TIMEKEEPING AND SYNC REQUIRE CONTINUED
VIP SIGNALLING
The
suprachiasmatic nucleus (SCN) is a small and sexually dimorphic neuronal group
in the chiasmatic region of the hypothalamus, where its cells are traditionally
divided into two principal parts: a ventrolateral subdivision characterized by
neurons immunoreactive for vasoactive intestinal polypeptide (VIP), and a dorsomedial
subdivision immunoreactive for arginine vasopressin (AVP). SCN appears to be
the neural substrate for day-night cycles in body temperature, plasma
concentration of many hormones, motor activity, renal secretion, sleeping and
waking, and many other physiological parameters.
SCN
is considered the circadian clock of the whole body, which neurons spontaneously
synchronize so that their target cells in peripheral tissues receive correctly
time-coordinated signals. But how do the synchronizers stay in sync?
A
new research by Maywood E. S. and colleagues sheds light on the mechanism
underlying synchronization and maintenance of timekeeping in suprachiasmatic circadian
clock (Synchronization and maintenance of
timekeeping in suprachiasmatic circadian clock cells by neuropeptidergic
signaling. Curr. Biol. 16, 599-605, 2006).
VIP
signalling in SCN ventrolateral subdivision had previously been implicated in circadian
rhytmicity, so Maywood’s team investigated this
association by looking at expression of the clock gene period (Per)
in mice that lacked VIP receptor 2 (VIPR2). In wild mice, Per expression
is temporally controlled by a feedback mechanism that results in a 24-hour periodicity
between expression peaks. The group used a Per1
transgene containing a bio-luminescent reporter and,
in real time, measured the amount of light emitted from SCN slices in culture
over a number of days. Compared with wild-type mice, VIPR2 lacking mice showed
low-levels of bioluminescence and an imprecise periodicity. Therefore, loss of
VIP-signalling reduced Per expression and disrupted interneuronal
synchronicity.
In
further experiments Maywood and his co-workers demonstrated that Per
expression and synchronicity depended on depolarization.
In fact, as depolarization
ceased, over a period of days, neurons lost sync and Per
expression levels dropped.
The
findings indicate that synchronicity of SCN neurons requires continued VIP
signalling and neurons continually signal to each other to maintain synchronicity.