Neural critical periods
Neural critical periods are limited life stages in which the plasticity of neural connections is maximal, and the brain’s development adapts to the environment. Researchers from Scuola Normale Superiore in Pisa and Leibniz Institute on Aging (FLI) in Jena have discovered the role of small microRNAs (miR-29) in these learning-dependent plasticity stages. First miR-29 concentration in young mice blocks cortical plasticity, whereas blocking miR-29 in adult animals induces plasticity typical for more first sensitive stages. Plasticity indicates that miR-29 is an age-dependent modulator of developmental plasticity.
After birth, the brain’s prenatal development characterize by a transient and functional high plasticity window (a critical or sensitive period). Certain areas of the brain develop further through some maturation and differentiation processes, where neural connections rapidly create and increase the plasticity of the brain. Infants’ natural language acquisition is the best-known example of this sensitive stage.
Neuroplasticity gives our brains the ability to adapt to the new needs of our lives. However, often this is limit in the adult brain, making the learning process more difficult. To identify the cellular and molecular mechanisms which open and close these sensitive steps associated with aging. Researchers at Scuola Normale Superiore (SNS) in Pisa, Italy, worked with Jena’s Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), with Germany. Other members studied the plasticity of the visual cortex in mice.
Plasticity of the visual cortex
“The neural network in the visual cortex maximally adapted to visual stimuli in sensitive developmental stages, which allows us to identify important regulators of brain plasticity,” said Alessandro Cellerino, senior author of a study published EMBO report, SNS and FLI in Jena. Group leader and Professor Tommaso Pizzorusso of the University of Florence and NRC Neuroscience Institute in Pisa. One paradigm assumes that the plasticity of ocular dominance passively declines with age. Anyway, it becomes increasingly clear that the level of plasticity set on the coordinated action of age- and experience-dependent molecular processes that actively promote or inhibit circuit plasticity.
“The visual cortical circuits that are part of the visual system and enable vision,” explains Professor Cellerino, “they exhibit strong plasticity during their early life and are later stabilized by molecular brakes that limit the over-adaptation of the link beyond the critical period.”. However, the underlying mechanisms that regulate these factors’ expression during the transition from development to adult are still unknown.
MiR-29-Age-Dependent Control of Visual Cortical Plasticity
The researchers analyzed miRNA/RNA datasets in the visual cortex of developing mice to identify the factors that regulate the visual cortex’s postnatal development. They compared them at different time points: P10, ten days after birth, just before opening the eyes and the onset of the sensitive phase, and P28, when the mouse cortex reached functional maturity.
Their results showed that the microRNA family miR-29 is an age-dependent modulator of developmental plasticity in the visual cortex. “The 30-fold increase in miR-29a was the most highly upregulate miRNA at the sensitive stage,” explains Professor Cellerino of FLI/SNS. Regulation of the miR-29 family remarkably conserved in fish, mice, and humans. More than half of the targets regulated by miR-29 downregulate with age, including significant brain regulators plasticity. And also This indicates that miR-29a is an essential regulator of downstream developmental processes.
Further analysis showed that an early increase in miR-29a concentration in young mice blocked young ocular dominant plasticity and caused the perineal network. PPN is an impressive structure in the central nervous system responsible for synaptic stabilization in the adult brain. It plays an essential role in breaking plasticity and maintaining connections between nerve cells in the developmental and adult brain.
Also, the researchers were able to show that blocking miR-29a in adult animals reverses the developmental downregulation of the miR-29. A target and induces a form of ocular plasticity with typical physiological and molecular features of plasticity at sensitive stages.
In summary, data published in the journal EMBO Reports indicate that miR-29a is an essential modulator of plastic breakdown, promoting age-related stabilization of visual cortical connections. The observation that miR29a is a remodeler of mature neural networks opens up a new and promising therapeutic perspective. miR-29a and other miR-29 family members, promoting brain plasticity during aging and regeneration of brain damage.
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