of intracellular calcium levels in SCN neurons may be driven by circadian clock gene expression.
Circadian clock gene expression and intracellular calcium levels exhibit autonomous circadian rhythms in SCN neurons.
Intracellular calcium rhythms are typically weaker than the rhythms of clock gene expression in dispersed SCN cells.
In SCN slice cultures, both clock gene and calcium rhythms are stronger compared to dispersed cells.
Blocking neuronal firing in slice cultures weakens calcium rhythms but does not affect rhythms in dispersed cells.
The phase relationship between calcium levels and clock gene rhythms varies more in slice cultures than in dispersed cells.
Both calcium and clock gene rhythms are abolished in SCN cells lacking the essential clock gene.
Simplified
of mammalian physiology and behavior are coordinated by the suprachiasmatic nucleus (SCN) in the hypothalamus. Within SCN neurons, various aspects of cell physiology exhibit circadian oscillations, including circadian clock gene expression, levels of intracellular Ca([Ca]), and neuronal firing rate. [Ca]oscillates in SCN neurons even in the absence of neuronal firing. To determine the causal relationship between circadian clock gene expression and [Ca]rhythms in the SCN, as well as the SCN neuronal network dependence of [Ca]rhythms, we introduced GCaMP3, a genetically encoded fluorescent Caindicator, into SCN neurons from ::LUC knock-in reporter mice. Then, PER2 and [Ca]were imaged in SCN dispersed and organotypic slice cultures. In dispersed cells, PER2 and [Ca]both exhibited cell autonomous circadian rhythms, but [Ca]rhythms were typically weaker than PER2 rhythms. This result matches the predictions of a detailed mathematical model in which clock gene rhythms drive [Ca]rhythms. As predicted by the model, PER2 and [Ca]rhythms were both stronger in SCN slices than in dispersed cells and were weakened by blocking neuronal firing in slices but not in dispersed cells. The phase relationship between [Ca]and PER2 rhythms was more variable in cells within slices than in dispersed cells. Both PER2 and [Ca]rhythms were abolished in SCN cells deficient in the essential clock gene. These results suggest that the circadian rhythm of [Ca]in SCN neurons is cell autonomous and dependent on clock gene rhythms, but reinforced and modulated by a synchronized SCN neuronal network. 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ i i i i i i i i i i i i Bmal1
Key numbers
80 of 100
Cellular Rhythmicity
Percentage of cells with significant rhythms in dispersed cultures.
40 of 100
Calcium Rhythmicity
Percentage of cells with significant [Ca] rhythms in dispersed cultures.
71%
Increased Rhythmicity in Slices
Percentage of cells with rhythmic [Ca] in SCN slice cultures.
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