Long-term cortical plasticity following sensory deprivation is reduced in male Rett model mice

Abstract

Purpose/Aim Rett (RTT) syndrome, a neurodevelopmental disorder, results from loss-of-function mutations in methyl-CpG-binding protein 2. We studied activity-dependent plasticity induced by sensory deprivation via whisker trimming in early symptomatic male mutant mice to assess neural rewiring capability. Methods One whisker was trimmed for 0-14 days and intrinsic optical imaging of the transient reduction of brain blood oxygenation resulting from neural activation by 1 second of wiggling of the whisker stump was compared to that of an untrimmed control whisker. Results Cortical evoked responses to wiggling a non-trimmed whisker were constant for 14 days, reduced for a trimmed whisker by 49.0 ± 4.3% in wild type (n = 14) but by only 22.7 ± 4.6% in mutant (n = 18, p = 0.001). Conclusion As the reduction in neural activation following sensory deprivation in whisker barrel cortex is known to be dependent upon evoked and basal neural activity, impairment of cortical re-wiring following whisker trimming provides a paradigm suitable to explore mechanisms underlying deficiencies in the establishment and maintenance of synapses in RTT, which can be potentially targeted by therapeutics.