Bioluminescence imaging of Arc expression enables detection of activity-dependent and plastic changes in the visual cortex of adult mice

Abstract

Induction of the activity-regulated cytoskeleton-associated protein gene (Arc), one of the immediate early genes, in the brain correlates with various sensory processes, natural behaviors, and pathological conditions. Arc is also involved in synaptic plasticity during development. Thus, in vivo monitoring of Arc expression is useful for the analysis of physiological and pathological conditions in the brain. Recently, in vivo imaging of Arc expression using various green fluorescent protein-based probes has been reported; however, these probes can only be applied for the detection of fluorescence signals from superficial layers of the cortex with some autofluorescence noise. Here, we generated a novel transgenic mouse strain to monitor the neuronal-activity-dependent Arc expression using bioluminescence signals in vivo. Because of the very high sensitivity with a high signal-to-noise ratio, we detected neuronal-activity-dependent plastic changes in the bioluminescence signal intensity in the mouse visual cortex after visual deprivation, suggesting structural plasticity after peripheral lesions in adults. We also detected drastic changes in bioluminescence signals after seizure induction with kainic acid. Our novel mouse strain will be valuable for the continuous monitoring of neuronal-activity-dependent Arc expression in the brain under physiological and pathological conditions.

Application of hairless mouse strain to bioluminescence imaging of Arc expression in mouse brain

“…Acute treatment with KA is often carried out to produce a neurodegenerative disease model using laboratory animals and also induces Arc expression through synaptic activation. We reported the continuous increase in Arc - Luc expression level over 6 h after KA injection at the adult stage [11]. Here, we extend the examination of the temporal pattern of KA-induced Arc expression in the Arc - Luc Tg HL mice at 4 weeks of age (Fig.…”

“…Previously, we successfully generated Arc - Luc Tg mice for the BLI of Arc expression [11]. However, the genetic background of the Arc - Luc Tg mice is C57BL/6, and the black fur and skin pigmentation of this strain attenuate photon emission at various developmental stages (Fig.…”

“…We previously reported the activity-dependent and plastic changes in Arc expression in the visual cortex of adult Arc - Luc Tg mice [11]. In this experiment, we extended the application of Arc - Luc Tg HL mice to continuous imaging at an interval of less than 7 days.…”

“…Previously, we established a novel reporter transgenic (Tg) mouse strain, namely, Arc - Luc Tg mice, in which the firefly luciferase gene ( Luc ) is driven by the Arc promoter [11]. Arc , that is, the activity-regulated cytoskeleton-associated protein gene, is one of the immediate early genes (IEGs), which are highly responsive to various external stimuli in the central nervous system (CNS) [12, 13].…”

“…However, its black fur, skin pigmentation, and hair regrowth after depilation interfere with BLI during development. Thus, the periods of BLI were restricted less than 24 h and at an interval of more than 4 weeks [11]. …”