Pharmacological DNA Demethylation Weakens Inhibitory Synapses in the Auditory Cortex and Re-opens the Critical Period for Frequency Map Plasticity. (1st August 2020)

• Record Type: Journal Article
• Authors: Schwartz, Benjamin A.; Wang, Weihua; Bao, Shaowen
• Is Part Of: Neuroscience. Volume 440(2020)
• Page Start: 239
• Page End: 248
• Publication Date: 2020-08-01
• Subjects: aCSF artificial cerebrospinal fluid -- AI auditory cortex -- CF characteristic frequency -- CP critical period -- DNA-ME DNA methylation -- LSD least significant difference -- mIPSCs miniature inhibitory postsynaptic currents; epigenetics -- critical period -- DNA methylation -- plasticity; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2020.05.056
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Primary auditory cortex accumulates DNA methylation as the critical period progresses into adulthood. DNA demethylation in adult mice re-established critical period-like frequency map plasticity. DNA demethylation in adult mice shifted features such as response latencies and mIPSC frequency to critical period levels. DNA demethylation in adult mice reversed the expression of BDNF and REST back to critical period levels. Abstract: The critical period is a time of maximal plasticity within the cortex. The progression of the critical period is marked by experience-dependent transcriptional alterations in cortical neurons, which in turn shifts the excitatory-inhibitory balance in the brain, and accordingly reduces plasticity. Epigenetic mechanisms, such as DNA methylation, control the transcriptional state of neurons, and have been shown to be dynamically regulated during the critical period. Here we show that adult animals have a significantly higher concentration of DNA methylation than critical period animals. Pharmacological reduction of DNA methylation in adult animals re-establishes critical period auditory map plasticity. Furthermore, the reduction of DNA methylation in adult animals, reverted intrinsic characteristics of inhibitory synapses to an immature state. Our data suggest that accumulation of DNA methylation during the critical period confers a mature phenotype to cortical neurons, which in turn, facilitates the reduction in plasticity seen after the critical period.