Intracerebellar microinjection of paxilline in WT mice reproduces the rhythmic firing of Purkinje cells and the ataxic behavior of BK^−/− mice.

<p>(<i>A</i>,<i>B</i>) Spontaneous firing of a Purkinje cell recorded in a WT mouse (<i>A</i>) and corresponding autocorrelogram (<i>B</i>). Note the absence of rhythmicity. (<i>C</i>,<i>D</i>) The same, following microinjection of paxilline. (<i>E–H</i>) Bar graphs of Purkinje cells simple spike rhythmicity (n = 13)(<i>E</i>) and frequency (n = 13)(<i>F</i>), Purkinje cells complex spike frequency (n = 8)(<i>G</i>) and subsequent pause duration (n = 8) (<i>H</i>) before and after paxilline injection and in BK^−/− (n = 48, value illustrated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007991#pone-0007991-g002" target="_blank">fig 2</a> and reproduced here for comparison purpose). Stars indicate significance as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007991#pone-0007991-g002" target="_blank">fig 2</a>, for student t test for paired values (comparison between before and after injection) and unpaired values (comparison between WT PC after injection and PC in BK^−/−) (<i>I</i>,<i>J</i>) Runway test, bar graph of mean number of slips (<i>I</i>) and time to reach the end of the bar (<i>J</i>) before and after paxilline injection (n = 9).</p

Cerebellar cortices of BK^−/− mice present a LFPO in the beta-range phase-locked with both the simple and complex spikes.

<p>(<i>A–B</i>) Simultaneous recording of a LFPO and a Purkinje cell (250 µm-apart along the parallel fiber axis) and Fast-Fourier-Transform of the LFPO. (<i>C–F</i>). Spike-trigger averaging of the LFPO using the complex (C–D) and the simple (E–F) spike. Note the phase-difference in the phase-locking of complex and simple spikes. The smoother aspect of the simple spike triggered wave is due to the much greater number of triggering spikes. Traces D and F are low-pass filtered (<500 Hz); note the difference in time scale. Arrows indicate the time lag. (<i>G</i>) Simple spike autocorrelogram of the Purkinje cell illustrated in A. Arrow indicates the correspondence between low frequency rhythmicity and LFPO wave. (<i>H</i>) Cross-correlation function between the non-filtered simple and complex spike triggered averaging, confirming the time lag around 7 ms.</p

LFPO in BK^−/− mice is highly synchronized along the frontal and sagittal plane.

<p>(<i>A–B</i>) Simultaneous recordings of two LFPO with electrodes at a distance of 400 µm apart along the frontal (A) and sagittal (B) planes. (<i>C–D</i>) Cross-correlation function (CCF) of the recorded signals illustrated in A and B. (<i>E–F</i>) Plotted values of the maximal CCF coefficient and the corresponding distance between recording electrodes in a same BK^−/− mouse in the frontal (E) and in the sagittal (F) plane. Note the absence of significant variation.</p

Simple spike response of Purkinje cells to tactile stimulation is altered in BK^−/− mice.

<p>(<i>A</i>) Purkinje cells recorded in the Crus2A of a WT mouse during the stimulation of the whisker region, timing of stimulation is illustrated in the lower trace (CS = complex spike, SS = simple spike). (<i>B</i>,<i>C</i>) Bar graphs of complex (B) and simple (C) spike firing, 15 trials summed. (<i>D</i>) Purkinje cells recorded in the Crus2A of a BK^−/− mouse during the stimulation of the whisker region. (<i>E</i>,<i>F</i>) Bar graph of complex (E) and simple (F) spike firing, 26 trials summed. (<i>G</i>) Bar graph of timing between stimulus and complex spike firing in WT and BK^−/− mice. (<i>H</i>) Bar graph of simple spike response duration in WT and BK^−/− mice.</p

Clinical features of the DMD patients ordered by increasing age.

<p>Clinical features of the DMD patients ordered by increasing age.</p

Patient flow-chart.

<p>Patient flow-chart.</p

Reliability between test and retest for all the tasks evaluated for each ActiMyo^® variable.

<p><b>◇</b> MoviPlate; <b>⬜</b> BBT; <b>△</b> Minnesota test; <b>✱</b> Writing;<b>×</b> PC typing.</p

The tools.

<p><b>(A)</b> First version of ActiMyo^®, used in the current study. <b>(B)</b> Box and Block test. <b>(C)</b> Minnesota test with five discs.</p

The maximal scores on tasks completed by each patient at the two visits sorted by the decreasing age.

<p>The maximal scores on tasks completed by each patient at the two visits sorted by the decreasing age.</p

Correlation between the ActiMyo^® variables and the functional scores.

<p>Correlation between the ActiMyo^® variables and the functional scores.</p