Seeing the forest and trees: whole-body and whole-brain imaging for circadian biology.
Recent advances in methods for making mammalian organs translucent have made possible whole-body fluorescent imaging with single-cell resolution. Because organ-clearing methods can be used to image the heterogeneous nature of cell populations, they are powerful tools to investigate the hierarchical organization of the cellular circadian clock, and how the clock synchronizes a variety of physiological activities. In particular, methods compatible with genetically encoded fluorescent reporters have the potential to detect circadian activity in different brain regions and the circadian-phase distribution across the whole body. In this review, we summarize the current methods and strategy for making organs translucent (removal of lipids, decolourization of haemoglobin and adjusting the refractive index of the specimen). We then discuss possible applications to circadian biology. For example, the coupling of circadian rhythms among different brain regions, brain activity in sleep-wake cycles and the role of migrating cells such as immune cells and cancer cells in chronopharmacology.
Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Quantitative Biology Center, RIKEN, Osaka, Japan.
K L
KL
Ode
Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Quantitative Biology Center, RIKEN, Osaka, Japan.
H R
HR
Ueda
D000818:Animals; D001683:Biological Clocks / Q000502:physiology; D001921:Brain / Q000502:physiology*; D019454:Chronotherapy / Q000379:methods; D057906:Circadian Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D006652:Histological Techniques / Q000379:methods; D006801:Humans; D000069416:Intravital Microscopy / Q000379:methods*; D008322:Mammals / Q000502:physiology; D008856:Microscopy, Fluorescence / Q000379:methods; D059906:Neuroimaging / Q000379:methods*; D012894:Sleep Stages / Q000502:physiology; D014851:Wakefulness / Q000502:physiology; D051598:Whole Body Imaging / Q000379:methods*
light-sheet microscope; single-cell resolution; tissue clearing