Toward dissection of diverse neural components in the suprachiasmatic nucleus (SCN) pacemaker network

The suprachiasmatic nucleus (SCN), a central clock in the hypothalamus of mammals, consists of heterogeneous populations of neurons. The SCN expresses various neurotransmitters/neuropeptides and hundreds of other genes as detected by cell census studies including transcriptomics. Nonetheless, the SCN can sustain a precise ∼24 hr rhythm and acts as a central pacemaker to control daily rhythms of behavior and physiological processes throughout a lifespan. How does the SCN achieve this regularity in a network of ∼20,000 diverse cellular identities? Are there unique roles in individual SCN neurons or in subsets of SCN neurons? How are they classified, connected to sustain synchrony, and entrained to external light-dark cycles at the level of cell types? Only recently, the functional significance of individual oscillators in the SCN is beginning to be uncovered through the development and advancement of neurotechniques to target specific cell types for genetic manipulation and imaging. This review will summarize recent conditional knockout studies, focusing particularly on genetic drivers utilized in various experimental approaches. We will also discuss what questions lie ahead to disentangle the complexity of cellular components in the central pacemaker network. • •The Suprachiasmatic nucleus (SCN) consists of heterogeneous populations of neurons. • •Conditional strategies are powerful tools to examine roles of specific cells. • •Contributions of specific cellular oscillators have begun to be revealed. • •Further cell-type-specific studies will unravel the central pacemaking mechanism.