Figure 3. Chlorzoxazone-baclofen improves Atxn1^154Q/2Q Purkinje neuron physiology in a dose-responsive manner.

Acute cerebellar slices were prepared from 14 week-old Atxn1^154Q/2Q mice for all recordings. (A) Regularity of Purkinje neuron spiking was recorded by measuring the coefficient of variation (CV) of the interspike interval (ISI). CV of the ISI was recorded at baseline and normalized to 1.0, and was then recorded after perfusion of differing concentrations of chlorzoxazone and baclofen into the bath. Dotted line represents normalized CV of the ISI from age-matched wild-type littermate controls. (B) Firing frequency was recorded at baseline and normalized to 1.0, and was then recorded after perfusion of differing concentrations of chlorzoxazone and baclofen into the bath. Dotted line represents normalized baseline firing frequency from age-matched wild-type littermate controls. (C) Similar to (A), CV of the ISI was recorded at baseline and after perfusion of an intermediate dose of chlorzoxazone (10 µM). Dotted line represents normalized CV of the ISI from age-matched wild-type littermate controls. (D) Similar to (C), CV of the ISI was recorded at baseline and after perfusion an intermediate dose of baclofen (400 nM). Dotted line represents normalized CV of the ISI from age-matched wild-type littermate controls. * denotes p<0.05; ** denotes p<0.01; *** denotes p<0.001; ns denotes p>0.05. Paired Student’s t-test.