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• W2529632021 abstract "People with Rett syndrome (RTT) have defects in motor function also seen in Mecp2 ‐null mice. Motor function depends on not only central motor commands but also sensory feedback that is vulnerable to changes in excitability of propriosensory neurons. Here we report evidence for hyperexcitability of mesencephalic trigeminal (Me5) neurons in Mecp2 ‐null mice and a novel cellular mechanism for lowering its impact. In in vitro brain slices, the Me5 neurons in both Mecp2 −/Y male and symptomatic Mecp2 +/− female mice were overly excitable showing increased firing activity in comparison to their wild‐type (WT) male and asymptomatic counterparts. In Mecp2 −/Y males, Me5 neurons showed a reduced firing threshold. Consistently, the steady‐state activation of voltage‐gated Na + currents (I Na ) displayed a hyperpolarizing shift in the Mecp2 ‐null neurons with no change in the I Na density. This seems to be due to NaV1.1, SCN1B and SCN4B overexpression and NaV1.2 and SCN3B under‐expression. In contrast to the hyperexcitability, the sag potential and postinhibitory rebound (PIR) were reduced in Mecp2 ‐null mice. In voltage‐clamp, the I H density was deficient by ∼33%, and the steady‐state half‐activation had a depolarizing shift of ∼10 mV in the Mecp2 ‐null mice. Quantitative PCR analysis indicated that HCN2 was decreased, HCN1 was upregulated with no change in HCN4 in Mecp2 −/Y mice compared to WT. Lastly, blocking I H reduced the firing rate much more in WT than in Mecp2 ‐null neurons. These data suggest that the Mecp2 defect causes an increase in Me5 neuronal excitability likely attributable to alterations in I Na , meanwhile I H is reduced likely altering neuronal excitability as well. J. Cell. Physiol. 232: 1151–1164, 2017. © 2016 Wiley Periodicals, Inc." @default.
• W2529632021 created "2016-10-14" @default.
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• W2529632021 date "2016-09-30" @default.
• W2529632021 modified "2023-10-17" @default.
• W2529632021 title "Hyperexcitability of Mesencephalic Trigeminal Neurons and Reorganization of Ion Channel Expression in a Rett Syndrome Model" @default.
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• W2529632021 doi "https://doi.org/10.1002/jcp.25589" @default.
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• W2529632021 hasPublicationYear "2016" @default.
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