Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261.
Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, PA 15213.
Proc Natl Acad Sci U S A. 2021 Apr 27;118(17). doi: 10.1073/pnas.2101818118.
Neuropeptides control rhythmic behaviors, but the timing and location of their release within circuits is unknown. Here, imaging in the brain shows that synaptic neuropeptide release by clock neurons is diurnal, peaking at times of day that were not anticipated by prior electrical and Ca data. Furthermore, hours before peak synaptic neuropeptide release, neuropeptide release occurs at the soma, a neuronal compartment that has not been implicated in peptidergic transmission. The timing disparity between release at the soma and terminals results from independent and compartmentalized mechanisms for daily rhythmic release: consistent with conventional electrical activity-triggered synaptic transmission, terminals require Ca influx, while somatic neuropeptide release is triggered by the biochemical signal IP Upon disrupting the somatic mechanism, the rhythm of terminal release and locomotor activity period are unaffected, but the number of flies with rhythmic behavior and sleep-wake balance are reduced. These results support the conclusion that somatic neuropeptide release controls specific features of clock neuron-dependent behaviors. Thus, compartment-specific mechanisms within individual clock neurons produce temporally and spatially partitioned neuropeptide release to expand the peptidergic connectome underlying daily rhythmic behaviors.
神经肽控制着节律性行为，但它们在回路中的释放时间和位置尚不清楚。在这里，对大脑的成像显示，时钟神经元的突触神经肽释放具有昼夜节律性，峰值出现在一天中之前的电和 Ca 数据所没有预期到的时间。此外，在峰值突触神经肽释放前几个小时，神经肽就会在神经元胞体中释放，而胞体一直未被认为与肽能传递有关。胞体和末端释放之间的时间差异源于每日节律性释放的独立和分区机制：与传统的电活动触发的突触传递一致，末端需要 Ca 内流，而体细胞神经肽释放则由生化信号 IP 触发。破坏了胞体机制后，末端释放和运动活动周期的节律不受影响，但具有节律行为和睡眠-觉醒平衡的果蝇数量减少。这些结果支持了这样的结论，即体细胞神经肽释放控制着时钟神经元依赖性行为的特定特征。因此，单个时钟神经元内的特定于隔室的机制产生了时间和空间分区的神经肽释放，以扩展基础日常节律行为的肽能连接组。
