Article Figures & Data
Figures
- Figure 1.
Behavioral task in hemiparkinsonian rats. A, Schematic of the right–left pedal task (top) and a representative of the pedal trajectory during one correct trial in the right-rewarded block (middle and bottom). Rats push both pedals for at least 1 s and release only one limb (depending on which movement is being rewarded in that block) to receive a reward. B, Experiment design timeline. C, Representatives of task performance at day 2 (top) and day 14 (bottom). Large and small colored vertical bars (red, right choice; blue, left choice) indicate correct and incorrect trials, respectively. The choice rate of the right pedal (purple line) was calculated by averaging the number of right choices obtained from the past 10 trials. D, Representative images of M2, M1, DLS, and SNc showing TH immunostaining difference between the non-lesioned and lesioned hemisphere. E, TH staining optical density values of the lesioned hemisphere normalized to the non-lesioned hemisphere in M2, M1, and DLS (top); number of SNc TH+ cells in the non-lesioned (NL) and lesioned (L) hemisphere (bottom left); difference of total turns in 1 h after apomorphine injection between healthy and hemiparkinsonian rats (bottom right); **p < 0.01, n.s.: not significant, unpaired t test. F, Population averaged M1 LFP power spectra around the onset of contralateral pedal release (±1.5 s) showing the LFP power and peak frequency in the β range (15–35 Hz) in the lesioned hemisphere; **p < 0.01, Wilcoxon rank-sum test. G, Wavelet coherence between M1 and M2 LFP signals around the onset of contralateral pedal release. Coherence was normalized to fall between 0 and 1.
- Figure 2.
Task performance. A, top, Pedal trajectories of right and left forelimbs during task performance in hemiparkinsonian rat. Middle and bottom, Averaged population EMG activity (±SEM) of both forelimbs aligned to pedal-release onset, during right or left forelimb movements (left and right columns, respectively). B, EMG activity of left forelimb in healthy rat showing left muscles activity change associated with movement execution of the left forelimb. C, Rate of correct responses for each forelimb in hemiparkinsonian rat. In the first 4 d of training, the number of correct trials was higher for the right forelimb than the left forelimb; **p < 0.01, two-way ANOVA with Tukey–Kramer post hoc test. D, Correct rate after block change in hemiparkinsonian rat. Solid lines represent the number of trials needed to correctly change the response after a block change in training day 14. At the end of the training period, this number was similar for both forelimbs. The faint lines represent training day 6. E, The rat chooses the correct pedal based on the reward. Relative to healthy rats, lesioned rats exhibited a higher bias toward the right in the initial 4 d of training; **p < 0.01 compared to the corresponding day of healthy group, two-way ANOVA, Tukey–Kramer post hoc test. F, Rate of correct responses. The healthy rats showed a higher rate of correct responses during days 7–9, choosing the rewarded pedal >75% of the time; **p < 0.01 compared to the corresponding day of healthy group, two-way ANOVA with Tukey–Kramer post hoc test. G, Number of total trials per session.
- Figure 3.
Different types of functional activity neurons in M1 and M2. A, Spiking properties of RS and FS neurons of M1 and M2. Ongoing spike rate (left); CV of ISI, showing the cumulative distribution in the insets (middle); peak activity timing of preferred activity (right); n.s.: not significant, Kruskal–Wallis test (H, healthy; NL, non-lesioned hemisphere; L, lesioned hemisphere). B, Examples of neurons with different functional activities recorded from the lesioned hemisphere, showing the raster plot and PETH around the onset of pedal release for a Go-type and a Hold-type neuron during contralateral (red) and ipsilateral (blue) movements. C, D, Task-related activity in RS (top) and FS (bottom) neurons in M1 and M2. Color map shows the normalized Gaussian-filtered PETH of the preferred response (σ = 12.5 ms, in 0.05-ms bins) for a single neuron (aligned with pedal release onset). Task-related neurons were sorted by peak activity time (early to late). Hold-type (gray) and Go-type (white) activities are indicated on the right side of each panel. E, F, Proportion of Hold-type (black) and Go-type (white) for RS and FS neurons; **p < 0.01, n.s.: not significant, χ2 test.
- Figure 4.
Forelimb selectivity of neuronal activity. Go-type neurons activity during contralateral and ipsilateral movements in RS and FS neurons in M1 (A) and M2 (B). The plots show the averaged PETHs of all Go-type activity during contralateral (red) and ipsilateral (blue) choice trials. Solid lines represent means, shaded areas represent ±SD. H, healthy; L, lesioned; NL, non-lesioned. The insets show the difference between the average peak values during contralateral and ipsilateral movements. Wilcoxon rank-sum test.
- Figure 5.
Laterality preference of Go-type activity in unidentified neurons in M1 and M2. A, Cumulative distributions of laterality indices for RS and FS neurons in M1 and M2. A laterality index near +1 indicates preferred activity during contralateral movements, and an index near –1 indicates a preference for ipsilateral movements. Each line represents the lateralized activity of the indicated neuron population under healthy (gray), non-lesioned (cyan), and lesioned (magenta) conditions. B, Proportion of neurons (in percentage) selective for contralateral (red), ipsilateral (blue), or bilateral movement (green); **p < 0.01, n.s.: not significant, χ2 test.
- Figure 6.
Identification and laterality preference of IT and PT neurons. A, Schematic of the localization of recording probes and optical fiber for performance of Multi-Linc in M1 and M2 (contralateral cortex stimulation for the identification of IT neurons; ipsilateral pons stimulation for PT neurons). B, Example identification of a PT neuron using the collision test. Black traces represent antidromic spikes after optical stimulation (cyan area). Red traces show the absence of the antidromic spike after optical stimulation triggered by a spontaneous spike, confirming a successful collision test. C, Cumulative distributions of laterality indices for IT and PT neurons in M1 and M2. A laterality index near +1 indicates preferred activity during contralateral movements, and an index near –1 indicates a preference for ipsilateral movements. Each line indicates the lateralized activity of each neuron population under healthy (gray), non-lesioned (cyan), and lesioned (magenta) conditions. D, Proportion of neurons (in percentage) selective for contralateral (red), ipsilateral (blue), or bilateral movement (green); *p < 0.05, **p < 0.01, n.s.: not significant, χ2 test.
- Figure 7.
Disrupted lateralized activity of motor cortex. The present model represents the degree of ipsilateral or contralateral control depicted as the arrow thickness. A, Normal contralateral lateralized activity of motor cortex. B, Classic rate model of PD and hypothetical compensation from the contralateral hemisphere. C, Our results indicate a decrease in the contralateral preferred control in the dopamine-depleted hemisphere. The empty arrows represent a reduced action selectivity (e.g., flexion or extension) in the parkinsonian state. D, Projection neurons and putative interneurons on the lesioned side exhibited a reduction in contralateral preference which can coexist with a decrease in the action selectivity. The non-lesioned hemisphere exhibited an increased contralateral preference in FS neurons and a tendency toward an increase in the contralateral preference in projection neurons, acting as a possible compensatory mechanism, exerting a higher control over the abnormal activity of the dopamine depleted hemisphere.
In this issue
