+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Copper chelation and exogenous copper affect circadian clock phase resetting in the suprachiasmatic nucleus in vitro



Copper chelation and exogenous copper affect circadian clock phase resetting in the suprachiasmatic nucleus in vitro



Neuroscience 256: 252-261



Light stimulates specialized retinal ganglion cells to release glutamate (Glu) onto circadian clock neurons of the suprachiasmatic nucleus (SCN). Glu resets the phase of the SCN circadian clock by activating N-methyl-d-aspartate receptors (NMDAR) causing either delays or advances in the clock phase, depending on early- or late-night stimulation, respectively. In addition, these Glu-induced phase shifts require tropomyosin receptor kinase B (TrkB) receptor activity. Previous studies show that copper (Cu) released at hippocampal synapses can inhibit NMDAR activity, and application of exogenous Cu likewise inhibits NMDAR activity. We investigated the effects of Cu in acute SCN brain slices prepared from C57BL/6Nhsd adult, male mice using treatments that decrease or increase available Cu levels in vitro and recorded neuronal activity on the following day. When bath-applied for 10 min at zeitgeber time (ZT) 16 (where ZT0=lights-on in the donor animal colony), the Cu-specific chelators tetrathiomolybdate (TTM) and bathocuproine disulfonate each induce ∼2.5-3-h phase delays in circadian neuronal activity rhythms, similarly to Glu-induced phase delays. Co-application of 10 μM CuCl2, but not 10 μM CoCl₂ blocks TTM-induced phase delays. Furthermore, TTM causes phase advances when applied at ZT23. At both application times, TTM-induced phase shifts are blocked by NMDA or TrkB receptor antagonists. Surprisingly, bath-application of 10 μM Cu alone also induces phase shifts in analogous experiments at ZT16 and ZT23. Inhibiting NMDAR does not block Cu-induced phase shifts. TrkB inhibition blocks Cu-induced phase delays but not phase advances. Thus, increasing and decreasing Cu availability appear to shift the SCN clock phase through different mechanisms, at least at the receptor level. We propose that Cu plays a role in the SCN circadian clock by modulating Glu signaling.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 052344732

Download citation: RISBibTeXText

PMID: 24161278

DOI: 10.1016/j.neuroscience.2013.10.033


Related references

Role of GABA in resetting the circadian clock in the suprachiasmatic nucleus. Journal of Neurochemistry 74(Suppl ): S46, 2000

In vivo resetting of the hamster circadian clock by 5-HT7 receptors in the suprachiasmatic nucleus. Journal of Neuroscience 21(14): 5351-5357, 2001

In Vivo Resetting of the Hamster Circadian Clock by 5-Ht 7 Receptors in the Suprachiasmatic Nucleus. The Journal of Neuroscience 21(14): 5351-5357, 2001

Midbrain raphe modulation of nonphotic circadian clock resetting and 5-HT release in the mammalian suprachiasmatic nucleus. Journal of Neuroscience 23(20): 7451-7460, 2003

Activation of AMPA receptors in the suprachiasmatic nucleus phase-shifts the mouse circadian clock in vivo and in vitro. Plos one 5(6): E10951, 2010

Sensitivity and selectivity of in vitro serotonergic resetting of the mammalian suprachiasmatic circadian clock. Society for Neuroscience Abstracts 16(2): 1256, 1990

Copper in the suprachiasmatic circadian clock: A possible link between multiple circadian oscillators. European Journal of Neuroscience 2018:, 2018

Serotonergic pre-treatments block in vitro serotonergic phase shifts of the mouse suprachiasmatic nucleus circadian clock. Neuroscience 142(2): 547-555, 2006

Phase differences in expression of circadian clock genes in the central nucleus of the amygdala, dentate gyrus, and suprachiasmatic nucleus in the rat. Plos one 9(7): E103309, 2014

Activation of MT(2) melatonin receptors in rat suprachiasmatic nucleus phase advances the circadian clock. American Journal of Physiology. Cell Physiology 280(1): C110-C118, 2001

Activation of MT2 melatonin receptors in rat suprachiasmatic nucleus phase advances the circadian clock. American Journal of Physiology 280(1): 10-C118, 2001

Resetting the suprachiasmatic nucleus clock. Frontiers in Bioscience 9: 56-62, 2004

Resetting the circadian clock in the suprachiasmatic brain slice. Society for Neuroscience Abstracts 11(2): 818, 1985

Fluoxetine modulates the circadian biological clock via phase advances of suprachiasmatic nucleus neuronal firing. Biological Psychiatry 60(8): 896-899, 2006

Dark pulse resetting of the suprachiasmatic clock in Syrian hamsters: behavioral phase-shifts and clock gene expression. Neuroscience 127(2): 529-537, 2004