The nonapeptide vasopressin has multiple functions as a hormone in the periphery (e.g. to maintain the osmotic homeostasis), but also functions as a neurotransmitter in the brain (e.g. to mediate emotions and various forms of social behavior; Neumann & Landgraf, 2012). Recently, our knowledge on the latter was extended by Ludwig and colleagues demonstrating that social olfactory cues are processed by an intrinsic vasopressin system in the olfactory bulb (Tobin et al. 2010). This study showed that even in well‐studied systems new discoveries are still to be made when one looks closely enough with the proper techniques. And that is what Ludwig and colleagues continued to do in the current study, reported in this issue of The Journal of Physiology, where they have moved their focus from the nose to the eyes. Tsuji et al. (2017) were able to identify and, more importantly, to further characterize a new physiological mechanism that shows how the perception of light through the eyes impacts on the circadian rhythm in rats; and vasopressin is the main player.
Vasopressin is known to be synthesized within and released from neurons of the hypothalamic suprachiasmatic nucleus (SCN), the internal clock of the mammalian brain that enforces – and thereby ensures – a 24 h biological rhythm (Kalsbeek et al. 2010). In order to properly function as the circadian clock, the SCN requires information on the current light intensity of the environment. This information is signalled to the SCN from photo‐sensitive (due to the photo‐pigment melanopsin) glutamatergic neurons originating in the retina of the eyes, i.e. the retinal ganglion cells (RGCs). Tsuji et al. (2017) have now discovered in rats a subpopulation of RGCs that express vasopressin. By employing a number of complementary techniques including a transgenic rat line, adenoviral vectors, in vitro and in vivo electrophysiology and microdialysis, the authors characterized the physiological function of the vasopressinergic neurons of the RGC. The result is that, when stimulated with light, these RGCs release vasopressin into the SCN and, in this way, control the vasopressin output of the SCN, as well as the expression of genes relevant for photo‐entrainment of circadian rhythms. Interestingly, even in primitive animals the conserved co‐occurence of opsin with vasotocin (Tessmar‐Raible et al. 2007), which is homologous to vasopressin, suggests a primordial minimal ‘module’ to secrete vasotocin in response to changes in light conditions. Hence, the existence of such cells and their function might represent a mechanism that is present in most, if not all, animals.
In addition to the above‐mentioned findings, Tsuji et al. (2017) were also able to reveal that the light‐induced vasopressin release from the RGCs is especially prominent at the end of the night, but not the end of the day. Due to this physiological specificity, the response of the SCN neurons to light gets enhanced. The discovery of such a mechanism is striking, given the fact that disrupted vasopressin signalling within the SCN results in a rapid phase‐shift to a new light–dark rhythm, as demonstrated in mice with a double‐knockout for vasopressin receptors V1a and V1b (Yamaguchi et al. 2013). These mice were described as being resistant to jet lag, a physiological state in which the biological clock is not synchronized with the actual external day–night cycle.
Most of us have experienced jet lag, e.g. when travelling between continents or working in rotating shifts. The physiological effects of jet lag on our life can be quite negative, ranging from sleep disturbances to gastrointestinal and cardiovascular problems. To fight against jet lag, the most common treatment is to manipulate the sleep–wake cycle either by forcing oneself to go to sleep (or to stay awake) or to pharmacologically intervene against the sleep disturbances. The new data from Tsuji et al. (2017) in rats not only provides further background on the physiological mechanisms regarding the retina–SCN connection for the perception of the ambient light situation, but may also open new possibilities for treating jet lag in a different way. Given that the vasopressinergic RGC neurons with the same physiological properties are also present in humans, a new route for manipulating the circadian functions of the hypothalamic SCN from the periphery may have been revealed. Hence, pharmacological manipulation of the vasopressin signalling from the eye to the SCN could help to promptly reset the biological clock to the ambient time. One might think of an easy‐to‐use application in the form of eye drops. Imagine how convenient it would be to get rid of jet lag after a long intercontinental flight just by dripping a few drops in your eyes, so that your biological clock is reset to the current time zone. As we have no time to spare in modern society, we could start our business meeting or, maybe even more importantly, our holiday right away without feeling jet lagged.
Additional information
Competing interests
The author declares that there are no conflicts of interest.
Linked articles This Perspective highlights an article by Tsuji et al. To read this article, visit https://doi.org/10.1113/JP274025.
This is an Editor's Choice article from the 1 June 2017 issue.
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