Browsing by Author "Smith, Victoria M"

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    Phase shifts to light are altered by antagonists to neuropeptide receptors
    (Elsevier, 2016-07-07) Chan, Ryan K; Sterniczuk, Roxanne; Enkhbold, Yaruuna; Jeffers, Ryan T; Basu, Priyoneel; Duong, Bryan; Chow, Sue-Len; Smith, Victoria M; Antle, Michael C
    The mammalian circadian clock in the suprachiasmatic nucleus (SCN) is a heterogeneous structure. Two key populations of cells that receive retinal input and are believed to participate in circadian responses to light are cells that contain vasoactive intestinal polypeptide (VIP) and gastrin-releasing peptide (GRP). VIP acts primarily through the VPAC2 receptor while GRP works primarily through the BB2 receptor. Both VIP and GRP phase shift the circadian clock in a manner similar to light when applied to the SCN, both in vivo and in vitro, indicating that they are sufficient to elicit photic-like phase shifts. However, it is not known if they are necessary signals for light to elicit phase shifts. Here we test the hypothesis that GRP and VIP are necessary signaling components for photic phase shifting the hamster circadian clock by testing two antagonists for each of these neuropeptides. The BB2 antagonist PD176252 had no effect on light-induced delays on its own, while the BB2 antagonist RC-3095 had the unexpected effect of significantly potentiating both phase delays and advances. Neither of the VIP antagonists ([D-p-Cl-Phe6, Leu17]-VIP, or PG99-465) altered phase shifting responses to light on its own. When the BB2 antagonist PD176252 and the VPAC2 antagonist PG99-465 were delivered together to the SCN, phase delays were significantly attenuated. These results indicate that photic phase shifting requires participation of either VIP or GRP, and only when signaling in both pathways is inhibited are phase shifts to light impaired. Additionally, the unexpected potentiation of light induced phase shifts by RC-3095 should be investigated further for potential chronobiotic applications.
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    Serotonergic enhancement of circadian responses to light: Role of the raphe and intergeniculate leaflet
    (Wiley, 2015-11) Smith, Victoria M; Jeffers, Ryan T; Antle, Michael C
    Light serves as the primary stimulus that synchronizes the circadian clock in the suprachiasmatic nucleus (SCN) to the external day-night cycle. Appropriately timed light exposure can reset the phase of the circadian clock. Some serotonergic drugs that bind to the 5-HT1A receptor can enhance phase shifts to light. The mechanism by which this potentiation occurs is not well understood. In this study we examine where in the hamster brain one of these drugs, BMY7378, might be working. Systemic (5 mg/kg), intradorsal raphe and intra-median raphe (both 15.6 nmol in 0.5 μl), but not intra-SCN (7.8 nmol or 15.6 nmol in 0.5 μl) injections of BMY7378 significantly potentiated phase shifts to light. Potentiation of photic shifts persisted when serotonergic innervation of the SCN was lesioned with infusions of the serotonin neurotoxin 5,7-dihydroxytryptamine into the SCN. Light-induced c-Fos expression in the rostral and caudal intergeniculate leaflet (IGL) was attenuated with systemic BMY7378, suggesting that the IGL may be involved in this response. Both complete IGL lesions and depletion of serotonergic innervation of the IGL prevented systemic BMY7378 from potentiating photic phase shifts. Together these findings suggest that the mechanism by which BMY7378 enhances photic responses is by changing the activity of the raphe nuclei to influence how the IGL responds to light, which subsequently influences the SCN as one of its downstream targets. Identification of the network that underlies this potentiation could lead to the development of useful therapeutic interventions for treating sleep and circadian disorders