Visual cortical circuits show profound plasticity during early life and are later stabilized by molecular "brakes" limiting excessive rewiring beyond a critical period. The mechanisms coordinating the expression of these factors during the transition from development to adulthood remain unknown. We found that miR-29a expression in the visual cortex dramatically increases with age, but it is not experience-dependent. Precocious high levels of miR-29a blocked ocular dominance plasticity and caused an early appearance of perineuronal nets. Conversely, inhibition of miR-29a in adult mice using LNA antagomirs activated ocular dominance plasticity, reduced perineuronal nets, and restored their juvenile chemical composition. Activated adult plasticity had the typical functional and proteomic signature of critical period plasticity. Transcriptomic and proteomic studies indicated that miR-29a manipulation regulates the expression of plasticity brakes in specific cortical circuits. These data indicate that miR-29a is a regulator of the plasticity brakes promoting age-dependent stabilization of visual cortical connections.
- Klíčová slova
- DNA methylation, microRNA, ocular dominance plasticity, perineuronal net,
- MeSH
- mikro RNA * genetika MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neuroplasticita genetika MeSH
- oční dominance genetika MeSH
- proteomika MeSH
- zrakové korové centrum * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- mikro RNA * MeSH
- MIRN29 microRNA, mouse MeSH Prohlížeč
Life span and aging are substantially modified by natural selection. Across species, higher extrinsic (environmentally related) mortality (and hence shorter life expectancy) selects for the evolution of more rapid aging. However, among populations within species, high extrinsic mortality can lead to extended life span and slower aging as a consequence of condition-dependent survival. Using within-species contrasts of eight natural populations of Nothobranchius fishes in common garden experiments, we demonstrate that populations originating from dry regions (with short life expectancy) had shorter intrinsic life spans and a greater increase in mortality with age, more pronounced cellular and physiological deterioration (oxidative damage, tumor load), and a faster decline in fertility than populations from wetter regions. This parallel intraspecific divergence in life span and aging was not associated with divergence in early life history (rapid growth, maturation) or pace-of-life syndrome (high metabolic rates, active behavior). Variability across four study species suggests that a combination of different aging and life-history traits conformed with or contradicted the predictions for each species. These findings demonstrate that variation in life span and functional decline among natural populations are linked, genetically underpinned, and can evolve relatively rapidly.
- Klíčová slova
- Intraspecific variation *, life span *, neoplasia *, pace-of-life syndrome *, parallel evolution *, reproductive senescence *,
- MeSH
- biologická evoluce * MeSH
- Cyprinodontiformes genetika fyziologie MeSH
- dlouhověkost MeSH
- podnebí MeSH
- selekce (genetika) * MeSH
- stárnutí * MeSH
- zvířata MeSH
- zvláštnosti životní historie * MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
