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Phase Regulation of the SCN Circadian Clock: Serotonergic and Neuropeptidergic Mechanisms

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2009, PHD, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
Timing of the mammalian circadian clock, the suprachiasmatic nucleus (SCN) is regulated by photic and nonphotic entraining inputs. Photic inputs reach the SCN from the retinohypothalamic tract (RHT) utilizing glutamate as neurotransmitter, which activates the retinorecipient cells of the SCN in part by release of gastrin releasing peptide (GRP). Nonphotic inputs reach the SCN from the raphe nuclei and the intergeniculate leaflet utilizing serotonin (5-HT) and neuropeptide Y (NPY) as neurotransmitters respectively. Efferent signaling of the SCN to target areas involves arginine vasopressin (AVP). Brief (~2 day) constant light exposure (LLb), significantly enhances phase resetting responses to 5-HT1A,7 agonist 8-OH-DPAT and other nonphotic stimuli. The present study was undertaken to determine if LLb exposure can amplify phase resetting responses to endogenous 5-HT and accelerate re-entrainment responses to large magnitude phase advance shifts of the light/dark (LD) cycle. Endogenous 5-HT activity was increased by systemic administration of 5-HT precursor L-tryptophan and reuptake inhibitor fluoxetine. In hamsters exposed to LLb phase shifting responses to stimulated endogenous 5-HT were significantly enhanced compared to those under LD. LLb exposure also had significant potentiating effect on rhythm re-entrainment response to 8-OH-DPAT. Hamsters exposed to LLb and 8-OH-DPAT re-entrained faster to a 10 hour phase advance shift of the LD cycle compared to the vehicle or LD controls. Further, analysis of distinct daily rhythms of the SCN peptidergic activity and effect of serotonergic activation on them was studied. Sensitive microdialysis-radioimmunoassay procedure was used to explore the regulatory role of 5-HT on AVP and GRP release from the SCN. In hamsters housed under 14:10 LD, AVP exhibited daily fluctuations of release with levels increasing during the morning to peak around mid subjective day. This pattern persists under constant darkness confirming the circadian nature of the AVP release. Synaptic release was confirmed by reverse microdialysis with calcium channel blockers and depolarizing agents. Reverse microdialysis with 8-OH-DPAT during the subjective day, significantly suppressed the SCN GRP release but had little effect on AVP. Overall, potentiation of serotonergic phase resetting response by LLb offers a potential approach for treatment of circadian related desynchronies. The interactions between serotonergic and peptidergic systems of the SCN are important in determining the phase of the SCN activity in response to LLb and other stimuli.
J. David Glass, PhD (Advisor)
E.M Mintz, PhD (Committee Member)
S.L. Veney, PhD (Committee Member)
M.A. Raghanti, PhD (Committee Member)
S.B. Fountain, PhD (Committee Member)
122 p.

Recommended Citations

Citations

  • Kaur, G. (2009). Phase Regulation of the SCN Circadian Clock: Serotonergic and Neuropeptidergic Mechanisms [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1257518311

    APA Style (7th edition)

  • Kaur, Gagandeep. Phase Regulation of the SCN Circadian Clock: Serotonergic and Neuropeptidergic Mechanisms. 2009. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1257518311.

    MLA Style (8th edition)

  • Kaur, Gagandeep. "Phase Regulation of the SCN Circadian Clock: Serotonergic and Neuropeptidergic Mechanisms." Doctoral dissertation, Kent State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=kent1257518311

    Chicago Manual of Style (17th edition)