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In vitro assays indicated that the gain-in-function in trkB.T1<jats:sup> \u2212\/\u2212<\/jats:sup> animals resulted specifically from an increased muscle contractility, and increased electrically evoked calcium release. In the trkB.T1 null muscle, we identified an increase in Akt activation in resting muscle as well as a significant increase in trkB.FL and Akt activation in response to contractile activity. 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