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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳玉威 | zh_TW |
| dc.contributor.advisor | Yu-Wei Wu | en |
| dc.contributor.author | 胡昱庭 | zh_TW |
| dc.contributor.author | Yu-Ting Hu | en |
| dc.date.accessioned | 2025-09-24T16:43:41Z | - |
| dc.date.available | 2025-09-25 | - |
| dc.date.copyright | 2025-09-24 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-08-13 | - |
| dc.identifier.citation | 1 Horn, A. The Hidden Life of the Basal Ganglia: At the Base of Brain and Mind. Brain 144, doi:10.1093/brain/awab393 (2021).
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A.-O. & Jones, J. A. Propagation of Oscillations in the Indirect Pathway of the Basal Ganglia. (2023 ). 58 Ponzi, A. & Wickens, J. Sequentially switching cell assemblies in random inhibitory networks of spiking neurons in the striatum. 59 Mahringer, D., Zmarz, P., Okuno, H., Bito, H. & Keller, G. Functional correlates of immediate early gene expression in mouse visual cortex. (2020). | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/100170 | - |
| dc.description.abstract | 腦深層電刺激（DBS）通過電極在大腦深部的視丘下核（STN）施加高頻電刺激緩解帕金森氏症引起的運動症狀。儘管 STN-DBS 的療效仰賴對運動皮質（MO）投射至 STN 的調節，但 MO 在 DBS 過程中的實際角色仍未完全釐清。
本研究探討不同 DBS 頻率對 MO 神經動態的影響，以深入了解其治療機制。我們利用光遺傳技術選擇性地活化皮質投射至 STN 的路徑，並在半側帕金森氏症小鼠中進行活體雙光子鈣成像。雖然在多種頻率下小鼠的移動表現皆有所改善，但 MO 神經群體的反應則呈現頻率依賴性。值得注意的是，僅有高頻刺激能較好的維持與動作相關的皮質活動模式。另外，我們也發現第五層（L5）神經元與第二/三層（L2/3）神經元對刺激頻率的反應不同，暗示不同皮質層在電刺激下有各自的功能貢獻。 本研究結果強調調整 DBS 參數以保留內源性運動訊號之重要性，並為發展更精準的帕金森氏症神經調控療法提供了新的見解。 | zh_TW |
| dc.description.abstract | Deep brain stimulation (DBS) of the subthalamic nucleus (STN) provides effective relief of motor symptoms in Parkinson’s disease (PD). Although the therapeutic benefits of STN-DBS depend in part on modulating the motor cortical (MO) inputs to the STN, the precise role of MO during STN-DBS is not fully understood. Here, we examined how MO neuronal dynamics are influenced by different DBS frequencies to gain insights into therapeutic mechanisms and optimize neuromodulatory strategies.
We used optogenetic stimulation to selectively activate cortical projections to the STN while performing in vivo two-photon calcium imaging of motor cortex neurons in hemi-parkinsonian mice. Locomotor performance improved over a broad range of stimulation frequencies, yet the underlying MO population responses varied depending on the frequency. Layer-specific analyses revealed that layer 5 (L5) neurons, whose activity is attenuated in the Parkinsonian state, were robustly and consistently modulated across the tested frequencies. In contrast, layer 2/3 (L2/3) neurons were more sensitive to stimulation frequency, suggesting distinct circuit-level contributions. These findings highlight the importance of tailoring DBS parameters to preserve endogenous motor signals in the cortex while maximizing therapeutic effects. Our results provide insight into how frequency-dependent cortical dynamics under STN-DBS contribute to motor recovery, with implications for developing more precise neuromodulatory interventions for Parkinson’s disease. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-09-24T16:43:41Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-09-24T16:43:41Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 謝辭 i
中文摘要 iii ABSTRACT iv CONTENTS v LIST OF FIGURES ix ABBREVIATION LIST xi Chapter 1 Introduction 1 1.1 The cortico–basal ganglia–thalamic circuit and Parkinson’s disease 1 1.2 Subthalamic deep brain stimulation as a therapeutic Intervention 2 1.3 Mechanistic insights and limitations of previous STN-DBS studies 3 1.4 Research questions and experimental approach 5 Chapter 2 Methods 7 2.1 Animals 7 2.2 Stereotaxic surgeries 7 2.2.1 6-OHDA induced hemi-PD model 7 2.2.2 Optic fiber implantation 7 2.2.3 Cranial window surgery 8 2.3 Open field test 8 2.3.1 Experimental setup 8 2.3.2 Speed analysis 8 2.3.3 Rotational bias analysis 9 2.4 In vivo two-photon imaging 10 2.4.1 Two-photon microscopy setup 10 2.4.2 Imaging processing for identifying in vivo Ca2+ signal 10 2.5 Calcium imaging data preprocessing 11 2.5.1 Imaging trace processing 11 2.5.2 Fluorescence normalization 12 2.5.3 Calcium event detection 12 2.6 Calcium imaging data postprocessing 13 2.6.1 Antidromic analysis 13 2.7 Behavior data on the running wheel 14 2.7.1 Behavioral motion signal preprocessing 14 2.7.2 Running episodes detection 15 2.7.3 Motion-related event mask 15 Chapter 3 Results 16 3.1 Motor deficit in 6-OHDA induced hemi-Parkinson’s mice 16 3.2 In-vivo calcium signal recording at M1 from behaving mice 17 3.3 Motor deficit in 6-OHDA induced hemi-PD mice on the running wheel 17 3.4 Diminished neural engagement during movement in hemi-PD mice 18 3.5 Diminished neural correlation to movement in PD mice 20 3.6 Hyperdirect pathway specific opto-DBS restore mice locomotion in open field 21 3.7 Hyperdirect pathway specific opto-DBS restore mice locomotion on running wheel 22 3.8 Hyperdirect pathway specific opto-DBS increase healthy mice locomotion on running wheel 23 3.9 STN-DBS modulates MO population activity in a frequency-dependent manner but does not link to behavioral improvement 24 3.10 STN-DBS modulates single neuron activity in a layer-wised distinct manner 25 3.11 Antidromic activation of MO neurons by STN-DBS observed via calcium imaging 26 3.12 Frequency-dependent modulation of L5 antidromic neuronal activity in anesthetized mice 27 3.13 Layer 2/3 neuronal activity is not directly from antidromic activation 28 3.14 MO population activity under STN-DBS show layer specificity 29 3.15 Single cell frequency responsiveness is not linearly correlated with DBS-frequency 30 3.16 Population state-space analysis for neural activity patterns 31 3.17 Frequency-dependent neural states in L5 align with naturally occurring movement patterns 32 Chapter 4 Conclusion 34 Chapter 5 Discussion 35 5.1 Mechanisms underlying frequency-dependent cortical responses 35 5.1.1 L5 cortical dynamics under STN-DBS and excitatory effect 35 5.1.2 Cortical L5 neuronal dynamics and possible interneuron recruitment 36 5.1.3 Frequency-selective pattern switching in L2/3 37 5.1.4 Implication of pattern selection 38 5.1.5 Ensemble labeling 39 Chapter 6 Figures 41 Chapter 7 References 78 Chapter 8 Appendix 82 8.1 2022 Tsfn poster 82 8.2 2023 IMB retreat poster 83 8.3 2024 GRC poster 84 8.4 2024 Tsfn/ 2025 EMBO poster 85 8.5 2025 life science poster competition 86 | - |
| dc.language.iso | en | - |
| dc.subject | 視丘下核 | zh_TW |
| dc.subject | 腦深層電刺激 | zh_TW |
| dc.subject | 運動皮質 | zh_TW |
| dc.subject | 神經動態 | zh_TW |
| dc.subject | 帕金森氏症 | zh_TW |
| dc.subject | 頻率依賴性 | zh_TW |
| dc.subject | Motor cortex | en |
| dc.subject | Subthalamic nucleus | en |
| dc.subject | Frequency dependency | en |
| dc.subject | Parkinson’s disease | en |
| dc.subject | Neuronal dynamics | en |
| dc.subject | Deep brain stimulation | en |
| dc.title | 頻率調控視丘下核深層腦刺激對運動皮質動態的差異性調節 | zh_TW |
| dc.title | Differential Modulation of Motor Cortex Dynamics by Frequency-Tuned STN Deep Brain Stimulation | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 林士傑;陳摘文;徐經倫;陳瓊珠 | zh_TW |
| dc.contributor.oralexamcommittee | Shih-Chieh Lin;Tsai-Wen Chen;Ching-Lung Hsu;Chiung-Chu Chen | en |
| dc.subject.keyword | 視丘下核,腦深層電刺激,運動皮質,神經動態,帕金森氏症,頻率依賴性, | zh_TW |
| dc.subject.keyword | Subthalamic nucleus,Deep brain stimulation,Motor cortex,Neuronal dynamics,Parkinson’s disease,Frequency dependency, | en |
| dc.relation.page | 86 | - |
| dc.identifier.doi | 10.6342/NTU202504301 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2025-08-15 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 基因體與系統生物學學位學程 | - |
| dc.date.embargo-lift | 2030-08-07 | - |
| 顯示於系所單位： | 基因體與系統生物學學位學程 | |
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