Serotonin (5-HT) has important regulatory actions within the mammalian circadian systems including modulation of photic signaling in the suprachiasmatic nucleus (SCN) and non-photic phase resetting of the circadian clock. The long- term objective of the proposed studies is to explore the neural mechanisms underlying the physiological control of 5-HT within the circadian clock. The specific goal of this research proposal is to examine the circadian regulation of 5-HT within the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN), and explore possible DRN-MRN serotonergic interactions. Brain microdialysis will first be used to assess the daily rhythm of 5-HT release in the DRN and MRN. To determine time-of-day differences in 5-HT1a somatodendritic autoreceptor-mediated control of basal SCN 5-HT release, brain microdialysis and intracerebral microinjection methodologies will be combined. Lastly, a combination of brain microdialysis, electrical stimulation and intracerebral microinjection techniques will be used to characterize the site and receptor subtype involved in the blockade of DRN-stimulated 5-HT release in the SCN. These data will bring us closer to developing therapeutic strategies for alleviating human neurological disorders involving disruption of serotonergic function and desynchronization of the circadian clock.
