All vertebrates synthesize the hormone melatonin in their pineal gland at night. This nocturnal signal helps to synchronize aspects of circadian biology; signaling to the various organs of the body what time of day it is and, given that day length in non-equatorial zones changes over the annual cycle, what season it is. Thus, a vertebrate's physiology adjusts appropriately to the time of day or year. In many vertebrates, the melatonin signal is used to time the onset of reproductive activity. If there is no synchronization of the various tissues in the body, then serious behavioral and physiological disruption can occur. A uniquely human example of this is jet-lag; after flying across different time zones rapidly, there is asynchrony in the timing of activity in different internal organs. As a result, in the short-term there is a general feeling of morbidity, but constant jet-lag can have seriously detrimental health effects; including deficiencies in brain functions like cognition. This proposal builds on preliminary data supporting the novel idea that the brain itself can synthesize melatonin independently of the pineal gland, and explores novel pathways in the brain via which this brain-derived melatonin might be acting, especially as relates to seasonal reproduction. Resulting data will expand our understanding of how the vertebrate brain works in general, and how circadian biology and reproduction are regulated by this novel pathway. The findings will have broad implications for basic biology, conservation biology, animal husbandry and human health.
Photoperiodism in all vertebrates tested involves integration of the circadian system with the reproductive system. As a result, it is not surprising that mammals use the melatonin signal to decode the length of the day, along with its direction of change, and regulate their reproductive responses. What is surprising is that birds possess this elegant time-keeping system and yet are thought not to use it to regulate the timing of their reproductive photoperiodic responses. Thus, the function of the nightly release of melatonin in birds is unknown with respect to reproduction. The problem with the above dogma in birds is that all studies have focused on traditional sources of melatonin, the pineal gland and the retina. What if the avian hypothalamus itself is responsive to light and can synthesize melatonin according to the prevailing day length? This proposal provides strong preliminary data indicating that the avian brain can synthesize melatonin de novo, and does so independently of sensory organs such as the eyes or pineal gland. Thus, neurally-derived melatonin, and not melatonin from other sources, may well be a key component of the photoperiodic machinery in birds. Specifically, we aim to demonstrate de novo melatonin synthesis by the avian brain, explore its regulation, identify neural pathways that neurally-derived melatonin interacts with, and eventually determine its role in reproduction and other aspects of physiology. Demonstration that the brain can synthesize melatonin de novo is entirely novel and has implications for all vertebrate neuroendocrine processes, including in humans. This work is funded by the Neural Systems Cluster (NSC) with support from the Behavioral Systems Cluster (BSC), in the Integrative Organismal Systems in the Directorate for Biological Sciences.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
