Circadian Rhythms in Plasticity Markers Are Regulated by the Suprachiasmatic Nucleus and Local Circadian Oscillators in the Rodent Neocortex.

Circadian rhythms in clock gene expression are a global feature of neurons. While clock gene products have been shown to modulate plasticity at the synapse level, little is known about molecular circadian rhythms in neuroplasticity. In this study, we aim to establish circadian regulatory mechanisms of plasticity in the rat cerebral cortex. We show that the expression of the plasticity markers activity-regulated cytoskeleton-associated protein (Arc), brain-derived neurotrophic factor (Bdnf), and early growth response protein 1 (Egr1) exhibits marked circadian rhythms with increasing transcript levels during nighttime in the adult neocortex, but not in the hippocampus. Rhythmic expression of plasticity markers was restricted to postnatal stages. Lesion studies showed that rhythmic Arc, Bdnf, and Egr1 expression in the neocortex is regulated by the suprachiasmatic nucleus (SCN). High nocturnal Arc levels were partly restored by rhythmic subcutaneous infusion of corticosterone via an implanted programmable pump though without restoring rhythmic gene expression. Additionally, we show that the normal circadian Arc expression profile in the neocortex of cortex-specific Bmal1 clock gene knockout mice was disrupted compared to controls. In conclusion, our work suggests that the neuroplasticity of the neocortex exhibits circadian rhythmicity reflected by rhythmic plasticity markers controlled by a combination of the central clock of the SCN and the local circadian oscillator of the cerebral cortex.