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• W4387307611 abstract "Abstract Rett Syndrome (RTT) is a severe neurodevelopmental disorder that mainly affects girls and women due to silencing mutations in the X-linked MECP2 gene. One of the most troubling symptoms of RTT is breathing irregularity, including apneas, breath-holds, and hyperventilation. Mice with silencing mutations in Mecp2 exhibit breathing abnormalities similar to human patients and serve as useful models for studying mechanisms underlying breathing problems in RTT. Previous work implicated the pontine, respiratory-controlling Kölliker-Fuse (KF) in the breathing problems in RTT. The goal of this study was to test the hypothesis that inhibitory synaptic transmission is deficient in KF neurons from symptomatic male and female RTT mice. We performed whole-cell voltage-clamp recordings from KF neurons in acute brain slices to examine pharmacologically isolated, spontaneous and electrically evoked inhibitory post-synaptic currents (IPSCs) in RTT mice and age- and sex-matched wild type mice. The frequency of spontaneous IPSCs was reduced in KF neurons from male RTT mice, but not female RTT mice. In addition, electrically evoked IPSCs were less reliable in KF neurons from male RTT mice, but not female RTT mice. KF neurons from male RTT mice were also more excitable and exhibited shorter duration action potentials. Increased excitability of KF neurons from male mice was not explained by changes in axon initial segment length. These findings indicate impaired inhibitory neurotransmission and increased excitability of KF neurons in male, but not female RTT mice, and suggest that sex-dependent mechanisms contribute to breathing problems in RTT. New and Noteworthy Kölliker-Fuse (KF) neurons in acute brain slices from male Rett syndrome (RTT) mice receive reduced inhibitory synaptic inputs compared with wild type littermates. In female RTT mice, inhibitory transmission was not different in KF neurons compared with controls. The results from this study show that sex-specific alterations in synaptic transmission occur in the KF of RTT mice. Graphical Abstract" @default.
• W4387307611 created "2023-10-04" @default.
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• W4387307611 date "2023-10-02" @default.
• W4387307611 modified "2023-10-10" @default.
• W4387307611 title "Inhibitory synaptic transmission is impaired in the Kölliker-Fuse of male, but not female, Rett Syndrome Mice" @default.
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• W4387307611 doi "https://doi.org/10.1101/2023.10.02.560501" @default.
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