Functional Dissection of Neural Circuitry in Temporally Patterned Deep Brain Stimulation

时间模式深部脑刺激中神经回路的功能解剖

• 批准号: 10046820
• 负责人: Chunxiu Yu
• 金额: $ 46.37万
• 依托单位: MICHIGAN TECHNOLOGICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10046820
• 关键词: Adverse effects; Anatomy; Behavioral; Behavioral Assay; Biological Markers; Biomedical Research; Bradykinesia; Cells; Clinical; Clinical Research; Clinical effectiveness; Cognitive; Coupling; Deep Brain Stimulation; Development; Dissection; Electrophysiology (science); Environment; Forelimb; Foundations; Frequencies; Globus Pallidus; Goals; Lateral; Light; Mental disorders; Michigan; Modeling; Motor; Neurons; Neurosciences Research; Opsin; Parkinson Disease; Parkinsonian Disorders; Pathologic; Pattern; Performance; Phase; Physiologic pulse; Rattus; Reporting; Research; Research Infrastructure; Rodent Model; Role; Step Tests; Structure of subthalamic nucleus; Testing; Thalamic Nuclei; Thalamic structure; Therapeutic; Therapeutic Effect; Training; Universities; base; design; effective therapy; improved; innovation; insight; interest; motor deficit; motor symptom; nervous system disorder; neural circuit; neuromechanism; neuropsychiatric disorder; novel; optimal treatments; optogenetics; reduce symptoms; relating to nervous system; side effect; treatment strategy; undergraduate student

Deep brain stimulation (DBS) is an established treatment for various neurological and psychiatric disorders including Parkinson’s disease (PD). Subthalamic nucleus (STN) and globus pallidus interna (GPi) are current anatomical targets and clinically effective for DBS in PD. Clinical studies reported no significant difference in effective treatment between these two targets, although additional interest has been prompted in GPi-DBS due to increased concerns about cognitive and behavioral side effects of STN-DBS. The therapeutic effects of DBS are highly dependent on stimulation parameters. With the selection of appropriate stimulation amplitude and pulse duration, high frequencies of DBS alleviate PD motor symptoms. Recent studies demonstrated that the effects of DBS were also strongly dependent on the timing between stimulation pulses (temporal pattern). Optimized temporal patterns of stimulation at a lower average frequency could relieve motor deficits and reduce adverse side effects. Despite the promising clinical benefits, the lack of understanding of the effects of temporal patterns of DBS on neuronal and behavioral dynamics limits the development of this promising treatment strategy as well as optimal selection of DBS targets. The goal of our research is to reveal the relationships between specific temporal patterns of DBS in STN and GPi and (i) neural activity in STN and GPI associated circuits and (ii) motor function in PD. We will combine computational design, optogenetic manipulation, electrophysiological recording, and behavioral assays to dissect and optimize the therapeutic effects of temporally patterned STN-DBS and GPi-DBS in a rodent model of PD. Our specific aims are to: (1) Design and validate temporal patterns of optogenetic STN-DBS and GPi-DBS to treat parkinsonian motor symptoms; (2) Determine the relationship between neural activity in the STN-thalamic or GPi-thalamic neural circuits and motor function during temporally patterned optogenetic STN-DBS and GPi-DBS. The results from this proposed research will shed light on the functional role of the temporal patterns of DBS in PD treatment. A better understanding of how temporally patterned DBS exerts its therapeutic effects will make a significant contribution to optimal target selection and the development of novel treatment strategies to improve the efficacy and efficiency of DBS in PD and other neurological and psychiatric disorders.

脑深部电刺激（DBS）是一种治疗各种神经和精神疾病的有效方法