Most of living organisms respond to daily changes in photoperiod by rhythmic adaptative alterations in physiological and behavioral states. In mammals, the suprachiasmatic nuclei (SCN) of the hypothalamus contain the neural clock for the generation and maintenance of circadian rhythms. Input to the SCN pacemaker is provided by direct and indirect retinal projections, and by a dense serotoninergic innervation from the raphe nuclei. It is well known that the neurotransmitter serotonin (5-HT) is a major participant in the regulation of the SCN activity either by influencing the endogenous clock or by modulating the retinal input. Many of the factors involved in the SCN 5-HT metabolism (content, synthesis activity, uptake) display circadian variation, pointing to a time dependent functional interaction between the pacemaker system and serotoninergic activity. The most important parameter regulating 5-HT function is the release of the amine. However, data concerning the circadian fluctuation in SCN 5-HT release are still lacking. For this reason, the first major objetive of this project is to define the diurnal fluctuation of 5-HT release in the SCN and its dependence on photoperiod by using in vivo microdialysis techniques.
Besides the light, several neurohumoral factors may influence the SCN pacemaker activity. One of them is the hormone melatonin, which is synthesized in the pineal gland during the darkenss in response to the SCN activity. Melatonin interacts with specific receptors located in the SCN and it is able to alter circadian rhythmicity. The mechanism mediating melatonin action on SCN is unknown, although an interaction with the serotoninergic system has been repeteadly proposed. With this basis, the second major objective of this proposal to study the role of the pineal gland and its hormone, melatonin, on the rhythm of 5-HT release in the SCN in vivo.