The Role of Mouse Motor Thalamus Realying Basal Ganglia Outflow

小鼠运动丘脑在基底神经节流出中的作用

• 批准号: 8544549
• 负责人: DIETER JAEGER
• 金额: $ 12.53万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8544549
• 关键词: Action Potentials; Address; Agonist; Antiparkinson Agents; Applications Grants; Basal Ganglia; Behavior; Blood - brain barrier anatomy; Brain; Calcium; Calcium Channel; Calcium Channel Blockers; Cell Nucleus; Cerebral cortex; Characteristics; Disease; Electric Stimulation; Frequencies; Human; Injection of therapeutic agent; Intervention; Investigation; Lead; Lesion; Link; Membrane Potentials; Modeling; Motor; Motor Cortex; Mus; Muscarinic Acetylcholine Receptor; Muscarinics; Neurons; Operative Surgical Procedures; Optics; Output; Parkinson Disease; Parkinsonian Disorders; Patients; Pattern; Pharmaceutical Preparations; Pharmacological Treatment; Preparation; Primates; Process; Property; Publications; Rodent; Rodent Model; Role; Shapes; Signal Transduction; Slice; Structure; Structure of subthalamic nucleus; Symptoms; Synapses; Techniques; Testing; Thalamic structure; Therapeutic; Transgenic Mice; Universities; Validation; Work; awake; behavior test; channel blockers; disease transmission; in vivo; innovation; interest; mouse model; novel; optogenetics; public health relevance; receptor; response; tool; transmission process; treatment strategy

We will examine how the motor thalamus In mouse models of Parkinson's disease (PD) Is Involved In transmitting Parkinsonian activity patterns generated In the basal ganglia to the cerebral cortex. We will use simultaneous electrophysiological recordings from basal ganglia, thalamus, and cortex In anesthetized and awake mice to determine the presence of pathological activity patterns, and their relations between structures. One strength of the proposal consists of the use of in vivo intracellular thalamic recordings, which will allow us to examine the hypothesis that strong basal ganglia bursting activity observed In PD will trigger postlnhibitory rebound bursting In thalamus. Previous work suggests that such bursting in the basal ganglia Is one of the characteristics of pathological activity patterns in PD, but the transmission of this activity through thalamus to cortex remains unclear. We will carry out a detailed analysis of the specific mechanisms of synaptic integration in motor thalamus of the mouse In the brain slice preparation, where we test the control of action potential initiation by Parkinsonian patterns of Input. Finally, we will determine whether pharmacological compounds known to Interact with thalamic cellular properties (M1 and M4 muscarinic receptor agonists or antagonists or selective Cav3 calcium channel blockers) can be used to reduce the transmission of pathological activity from the basal ganglia through thalamus to cortex. This project Is tightly Integrated with the other projects of the overall Emory Udall Center grant application: We share the focus on thalamic processing with project 2, where It will be examined In primates rendered parkinsonian with MPTP. We share the VMAT2L0 mouse model of PD with project 3, where It will be used to determine possible neuroprotective treatment strategies. Our analysis of pathological electrical activity patterns In the VMAT2L0 mouse developed by Dr. Miller at Emory will aid in the validation of this model. We obtain the pharmacological compounds to be tested for specific effect on thalamic processing through our interactions with project 4. These compounds mentioned above are promising novel specific receptor agonists and antagonists as well as channel blockers that are not otherwise available

我们将研究帕金森病(PD)小鼠模型中的运动丘脑是如何参与 将基底节产生的帕金森氏症活动模式传递到大脑皮层。我们将使用 麻醉大鼠基底神经节、丘脑和皮质的同步电生理记录 确定清醒小鼠是否存在病理活动模式，以及它们之间的关系 结构。该提议的一个优点是使用体内细胞内丘脑记录，这是 将使我们能够检验这样的假设，即在帕金森病患者中观察到的强烈的基底节爆发活动将触发 抑制后反弹在丘脑爆发。先前的研究表明，这种基底节的爆裂 是帕金森病病理性活动模式的特征之一，但这种活动的传递 通过丘脑到大脑皮层的通路仍不清楚。我们将对具体机制进行详细分析 在小鼠的脑片制备中，我们测试了小鼠运动丘脑的突触整合 帕金森输入模式对动作电位启动的控制。最后，我们将确定是否 已知与丘脑细胞特性相互作用的药理化合物(M1和M4毒鼠强 受体激动剂或拮抗剂或选择性Cav3钙通道阻滞剂)可用于减少 病理活动从基底节通过丘脑传递到皮质。 该项目与埃默里·尤德尔中心赠款的其他项目紧密结合在一起 应用：我们与项目2共同关注丘脑处理，在项目2中，将在灵长类动物身上进行研究 用MPTP呈现帕金森综合症。我们与项目3共享PD的VMAT2L0小鼠模型，它将在那里 用于确定可能的神经保护性治疗策略。我们对病理电信号的分析 Emory的Miller博士开发的VMAT2L0小鼠的活动模式将有助于验证这一点 模特。我们得到了要测试的药理化合物，以测试对丘脑处理的特定影响 通过我们与项目4的相互作用。上述这些化合物是有希望的新的特定的 受体激动剂和拮抗剂以及以其他方式无法获得的通道阻滞剂