A key subset of receptors involved in spinal-mediated biological rhythms

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*Biological rhythms underlie most vital functions in virtually all living organisms from plants to mammals. In vertebrate species, the circadian rhythm is probably, as of now, one the best characterized rhythmic functions. It involves the release of several chemicals such as gamma-aminobutyric acid, melatonin and serotonin (5-HT) that act specifically upon some of their receptor subtypes in the brain. With NSERC funding, my group has found evidence suggesting the existence of a partially comparable mechanism involved in the control of another rhythmic function that is locomotion. A few years ago, using pharmacological, surgical, and genetic approaches, we found indeed a key role as a trigger' of locomotor activity for a specific subtype (1A) of 5-HT receptors located in the lumbar spinal cord. We recently expanded those observations by providing additional evidence that other spinal-mediated rhythmic functions such as micturition, defecation and ejaculation critically depend also upon activation of 5-HT1A receptors. However, several important questions remain to be elucidated prior to understand fully the complex role of 5-HT in biological rhythms, specifically in the spinal cord. For instance, what role descending signals from brain or sensory signals from peripheral nerves play in spinal 5-HT1A receptor-mediated rhythms? What contributions other subtypes or families of receptors and their intracellular signals have in such spinal functions? These kinds of questions, addressed in my research program, are particularly exciting given their potential to unravel the details of this new role of 5-HT as a trigger' of neural oscillatory activities, in parallel to its more widely known role as a modulator' of neural functions. As such it will shed a new light on the complexity of 5-HT actions in vertebrate species generally inhibitory in the brain and apparently also excitatory in the spinal cord. It is not unreasonable to think that findings from the proposed research will eventually help other researchers revisiting the physiology of brain-mediated rhythmic functions such as sleeping, alertness, or hormonal release. I strongly believe that this research program will provide a rich and fruitful training experience for several graduate and undergraduate students here at Laval University.