Arc restores juvenile plasticity in adult mouse visual cortex

• Published in: Proceedings of the National Academy of Sciences - PNAS 2017-08, Vol.114 (34), p.9182-9187
• Main Authors: Jenks, Kyle R., Kim, Taekeun, Pastuzyn, Elissa D., Okuno, Hiroyuki, Taibi, Andrew V., Bito, Haruhiko, Bear, Mark F., Shepherd, Jason D.
• Format: Article
• Language: English
• Subjects: Age; Age Factors; Animals; ARC protein; Augmentation; Biological Sciences; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - physiology; Deprivation; Dominance, Ocular - genetics; Dominance, Ocular - physiology; Eye; Gene expression; Gene Expression Regulation, Developmental; Long-term depression; Long-Term Synaptic Depression - genetics; Long-Term Synaptic Depression - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Monocular vision; mRNA; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neuronal Plasticity - genetics; Neuronal Plasticity - physiology; Neuroplasticity; Ocular dominance; Protein biosynthesis; Protein synthesis; Ribonucleic acid; RNA; Rodents; Sensitivity; Studies; Visual cortex; Visual Cortex - growth & development; Visual Cortex - metabolism; Visual Cortex - physiology; Visual deprivation; Visual plasticity
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1700866114

The molecular basis for the decline in experience-dependent neural plasticity over age remains poorly understood. In visual cortex, the robust plasticity induced in juvenile mice by brief monocular deprivation during the critical period is abrogated by genetic deletion of Arc, an activity-dependent regulator of excitatory synaptic modification. Here, we report that augmenting Arc expression in adult mice prolongs juvenile-like plasticity in visual cortex, as assessed by recordings of ocular dominance (OD) plasticity in vivo. A distinguishing characteristic of juvenile OD plasticity is the weakening of deprived-eye responses, believed to be accounted for by the mechanisms of homosynaptic long-term depression (LTD). Accordingly, we also found increased LTD in visual cortex of adult mice with augmented Arc expression and impaired LTD in visual cortex of juvenile mice that lack Arc or have been treated in vivo with a protein synthesis inhibitor. Further, we found that although activity-dependent expression of Arc mRNA does not change with age, expression of Arc protein is maximal during the critical period and declines in adulthood. Finally, we show that acute augmentation of Arc expression in wild-type adult mouse visual cortex is sufficient to restore juvenile-like plasticity. Together, our findings suggest a unifying molecular explanation for the age- and activity-dependent modulation of synaptic sensitivity to deprivation.