Rescuing intrinsic dendritic excitability improves SCA1 mouse motor performance.

<p><b>(A)</b> Representative traces from Purkinje neurons at five weeks of age where dendritic calcium spikes were evoked with somatic current injection (injected current amount indicated on the trace). Recordings are from wild-type mice treated with GFP-AAV (left), ATXN1[82Q] mice treated with GFP-AAV (middle), and ATXN1[82Q] mice treated with BK-AAV and recorded in the presence of 2 μm baclofen (right). <b>(B)</b> At five weeks of age, Purkinje neurons from ATXN1[82Q] mice which had been injected with BK-AAV and recorded in the presence of 2 μm baclofen and 1 μM TTX show a normalization of their dendritic calcium spike threshold. Data are mean ± SEM. * = <i>P<0</i>.<i>05</i>. Statistical significance derived by one-way ANOVA with Holm-Sidak multiple comparison test with. N = 4–6 mice were utilized per group. <b>(C)</b> Input resistance is consistent across all conditions tested when measured in normal aCSF with 1 μm TTX. Data are mean ± SEM. * = <i>P<0</i>.<i>05</i>. Statistical significance derived by one-way ANOVA with Holm-Sidak multiple comparison test with. N = 4–6 mice were utilized per group. <b>(D)</b> Rotarod task performance was improved in ATXN1[82Q] mice injected with BK-AAV and treated with baclofen, when compared to ATXN1[82Q] mice that received sham surgery and were treated with vehicle. Wild-type mice that were treated with vehicle were used as a control. Data are mean ± SEM. * = statistically-significant difference from Wild-Type + Vehicle; #* = statistically-significant difference ATXN1[82Q] + Sham + Vehicle. Statistical significance derived by repeated-measures two-way ANOVA with Holm-Sidak multiple comparison test. <b>(E)</b> Rotarod task performance was not improved in ATXN1[82Q] mice treated with baclofen alone, when compared to ATXN1[82Q] mice that were treated with vehicle. Untreated wild-type mice were used as a control. Data are mean ± SEM. * = statistically-significant difference from ATXN1[82Q] + Vehicle and ATXN1[82Q] + Baclofen; NS = not significant.