The cell adhesion molecule EphA4 is involved in circadian clock functions

• Published in: Genes, brain and behavior Vol. 17; no. 1; pp. 82 - 92
• Main Authors: Kiessling, S., O'Callaghan, E. K., Freyburger, M., Cermakian, N., Mongrain, V.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-01-2018; John Wiley & Sons, Inc
• Subjects: Animals; Astrocytes; Biological clocks; c-Fos protein; Cell adhesion & migration; Cell Adhesion - physiology; Cell adhesion molecules; Cell adhesion protein; circadian clock; Circadian Clocks - genetics; Circadian Clocks - physiology; Circadian rhythm; Circadian Rhythm - physiology; Circadian rhythms; c‐FOS; endogenous circadian period; EphA4; EphA4 protein; Female; Light; light entrainment; light pulse; locomotor activity rhythm; Male; Mice; Mice, Knockout; Motor Activity - physiology; Neurons - metabolism; Osteosarcoma; PER1; Photic Stimulation; Physical Conditioning, Animal; Proto-Oncogene Proteins c-fos - metabolism; Receptor, EphA4 - genetics; Receptor, EphA4 - metabolism; Receptor, EphA4 - physiology; Running; Suprachiasmatic nucleus; Suprachiasmatic Nucleus - metabolism; Suprachiasmatic Nucleus - physiology; Synaptic plasticity; EphA4; PER1; Cell adhesion protein; light pulse; locomotor activity rhythm; c-FOS; endogenous circadian period; circadian rhythms; suprachiasmatic nucleus; circadian clock; light entrainment
• ISSN: 1601-1848; 1601-183X
• DOI: 10.1111/gbb.12387

Circadian (∼24 h) rhythms of cellular network plasticity in the central circadian clock, the suprachiasmatic nucleus (SCN), have been described. The neuronal network in the SCN regulates photic resetting of the circadian clock as well as stability of the circadian system during both entrained and constant conditions. EphA4, a cell adhesion molecule regulating synaptic plasticity by controlling connections of neurons and astrocytes, is expressed in the SCN. To address whether EphA4 plays a role in circadian photoreception and influences the neuronal network of the SCN, we have analyzed circadian wheel‐running behavior of EphA4 knockout (EphA4−/−) mice under different light conditions and upon photic resetting, as well as their light‐induced protein response in the SCN. EphA4−/− mice exhibited reduced wheel‐running activity, longer endogenous periods under constant darkness and shorter periods under constant light conditions, suggesting an effect of EphA4 on SCN function. Moreover, EphA4−/− mice exhibited suppressed phase delays of their wheel‐running activity following a light pulse during the beginning of the subjective night (CT15). Accordingly, light‐induced c‐FOS (FBJ murine osteosarcoma viral oncogene homolog) expression was diminished. Our results suggest a circadian role for EphA4 in the SCN neuronal network, affecting the circadian system and contributing to the circadian response to light.
The EphA4−/− mice exhibited reduced photic phase shifting behavior, which was accompanied by a reduction in light‐induced proteins in the suprachiasmatic nucleus.