Pontine motor circuits

脑桥运动电路

基本信息

批准号：
8418738
负责人：
JUN LU
金额：
$ 30.82万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-02-01 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8418738
关键词：
Accounting Acute Address Animals Area Attention Band Cell Basal Ganglia Behavior Behavioral Bilateral Bradykinesia Brain Brain Stem Cataplexy Cell Nucleus Cells Chemical Stimulation Chemicals Choline Cytomegalovirus Data Data Analyses Defect Development Devices Dextrans Diagnostic Disease Dopamine Dopamine D2 Receptor Dorsal Electric Stimulation Electroencephalography Embryonic Lethal Mutation Emotional Exons Felis catus Festinating Gait Flexor Freezing Functional disorder Future Gait Gait abnormality Genes Genetic Genetic Recombination Glutamates Goals Horns Ibotenic Acid Image Immunohistochemistry Immunotoxins Implant In Situ Hybridization Individual Injection of therapeutic agent Injury Knock-out Knockout Mice Label Laboratories Lateral Lesion Levodopa Lewy Body Dementia Limb structure Link Location Locomotion Maps Medial Mediating Messenger RNA Midbrain structure Modeling Motor Motor Neurons Movement Disorders Multiple System Atrophy Mus Muscle Muscle Tonus Nerve Degeneration Neurodegenerative Disorders Neurons Outcome Output Parkinson Disease Parkinsonian Disorders Pathway interactions Pattern Pedunculopontine Tegmental Nucleus Pharmacological Treatment Physiological Pontine structure Population Positioning Attribute Posture Progressive Supranuclear Palsy Rattus Reporting Research Rest Tremor Reticular Formation Rewards Role Secondary to Series Signal Transduction Site Sleep Specificity Spinal Spinal Cord Stimulus Structure Substantia nigra structure Suid Herpesvirus 1 Symptoms System Techniques Tegmentum Mesencephali Testing Therapeutic Time Tongue Tracer Transfection Transferase Ventral Horn of the Spinal Cord Video Recording Virus Latency Walking adeno-associated viral vector base behavior change cholinergic cholinergic neuron design dextran dopaminergic neuron drinking feeding gamma-Aminobutyric Acid hypocretin killings motor control neural circuit neurochemistry neurogenetics neurotransmission orexin B receptor pars compacta programs promoter receptor recombinase research study response synucleinopathy therapeutic development therapeutic target tibialis anterior muscle transmission process vesicular glutamate transporter 2

项目摘要

DESCRIPTION (provided by applicant): Parkinsonism characterizes the motor symptoms of Parkinson's disease and other related neurodegenerative conditions (e.g., multiple system atrophy, progressive supranuclear palsy and dementia with Lewy bodies) to varied degrees. Parkinsonism includes resting tremor, rigidity, postural abnormalities, gait disturbances and bradykinesia/akinesia. Although traditional accounts emphasize the role of reduced dopamine (DA) transmission in the basal ganglia (secondary to loss of midbrain A9 dopamine neurons) in the motoric defects of these disorders, more recent data support the concept that degeneration of brainstem circuitry beyond the midbrain DA group may be important contributors to the development of parkinsonism and therefore present a potential therapeutic target. The objective of the present proposal is to delineate the role of the mesencephalic locomotor region (MLR), a pontine structure linking basal ganglia output with spinal cord motor circuitry, in the pathophysiology of Parkinsonism. To accomplish this objective, we have designed three specific aims that combine neuroanatomical, neurochemical and neurogenetic approaches to delineate the roles of the MLR and two adjacent areas of the lateral pontine tegmentum, the pedunculopontine tegmental nucleus (PPT) and the midbrain extrapyramidal area (MEA), in motor control. Based upon our preliminary data, we hypothesize two major pathways linking key basal ganglia output nuclei with spinal cord motor circuitry: (1) an extensor circuit regulating postural tone by extensor muscles in the limbs and (2) a flexor circuit, necessary for locomotion and to perform specific tasks. The extensor circuit utilizes a presumably dopaminergic input from the substantia nigra pars compacta (SNc) to the ventral MLR while the extensor circuit is comprised of a presumably GABAergic projection from the substantia nigra pars reticulata (SNr) to the glutamatergic MEA, and from there to neurons in the dorsal MLR. Both the extensor and flexor circuits are then served by glutamatergic neurons that directly innervate the spinal cord. By elucidating the neuroanatomic connections and neurochemical mechanisms by which the mesencephalic locomotor region relays basal ganglia output to spinal motor cord circuitry, therapeutic and diagnostic strategies may be developed for individuals suffering from Parkinsonism and possibly other movement disorders such as cataplexy.

描述（由申请人提供）：帕金森氏症将帕金森氏病的运动症状和其他相关的神经退行性疾病（例如，多个系统萎缩，进行性的上核性麻痹和带有路易尸体的痴呆症）表征为各种程度。帕金森氏症包括静止震颤，僵化，姿势异常，步态障碍和心动肌/阿肯尼亚。尽管传统记录强调了在基底神经节中减少多巴胺（DA）传播的作用（次要中脑A9多巴胺神经元的丧失）在这些疾病的摩托缺陷中的作用，但最新数据支持以下概念，即中脑DA组的退化脑部电路的退化可能是parkinsonism and Parkinsonism and the Parkinsiss and Targe Interage的重要促进者。本提案的目的是描述中脑运动区域（MLR）的作用，这是一种将基底神经节输出与脊髓运动电路联系起来的庞蒂汀结构，在帕金森主义的病理生理学中。为了实现这一目标，我们设计了三个具体目标，它们结合了神经解剖学，神经化学和神经遗传学方法来描述MLR的作用以及pontaline Teggentum的两个邻近区域，ponculopontine temulopontine Tementaline Tegmetal tempemtal inucleus（PPT）（PPT）和中脑外脑外胞胸区域（Miedbrain Extrapyramidal（Mea）（Meaea）。基于我们的初步数据，我们假设将关键基底神经节输出核与脊髓运动电路联系起来的两种主要途径：（1）伸肌电路通过四肢中的伸肌肌肉调节姿势姿势，（2）屈肌电路（2）术中所需的屈肌和执行特定任务。伸肌电路利用了从底虫底层compacta（SNC）到腹MLR的大概多巴胺能输入，而伸肌电路则由伸肌电路组成，这些电路由大概是来自黑质的nigra pars pars reticulata（snr）到Glutamagic Mea和Neurons和Neurons的Nigra Pars pars reticulata（SNR）和Neurons neurons和Neurons neurons to neurons of to neurons to n do n neurons，然后，伸肌和屈肌电路均由谷氨酸能神经元直接支配脊髓。通过阐明中脑运动区域的神经解剖连接和神经化学机制，可以为患有Parkinsonism和其他可能的其他运动障碍（如震惊的）而开发中脑运动区域的基础神经节输出到脊柱运动绳索回路，治疗和诊断策略。