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

我们将研究帕金森氏病小鼠模型（PD）中的运动丘脑如何参与 将基底神经节产生的帕金森氏症活动模式传输到大脑皮层。我们将使用 在麻醉和 清醒小鼠确定病理活动模式的存在及其之间的关系 结构。该提案的一种优势包括使用体内细胞内丘脑记录，这些记录 将使我们能够检查以下假设：PD中观察到的强大基底神经节爆发活动将触发 丘脑后的后反弹爆发。先前的工作表明，这种基底神经节中的这种破裂 是PD中病理活性模式的特征之一，但是该活动的传播 通过丘脑到皮质的经历尚不清楚。我们将对特定机制进行详细分析 在大脑切片制剂中小鼠的运动丘脑中突触整合，我们在其中测试 帕金森尼投入模式控制动作潜在的启动。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毒蕈碱 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 病理活性从基底神经节穿过丘脑到皮质的传播。 该项目与整个Emory Udall Center Grant的其他项目紧密整合 应用程序：我们与项目2分享对丘脑处理的重点，将在灵长类动物中进行检查 用MPTP渲染帕金森尼人。我们与项目3共享PD的VMAT2L0鼠标模型，它将在其中 用于确定可能的神经保护治疗策略。我们对病理电气的分析 米勒（Miller）博士在埃默里（Emory）开发的VMAT2L0小鼠中的活动模式将有助于对此进行验证 模型。我们获得了要测试的药理学化合物，以对丘脑加工产生特定作用 通过我们与项目4的互动。上面提到的这些化合物是有希望的新颖特定的 受体激动剂和拮抗剂以及其他尚不可用的通道阻滞剂