Phenotype and function of raphe projections to the suprachiasmatic nucleus

Authors

  • Glenn R. Yamakawa,

    1. Brain and Cognitive Sciences Research Group, Department of Psychology, 2500 University Drive NW, University of Calgary, Calgary, AB T2N 1N4, Canada
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  • Michael C. Antle

    1. Brain and Cognitive Sciences Research Group, Department of Psychology, 2500 University Drive NW, University of Calgary, Calgary, AB T2N 1N4, Canada
    2. Hotchkiss Brain Institute and Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada
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Dr M. C. Antle, Brain and Cognitive Sciences Research Group, as above.
E-mail: antlem@ucalgary.ca

Abstract

The circadian clock, located in the suprachiasmatic nucleus (SCN), receives a major afferent from the median raphe nucleus (MRN). In the Syrian hamster, only about 50% of the cells giving rise to this afferent contain serotonin. There is mixed evidence as to whether the serotonergic portion of this projection is involved in non-photic phase shifting of circadian locomotor rhythms. In order to better characterize the non-serotonergic projections, we conducted retrograde tract tracing using the beta subunit of cholera toxin combined with multi-label immunohistochemistry. Similar to previous findings, almost half of the retrogradely labeled cells contained serotonin. Additionally, approximately 30% of the retrogradely labeled cells contained vesicular glutamate transporter 3 (VGLUT3), but not serotonin. Surprisingly, some dorsal raphe cholera toxin labeling was also noted, particularly in animals with central-SCN injections. To determine if the non-serotonergic projections were important for non-photic phase shifts elicited by MRN stimulation, the MRN was electrically stimulated in animals pretreated with SCN injection of either the serotonin neurotoxin 5,7-dihydroxytryptamine or vehicle control. Intact animals phase advanced to midday electrical stimulation of the raphe while lesioned animals did not. Together, these results show that although some of the non-serotonergic raphe projections to the SCN contain VGLUT3, it is the serotonergic raphe innervation of the SCN that is critical for non-photic phase shifting elicited by MRN stimulation.

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