Global clock coordination by the SCN through relay and amplification of
diffusible and neural signaling
Abstract
The brain clock, located in the suprachiasmatic nucleus (SCN) of the
hypothalamus receives direct retinal input providing the entire body
with an internal representation of external solar time. The pathways by
which this small nucleus signals so broadly involve co-occurring nervous
and diffusible output signals, though the latter are less understood.
Portal pathways, such as the well-known pituitary portal pathway,
provide a mechanism whereby signals of neural origin can reach local,
specialized targets without suffering dilution in the systemic blood
supply. The newly discovered pathways involve direct connections between
each of the sensory circumventricular nuclei at their point of their
attachment to the brain. These nuclei line the brain’s ventricles, and
their leaky blood vessels and large perivascular spaces represent a
route whereby secretions from the SCN can be relayed and then amplified,
providing a pathway to achieve global coordination of circadian clock
signaling. This review provides a narrative that incorporates our
understanding of SCN neural and diffusible output signals, with
particular emphasis on the contribution of brain fluid compartments and
the fluids therein.