate behavior. Here, we have exhaustively investigated the contribution of clock neuron subsets to the control of two prominent behavioral outputs in : locomotor activity and feeding. We have used cell-specific manipulations to eliminate molecular clock function or induce electrical silencing either broadly throughout the clock network or in specific subpopulations. We find that clock cell manipulations produce similar changes in locomotor activity and feeding, suggesting that overlapping central clock circuitry regulates these distinct behavioral outputs. Interestingly, the magnitude and nature of the effects depend on the clock subset targeted. Lateral clock neuron manipulations profoundly degrade the rhythmicity of feeding and activity. In contrast, dorsal clock neuron manipulations only subtly affect rhythmicity but produce pronounced changes in the distribution of activity and feeding across the day. These experiments expand our knowledge of clock regulation of activity rhythms and offer the first extensive characterization of central clock control of feeding rhythms. Despite similar effects of central clock cell disruptions on activity and feeding, we find that manipulations that prevent functional signaling in an identified output circuit preferentially degrade locomotor activity rhythms, leaving feeding rhythms relatively intact. This demonstrates that activity and feeding are indeed dissociable behaviors, and furthermore suggests that differential circadian control of these behaviors diverges in output circuits downstream of the clock network.
昼夜节律系统协调多种行为输出,以确保适当的时间组织。行为的昼夜节律调节的时间信息取决于在大脑中的时钟神经元内运行的分子生物钟。在 和其他生物体中,时钟神经元可以分为几个分子上和功能上离散的亚群,这些亚群形成了一个相互连接的中央时钟网络。目前尚不清楚时钟网络如何通过时钟网络一致地产生昼夜节律信号,并通过连接时钟细胞与调节行为的下游神经元的输出电路进行传输。在这里,我们详尽地研究了时钟神经元亚群对 两种主要行为输出的控制作用:运动活性和摄食。我们使用细胞特异性操作来消除分子时钟功能或广泛地在整个时钟网络或特定亚群中诱导电沉默。我们发现,时钟细胞操作会导致运动活性和摄食产生相似的变化,这表明重叠的中央时钟电路调节这些不同的行为输出。有趣的是,效应的幅度和性质取决于目标时钟亚群。侧向时钟神经元操作会严重降低摄食和活动的节律性。相比之下,背侧时钟神经元操作仅微妙地影响节律性,但会在一天中的活动和摄食分布上产生明显的变化。这些实验扩展了我们对时钟调节活动节律的认识,并提供了对中央时钟控制摄食节律的首次广泛特征描述。尽管中央时钟细胞破坏对活动和摄食有类似的影响,但我们发现,防止鉴定的输出电路中功能性信号的操作优先降低运动活性节律,而摄食节律相对完整。这表明活动和摄食确实是可分离的行为,并且进一步表明这些行为的差异昼夜节律控制在时钟网络下游的输出电路中是不同的。