Regulating the Suprachiasmatic Nucleus (SCN) Circadian Clockwork: Interplay between Cell-Autonomous and Circuit-Level Mechanisms

Jan 5, 2017Cold Spring Harbor perspectives in biology

How Internal Cell Processes and Network Interactions Work Together to Control the Brain's Daily Clock

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Abstract

The suprachiasmatic nucleus (SCN) contains approximately 20,000 neurons that work together to regulate daily cycles of behavior and physiology.

SCN neurons possess an internal clock that operates independently but relies on circuit-level interactions for synchronization.
Neuropeptide signaling plays a crucial role in synchronizing SCN neurons, influenced by the molecular clockwork and rhythmic electrical activity.
Daytime norepinephrine drive and nighttime potassium drag are essential for maintaining the SCN's rhythmic activity.
Identifying specific neuronal groups in the SCN reveals their pacemaking roles, indicating a complex interaction in timekeeping.
Current research aims to clarify the computations involved in timing information processing within the SCN and its relationship with other circadian clocks in the brain.

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The suprachiasmatic nucleus (SCN) is the principal circadian clock of the brain, directing daily cycles of behavior and physiology. SCN neurons contain a cell-autonomous transcription-based clockwork but, in turn, circuit-level interactions synchronize the 20,000 or so SCN neurons into a robust and coherent daily timer. Synchronization requires neuropeptide signaling, regulated by a reciprocal interdependence between the molecular clockwork and rhythmic electrical activity, which in turn depends on a daytime Nadrive and nighttime Kdrag. Recent studies exploiting intersectional genetics have started to identify the pacemaking roles of particular neuronal groups in the SCN. They support the idea that timekeeping involves nonlinear and hierarchical computations that create and incorporate timing information through the interactions between key groups of neurons within the SCN circuit. The field is now poised to elucidate these computations, their underlying cellular mechanisms, and how the SCN clock interacts with subordinate circadian clocks across the brain to determine the timing and efficiency of the sleep-wake cycle, and how perturbations of this coherence contribute to neurological and psychiatric illness. + +

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Regulating the Suprachiasmatic Nucleus (SCN) Circadian Clockwork: Interplay between Cell-Autonomous and Circuit-Level Mechanisms

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