Functional interactions between neurotransmitters and neuropeptides in regulating suprachiasmatic nucleus function and circadian rhythms

The overt expression of circadian rhythms is a manifestation of the suprachiasmatic nucleus (SCN). This integrated complex function based on the transcriptional/translational feedback loops (TFFLs), neurotransmitters, genes, networking, and synchronization is essential for this molecular mechanism to operate effectively. Neurotransmitters by participating in the entrainment to the environmental light conditions and synchronization contribute to the robustness of the rhythm. Neurotransmitter signaling is the hallmark of circadian rhythm expression. Even during development, neuropeptides contribute to the dramatic cellular, genetic, and network circuit changes. Participating neurotransmitters are seen in afferent inputs, efferent output, and the SCN. There are numerous neurotransmitters involved in SCN function. Astrocytes co-exist with neurons in the SCN. Autonomous clocks seen in astrocytes can drive circadian behavior like neurons. Astrocytes and neurons are acting as two arms of the clock. Coupling through glutamate released from astrocytes gives additional evidence for the role of astrocytes. Glutaminergic signaling from astrocytes may also be responsible for timekeeping. The neurotransmitters can independently and in combination execute the functions making SCN a unique pacemaker for the overt expression of circadian rhythms. This reassessment also highlights its role in underlying molecular mechanisms, genetic linkage, and the recently known role of astrocytes.