Waksman Institute, Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854.
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Proc Natl Acad Sci U S A. 2021 Mar 9;118(10). doi: 10.1073/pnas.2019826118.
Regulation of circadian behavior and physiology by the brain clock requires communication from central clock neurons to downstream output regions, but the mechanism by which clock cells regulate downstream targets is not known. We show here that the pars intercerebralis (PI), previously identified as a target of the morning cells in the clock network, also receives input from evening cells. We determined that morning and evening clock neurons have time-of-day-dependent connectivity to the PI, which is regulated by specific peptides as well as by fast neurotransmitters. Interestingly, PI cells that secrete the peptide DH44, and control rest:activity rhythms, are inhibited by clock inputs while insulin-producing cells (IPCs) are activated, indicating that the same clock cells can use different mechanisms to drive cycling in output neurons. Inputs of morning cells to IPCs are relevant for the circadian rhythm of feeding, reinforcing the role of the PI as a circadian relay that controls multiple behavioral outputs. Our findings provide mechanisms by which clock neurons signal to nonclock cells to drive rhythms of behavior.
大脑时钟对昼夜节律行为和生理的调节需要中枢时钟神经元向下游输出区域传递信号，但时钟细胞调节下游靶标的机制尚不清楚。我们在这里表明，脑间部（PI）以前被确定为时钟网络中晨型细胞的靶标，也接收夜型细胞的输入。我们确定晨型和夜型时钟神经元与 PI 具有时间依赖性的连接，这种连接受到特定肽以及快速神经递质的调节。有趣的是，分泌肽 DH44 并控制休息-活动节律的 PI 细胞被时钟输入抑制，而胰岛素分泌细胞（IPCs）被激活，这表明相同的时钟细胞可以使用不同的机制来驱动输出神经元的循环。晨型细胞对 IPCs 的输入与摄食的昼夜节律有关，这进一步证实了 PI 作为一个控制多种行为输出的生物钟中继的作用。我们的发现为时钟神经元向非时钟细胞发出信号以驱动行为节律提供了机制。
