The circadian clock: a tale of genetic–electrical interplay and synaptic integration

Pioneering work in Drosophila uncovered the building blocks of the molecular clock, consisting of transcription–translation feedback loops (TTFLs). Subsequent experimental work demonstrated that the mammalian TTFL is localized in cells and tissues throughout the brain and body. Further research established that neuronal activity forms an essential aspect of clock function. However, how the membrane electrical activity of clock neurons of the suprachiasmatic nucleus collaborate with the TTFL to drive circadian behaviors remains mostly unknown. Intercellular communication synchronizes the individual circadian oscillators to produce a precise and coherent circadian output. Here, we briefly review significant research that is increasing our understanding of the critical interactions between the TTFL and neuronal and glial activity in the generation of circadian timing signals.