Cerebellar Contributions to Hypokinetic Symptoms in an Acute Lesion Parkinsonism Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. Rats and Experimental Groups
2.2. Electrodes
- Recording electrodes consisted of a stainless-steel monopolar bar (diameter: 250 μm, impedance: 3 MΩ) with a length adjusted to the target structure. The electrodes were soldered to male D-Sub crimp pins and insulated with resin, exposing 1 mm of the tip.
- Reference electrodes consisted of a No. 7 steel screw, 70%-covered with a copper wire (leaving the upper part of the screw exposed). The screw was connected to a male D-Sub crimp pin, with both joints soldered together. It was placed arbitrarily to avoid interference with the recording electrodes.
2.3. Surgical Procedures
2.4. Associated Behaviors
- Resting: A basal state of inactivity in which the rat maintains a static and relaxed position without exhibiting voluntary or exploratory movements, indicating a low level of motor activation.
- Grooming: Self-care and hygiene behavior during which the rat uses its limbs, mouth, and tongue to clean and groom different body areas, such as the face, ears, limbs, and fur. This process may also have been associated with emotional state and stress levels.
- Locomotion (walking): Active horizontal movement involving the voluntary displacement of the rat through the environment. This behavior is characterized by the coordinated use of all four limbs without adopting upright postures or significant changes in body orientation.
- Rearing: Active vertical exploratory behavior in which the rat elevates itself by supporting its hind limbs, typically extending the forelimbs to examine the surroundings. This behavior is indicative of active environmental stimulus search and spatial evaluation.
- Sniffing: An exploratory action focused on the sense of smell when resting. The rat performs nasal movements to capture and analyze chemical stimuli in the environment, facilitating food identification, social signal detection, and threat assessment.
2.5. Collection of Data
2.5.1. Electrophysiological Recording
2.5.2. Behavioral Recording
2.6. Electrophysiological Analysis and Power Spectral Density
Spectral Analysis
- Area under the curve (AUC) calculation per frequency band:
- 2.
- Normalization by bandwidth:
2.7. Statistical Analysis
- Intergroup comparisons: The Mann–Whitney U test was applied for each measurement week to compare the control and experimental groups. This test was used to identify significant differences in each behavior between the two groups.
- Intragroup comparisons: The Friedman test was employed to evaluate global differences across the different measurement periods within each group. In cases where the Friedman test was significant, post hoc analyses were performed using the Wilcoxon tests with Holm adjustment to identify specific differences between weeks.
- Correlation analysis: A correlation analysis was conducted to explore the relationship between time and normalized PSD values. For this, a Spearman correlation test was used. This analysis was performed independently of brain structure and measurement week.
3. Results
3.1. Intergroup Comparison
- Grooming: W1 (U = 96.0, p = 0.0051), W2 (U = 86.0, p = 0.0021);
- Locomotion: W1 (U = 100.0, p = 0.0071), W2 (U = 73.0, p = 0.0006);
- Rearing: W1 (U = 117.0, p = 0.0256), W2 (U = 119.0, p = 0.0294).
- Grooming: (U = 49.0, p < 0.0001);
- Locomotion: (U = 75.5, p = 0.0008);
- Sniffing: (U = 99.0, p = 0.0066).
3.2. Intragroup Comparison
- Resting: W3 and W4 showed a decrease compared to W2.
- Grooming: W3 and W4 showed a decrease compared to W1, while in W3, this decrease was also observed compared to W2, and in W4, it showed an increase compared to W3.
- Locomotion: a decrease was observed in W2, W3, and W4 compared to W1.
- Rearing: W2, W3, and W4 showed a significant decrease compared to W1, a decrease in W3 and W4 compared to W2 was also observed, and W4 showed an increase compared to W3.
- Resting: W4 represented a decrease compared to W3.
- Grooming: W4 exhibited a significant decrease compared to W1, W2, and W3.
- Locomotion and rearing: a decreasing pattern was observed in W4, but only compared to W1 and W2, with no differences in the remaining weeks.
- Sniffing: W4 decreased compared to W1, W2, and W3, respectively.
- Resting: there was a decrease only in W4 compared to W3.
- Grooming, locomotion, and sniffing: W4 exhibited a significant decrease compared to W2.
3.3. Behavioral Analysis
3.4. Correlation Analysis
4. Discussion
5. Perspectives and Limitations
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AP | Anteroposterior |
AUC | Area Under the Curve |
BG | Basal Ganglia |
DBS | Deep Brain Stimulation |
DN | Dentate Nucleus |
DV | Dorsoventral |
IO | Inferior Olive |
ML | Mediolateral |
MUA | Multiunit Activity |
PD | Parkinson’s Disease |
PSD | Power Spectral Density |
VLS | Ventrolateral Striatum |
Appendix A
Appendix A.1. Median Values of Normalized PSD and Behavior Execution Time
Structure | Behavior | Week | Control [fV2/Hz] | Experimental [fV2/Hz] | ||||
---|---|---|---|---|---|---|---|---|
Median | Q1 | Q3 | Median | Q1 | Q3 | |||
Crus II | Resting | 1 | 0.0460 | 0.0079 | 0.1452 | 0.0543 | 0.0158 | 0.3390 |
2 | 0.0187 | 0.0111 | 0.0579 | 0.0895 | 0.0195 | 0.2038 | ||
3 | 0.0463 | 0.0159 | 0.1181 | 0.0775 | 0.0025 | 0.1758 | ||
4 | 0.0241 | 0.0165 | 0.0569 | 0.0696 | 0.0081 | 0.1704 | ||
Grooming | 1 | 0.1062 | 0.0245 | 0.2015 | 0.4488 | 0.0568 | 0.5124 | |
2 | 0.0399 | 0.0231 | 0.1105 | 0.1817 | 0.0533 | 0.3471 | ||
3 | 0.0572 | 0.0371 | 0.2513 | 0.1072 | 0.0100 | 0.2297 | ||
4 | 0.0304 | 0.0236 | 0.1269 | 0.1352 | 0.0247 | 0.3144 | ||
Locomotion | 1 | 0.0844 | 0.0258 | 0.2938 | 0.5793 | 0.0738 | 0.7022 | |
2 | 0.0136 | 0.0093 | 0.0901 | 0.2016 | 0.0404 | 0.4122 | ||
3 | 0.0870 | 0.0394 | 0.3372 | 0.1269 | 0.0112 | 0.4024 | ||
4 | 0.0437 | 0.0356 | 0.1270 | 0.1301 | 0.0204 | 0.3227 | ||
Rearing | 1 | 0.1192 | 0.0482 | 0.7493 | 0.8787 | 0.1040 | 0.9025 | |
2 | 0.0455 | 0.0223 | 0.5684 | 0.3583 | 0.0314 | 0.6795 | ||
3 | 0.0926 | 0.0389 | 0.8566 | 0.1967 | 0.0132 | 0.4365 | ||
4 | 0.0864 | 0.0456 | 0.3204 | 0.2417 | 0.0197 | 0.5270 | ||
Sniffing | 1 | 0.0907 | 0.0206 | 0.1563 | 0.1171 | 0.0321 | 0.3034 | |
2 | 0.0163 | 0.0117 | 0.0611 | 0.1168 | 0.0448 | 0.2793 | ||
3 | 0.0478 | 0.0183 | 0.1281 | 0.0730 | 0.0020 | 0.2184 | ||
4 | 0.0289 | 0.0182 | 0.0533 | 0.0831 | 0.0115 | 0.2468 |
Structure | Behavior | Week | Control [fV2/Hz] | Experimental [fV2/Hz] | ||||
---|---|---|---|---|---|---|---|---|
Median | Q1 | Q3 | Median | Q1 | Q3 | |||
Inferior olive | Resting | 1 | 0.00969 | 0.00404 | 0.0382 | 0.026 | 0.01 | 0.0687 |
2 | 0.0218 | 0.0088 | 0.0522 | 0.00969 | 0.0084 | 0.0694 | ||
3 | 0.0115 | 0.00908 | 0.0307 | 0.0564 | 0.0117 | 0.14166 | ||
4 | 0.012 | 0.00478 | 0.029 | 0.0117 | 0.00264 | 0.05 | ||
Grooming | 1 | 0.0685 | 0.0177 | 0.18222 | 0.164119 | 0.0493 | 0.241812 | |
2 | 0.0246 | 0.0203 | 0.135983 | 0.0717 | 0.0438 | 0.197312 | ||
3 | 0.0758 | 0.0412 | 0.116298 | 0.0473 | 0.0242 | 0.205878 | ||
4 | 0.0588 | 0.0207 | 0.0888 | 0.0293 | 0.0137 | 0.0469 | ||
Locomotion | 1 | 0.0355 | 0.0124 | 0.0821 | 0.0912 | 0.0343 | 0.170791 | |
2 | 0.0649 | 0.0082 | 0.139841 | 0.0464 | 0.0194 | 0.16514 | ||
3 | 0.0334 | 0.0259 | 0.0544 | 0.0271 | 0.00386 | 0.190242 | ||
4 | 0.0365 | 0.013 | 0.0973 | 0.0159 | 0.00768 | 0.0398 | ||
Rearing | 1 | 0.0591 | 0.0229 | 0.151807 | 0.129852 | 0.018 | 0.282026 | |
2 | 0.0767 | 0.0199 | 0.174694 | 0.0775 | 0.0176 | 0.275724 | ||
3 | 0.0593 | 0.0327 | 0.11991 | 0.0491 | 0.00321 | 0.404475 | ||
4 | 0.0435 | 0.0248 | 0.102217 | 0.0211 | 0.00745 | 0.0644 | ||
Sniffing | 1 | 0.0193 | 0.0123 | 0.0482 | 0.0865 | 0.0156 | 0.146023 | |
2 | 0.0162 | 0.00815 | 0.0379 | 0.0382 | 0.0151 | 0.160667 | ||
3 | 0.0206 | 0.011 | 0.0409 | 0.0468 | 0.00948 | 0.159506 | ||
4 | 0.0203 | 0.00933 | 0.0486 | 0.0145 | 0.00375 | 0.0417 |
Structure | Behavior | Week | Control [fV2/Hz] | Experimental [fV2/Hz] | ||||
---|---|---|---|---|---|---|---|---|
Median | Q1 | Q3 | Median | Q1 | Q3 | |||
Dentate nucleus | Resting | 1 | 0.00636 | 0.00394 | 0.0189 | 0.00691 | 0.00584 | 0.021 |
2 | 0.007 | 0.00506 | 0.0119 | 0.0117 | 0.00544 | 0.0698 | ||
3 | 0.00642 | 0.00334 | 0.0192 | 0.00934 | 0.0022 | 0.0507 | ||
4 | 0.00479 | 0.00319 | 0.00528 | 0.00615 | 0.00167 | 0.0226 | ||
Grooming | 1 | 0.0219 | 0.0169 | 0.0319 | 0.0238 | 0.0115 | 0.139797 | |
2 | 0.0209 | 0.014 | 0.029 | 0.0825 | 0.0341 | 0.14262 | ||
3 | 0.0354 | 0.0285 | 0.0447 | 0.0296 | 0.00697 | 0.0554 | ||
4 | 0.00964 | 0.00741 | 0.0179 | 0.0217 | 0.00805 | 0.0407 | ||
Locomotion | 1 | 0.01 | 0.0086 | 0.0224 | 0.0123 | 0.00832 | 0.0485 | |
2 | 0.00866 | 0.00701 | 0.0106 | 0.0469 | 0.0126 | 0.123047 | ||
3 | 0.0219 | 0.0102 | 0.0317 | 0.0155 | 0.00246 | 0.0544 | ||
4 | 0.00602 | 0.00484 | 0.0158 | 0.0246 | 0.00516 | 0.0322 | ||
Rearing | 1 | 0.0177 | 0.0129 | 0.0231 | 0.0164 | 0.0136 | 0.0823 | |
2 | 0.0175 | 0.0134 | 0.0198 | 0.0681 | 0.0104 | 0.13338 | ||
3 | 0.0294 | 0.0204 | 0.0326 | 0.02 | 0.00276 | 0.0952 | ||
4 | 0.00811 | 0.00538 | 0.0288 | 0.0163 | 0.00377 | 0.0638 | ||
Sniffing | 1 | 0.018 | 0.00971 | 0.0262 | 0.012 | 0.00914 | 0.0667 | |
2 | 0.00878 | 0.00669 | 0.0113 | 0.0214 | 0.00944 | 0.0668 | ||
3 | 0.0153 | 0.00733 | 0.0182 | 0.0126 | 0.00177 | 0.0472 | ||
4 | 0.00657 | 0.00387 | 0.0116 | 0.00616 | 0.00232 | 0.0257 |
Behavior | Week | Control [s] | Experimental [s] | ||||
---|---|---|---|---|---|---|---|
Median | Q1 | Q3 | Median | Q1 | Q3 | ||
Resting | 1 | 141.15 | 122.23 | 157.90 | 352.80 | 221.68 | 488.50 |
2 | 370.70 | 285.76 | 383.15 | 356.95 | 309.80 | 417.40 | |
3 | 377.05 | 285.35 | 384.26 | 273.55 | 219.68 | 338.51 | |
4 | 334.92 | 253.10 | 404.83 | 387.70 | 305.84 | 437.00 | |
Grooming | 1 | 80.53 | 47.45 | 144.60 | 43.23 | 0.00 | 59.00 |
2 | 94.25 | 9.00 | 127.95 | 71.00 | 18.90 | 177.85 | |
3 | 55.72 | 49.15 | 77.73 | 81.10 | 65.25 | 97.88 | |
4 | 86.98 | 38.54 | 132.46 | 66.80 | 45.69 | 96.45 | |
Locomotion | 1 | 44.70 | 40.41 | 85.04 | 62.60 | 10.60 | 78.05 |
2 | 30.00 | 22.96 | 40.46 | 25.70 | 14.23 | 40.05 | |
3 | 52.55 | 39.39 | 60.55 | 18.58 | 8.59 | 27.45 | |
4 | 38.40 | 18.70 | 40.60 | 48.60 | 0.00 | 72.00 | |
Rearing | 1 | 75.30 | 43.70 | 109.53 | 19.65 | 3.20 | 26.11 |
2 | 25.43 | 9.53 | 40.73 | 3.70 | 2.55 | 18.40 | |
3 | 27.30 | 27.30 | 40.60 | 45.25 | 11.63 | 56.64 | |
4 | 20.90 | 20.45 | 51.40 | 15.40 | 3.30 | 24.55 | |
Sniffing | 1 | 88.05 | 65.43 | 194.66 | 33.20 | 25.54 | 53.95 |
2 | 87.25 | 56.30 | 102.50 | 43.50 | 34.60 | 138.31 | |
3 | 76.63 | 52.05 | 82.60 | 93.25 | 68.60 | 124.55 | |
4 | 88.95 | 87.00 | 104.30 | 75.90 | 16.00 | 114.56 |
Appendix A.2. PSD Statistical Test Values for Intragroup Comparison
Structure | Behavior | Friedman Statistical Value | Wilcoxon Statistical Value by Weeks Compared | |||||
---|---|---|---|---|---|---|---|---|
(1, 2) | (1, 3) | (1, 4) | (2, 3) | (2, 4) | (3, 4) | |||
Crus II | Resting | 18.78 | 87 | 56 | 56 | 21 | 16 | 102 |
Grooming | 48.48 | 28 | 0 | 10 | 0 | 37 | 0 | |
Locomotion | 29.70 | 16 | 0 | 4.5 | 54 | 50 | 92 | |
Rearing | 54.18 | 1 | 0 | 0 | 0 | 11 | 18 | |
Sniffing | 15.18 | 102 | 50 | 64 | 56 | 65 | 57 |
Structure | Behavior | Friedman p-Value | Wilcoxon p-Value by Weeks Compared | |||||
---|---|---|---|---|---|---|---|---|
(1, 2) | (1, 3) | (1, 4) | (2, 3) | (2, 4) | (3, 4) | |||
Crus II | Resting | 0.0003036 | 1.0 | 1.0 | 1.0 | 0.0280724 | 0.0116043 | 1.0 |
Grooming | 0.0000000 | 0.0840797 | 0.0000916 | 0.0031986 | 0.0000916 | 0.2641983 | 0.0000916 | |
Locomotion | 0.0000016 | 0.0116043 | 0.0000916 | 0.0007629 | 1.0 | 0.8797684 | 1.0 | |
Rearing | 0.0000000 | 0.0001564 | 0.0000916 | 0.0000916 | 0.0000916 | 0.0039864 | 0.0164070 | |
Sniffing | 0.0016691 | 1.0 | 0.8797684 | 1.0 | 1.0 | 1.0 | 1.0 |
Structure | Behavior | Friedman Statistical Value | Wilcoxon Statistical Value by Weeks Compared | |||||
---|---|---|---|---|---|---|---|---|
(1, 2) | (1, 3) | (1, 4) | (2, 3) | (2, 4) | (3, 4) | |||
Inferior olive | Resting | 21.30 | 93 | 43 | 88 | 43 | 48 | 23 |
Grooming | 42.54 | 92 | 52 | 0 | 19 | 0 | 0 | |
Locomotion | 27.42 | 93 | 75 | 5 | 54 | 0 | 57 | |
Rearing | 23.40 | 69 | 87 | 10 | 73 | 13 | 53 | |
Sniffing | 34.90 | 86 | 96 | 0 | 52 | 1 | 0 |
Structure | Behavior | Friedman p-Value | Wilcoxon p-Value by Weeks Compared | |||||
---|---|---|---|---|---|---|---|---|
(1, 2) | (1, 3) | (1, 4) | (2, 3) | (2, 4) | (3, 4) | |||
Inferior olive | Resting | 0.0000912 | 1.0 | 0.4423752 | 1.0 | 0.4423752 | 0.6553650 | 0.0302315 |
Grooming | 0.0000000 | 1.0 | 0.9203777 | 0.0000687 | 0.0152245 | 0.0000687 | 0.0000687 | |
Locomotion | 0.0000048 | 1.0 | 1.0 | 0.0005531 | 0.9903870 | 0.0000687 | 1.0 | |
Rearing | 0.0000333 | 1.0 | 1.0 | 0.0022964 | 1.0 | 0.0045319 | 0.9570465 | |
Sniffing | 0.0000001 | 1.0 | 1.0 | 0.0000687 | 1.0 | 0.0001144 | 0.0000687 |
Structure | Behavior | Friedman Statistical Value | Wilcoxon Statistical Value by Weeks Compared | |||||
---|---|---|---|---|---|---|---|---|
(1, 2) | (1, 3) | (1, 4) | (2, 3) | (2, 4) | (3, 4) | |||
Dentate nucleus | Resting | 12.12 | 59 | 65 | 72 | 87 | 42 | 9 |
Grooming | 22.02 | 60 | 104 | 54.5 | 25 | 0 | 35 | |
Locomotion | 13.14 | 56 | 93 | 97 | 49 | 17 | 81 | |
Rearing | 12.78 | 51 | 60 | 96 | 70 | 31 | 87 | |
Sniffing | 20.22 | 62 | 83 | 36 | 52 | 0 | 51 |
Structure | Behavior | Friedman p-Value | Wilcoxon p-Value by Weeks Compared | |||||
---|---|---|---|---|---|---|---|---|
(1, 2) | (1, 3) | (1, 4) | (2, 3) | (2, 4) | (3, 4) | |||
Dentate nucleus | Resting | 0.0069832 | 1.0 | 1.0 | 1.0 | 1.0 | 0.5841675 | 0.0032101 |
Grooming | 0.0000646 | 1.0 | 1.0 | 1.0 | 0.0692863 | 0.0001030 | 0.2626419 | |
Locomotion | 0.0043434 | 1.0 | 1.0 | 1.0 | 1.0 | 0.0185566 | 1.0 | |
Rearing | 0.0051373 | 1.0 | 1.0 | 1.0 | 1.0 | 0.1603966 | 1.0 | |
Sniffing | 0.0001528 | 1.0 | 1.0 | 0.2907944 | 1.0 | 0.0001030 | 1.0 |
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Structure | AP [mm] | ML [mm] | DV [mm] |
---|---|---|---|
VLS | −0.48 | ±4.40 | −6.80 |
Crus II | −14.00 | 3.40 | −5.00 |
IO | −11.80 | 0.80 | −11.00 |
DN | −11.30 | 3.40 | −6.40 |
Behavior | Structure | ||
---|---|---|---|
Crus II | IO | DN | |
Resting | −0.038235294 | −0.05 | −0.241176471 |
Grooming | −0.6136867 | −0.566593237 | −0.644591786 |
Locomotion | 0.380532629 | 0.286136938 | 0.333334784 |
Rearing | 0.085546095 | 0.209440439 | 0.292036669 |
Sniffing | 0.579411765 | 0.658823529 | 0.579411765 |
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Zarate-Calderon, C.; Marín, G.; Viveros-Martínez, I.; Vásquez-Celaya, L.; Carrillo-Castilla, P.; Aranda-Abreu, G.E.; Chi-Castañeda, D.; García, L.I. Cerebellar Contributions to Hypokinetic Symptoms in an Acute Lesion Parkinsonism Model. Neurol. Int. 2025, 17, 72. https://doi.org/10.3390/neurolint17050072
Zarate-Calderon C, Marín G, Viveros-Martínez I, Vásquez-Celaya L, Carrillo-Castilla P, Aranda-Abreu GE, Chi-Castañeda D, García LI. Cerebellar Contributions to Hypokinetic Symptoms in an Acute Lesion Parkinsonism Model. Neurology International. 2025; 17(5):72. https://doi.org/10.3390/neurolint17050072
Chicago/Turabian StyleZarate-Calderon, Cristofer, Gerardo Marín, Iraís Viveros-Martínez, Lizbeth Vásquez-Celaya, Porfirio Carrillo-Castilla, Gonzalo E. Aranda-Abreu, Donaji Chi-Castañeda, and Luis I. García. 2025. "Cerebellar Contributions to Hypokinetic Symptoms in an Acute Lesion Parkinsonism Model" Neurology International 17, no. 5: 72. https://doi.org/10.3390/neurolint17050072
APA StyleZarate-Calderon, C., Marín, G., Viveros-Martínez, I., Vásquez-Celaya, L., Carrillo-Castilla, P., Aranda-Abreu, G. E., Chi-Castañeda, D., & García, L. I. (2025). Cerebellar Contributions to Hypokinetic Symptoms in an Acute Lesion Parkinsonism Model. Neurology International, 17(5), 72. https://doi.org/10.3390/neurolint17050072