the natural day-night cycle. The primary synchronization cue is the
daily cycle of day and night, sunrise and sunset, light and dark.
What is the cellular and molecular nature of the biological clock—the
ticking mechanism—the generator of the rhythmic signals that pre-
sumably tell us when to be tired, when to sleep, and when to be awake
and alert? And where in the body is the endogenous clock located?
After decades of research, we now know the primary locus of the
circadian clock (at least in vertebrates) to be a cluster of cells located
in the hypothalamus of the diencephalon, at the top of the brainstem.
The particular cell cluster is called the suprachiasmatic nucleus, or
SCN. The name derives from its location, which is immediately above
(supra) the optic chiasm, the junction of the two optic nerves coming
into the thalamus from the retinas of the left and right eyes. Like all
brain structures, the SCN is bilaterally symmetric: there are two of
them, located close together within the hypothalamus.
The human SCN contains around twenty thousand neurons, many
of which exhibit a circadian periodicity of neural firing. Experiments
have also been conducted in which clusters of neurons from the SCN
are removed from an animal’s brain and the cells are kept alive for up
to several days by placing them in an appropriate nutrient environ-
ment. Under such conditions, the circadian periodicity of neuronal
activity in SCN cells continues, independent of any connection with
the rest of the brain or body.
Is it possible to trace the ticktock mechanism of the biological
clock all the way to the level of individual cells? Molecular-genetic
insight into the mechanism of the biological clock took a great leap
forward in the 1970s with the discovery of a gene mutation in the
fruit fly Drosophila that had substantial effects on the period of a fly’s
circadian rhythm: a mutation in a gene called PER, for period. Years of