Circadian rhythmicity in the primary mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus, is maintained by transcriptional and translational feedback loops involving the gene Per1. This gene is important for the entrainment or synchronization of circadian rhythms to the light-dark cycle. During photic stimulation, retinal terminals synapse onto neurons in the ventral SCN that contain gastrin releasing peptide (GRP). These neurons express Per1 in response to photic stimulation, while vasopressin- containing neurons in the dorsal region rhythmically express Per1. Given that GRP application to the SCN produces phase shifts, the current proposal will investigate whether photic entraining signals are mediated from retinorecipient cells to rhythm-generating clock cells by GRP. Using a Per1::GFP (green fluorescent protein) transgenic mouse, this proposal will characterize Per1-expressing cells in response to GRP application, and determine whether GRP receptor activation is sufficient and necessary to induce Per1 gene activity. This research investigating the role of SCN peptides in photic synchronization of circadian rhythms may lead to the development of treatments for circadian disruptions in mood and developmental disorders. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32NS051183-01A2
Application #
7114650
Study Section
Special Emphasis Panel (ZRG1-F03A-M (20))
Program Officer
Mitler, Merrill
Project Start
2006-09-01
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
1
Fiscal Year
2006
Total Cost
$45,976
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Paul, Jodi R; Munir, Hira A; van Groen, Thomas et al. (2018) Behavioral and SCN neurophysiological disruption in the Tg-SwDI mouse model of Alzheimer's disease. Neurobiol Dis 114:194-200
Albers, H Elliott; Walton, James C; Gamble, Karen L et al. (2017) The dynamics of GABA signaling: Revelations from the circadian pacemaker in the suprachiasmatic nucleus. Front Neuroendocrinol 44:35-82
Besing, Rachel C; Paul, Jodi R; Hablitz, Lauren M et al. (2015) Circadian rhythmicity of active GSK3 isoforms modulates molecular clock gene rhythms in the suprachiasmatic nucleus. J Biol Rhythms 30:155-60
Kudo, Takashi; Tahara, Yu; Gamble, Karen L et al. (2013) Vasoactive intestinal peptide produces long-lasting changes in neural activity in the suprachiasmatic nucleus. J Neurophysiol 110:1097-106
Gamble, Karen L; Ciarleglio, Christopher M (2009) Ryanodine receptors are regulated by the circadian clock and implicated in gating photic entrainment. J Neurosci 29:11717-9
Gamble, Karen L; Allen, Gregg C; Zhou, Tongrong et al. (2007) Gastrin-releasing peptide mediates light-like resetting of the suprachiasmatic nucleus circadian pacemaker through cAMP response element-binding protein and Per1 activation. J Neurosci 27:12078-87