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.