Presynaptic partners of corticospinal neurons to control skilled movements

皮质脊髓神经元的突触前伙伴控制熟练的运动

基本信息

批准号：
10434888
负责人：
Yutaka Yoshida
金额：
$ 58.37万
依托单位：
WINIFRED MASTERSON BURKE MED RES INST
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-15 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10434888
关键词：
Address Adult Affect Antibodies Area Axon Behavior Biological Assay Brain Calcium Cerebral cortex Data Dendrites Development Disease Electromyography Electrophysiology (science)Exhibits Extensor Flexor Forearm Forelimb Funding Goals Human Image Impairment Injury Interneurons Interruption Intervention Limb structure Maintenance Mammals Maps Methods Molecular Motor Motor Activity Motor Cortex Motor Neurons Motor Skills Movement Mus Muscle Neurons Output Parkinson Disease Pattern Phase Population Proprioceptor Rabies virus Research Rodent Role Spinal Spinal Cord Spinal Ganglia Spinal cord injury Stroke Synapses System Testing Thalamic structure Therapeutic Time Virus base disability effective therapy grasp imaging study motor behavior motor control motor disorder mouse development neural circuit novel novel therapeutics optogenetics presynaptic presynaptic neurons sensory cortex therapeutic target therapy design

项目摘要

The highly orchestrated muscle activation sequences during motor behaviors are achieved directly through the fine-tuned firing of motor neurons in the ventral spinal cord. These motor neurons are mainly regulated by spinal interneurons present in all mammals, which are, in turn, connected to other spinal neurons as well as various types of descending neurons from the brain including corticospinal (CS) neurons (CSNs). CSNs located in the motor cortex connect to spinal interneurons to control motor neuron activity in all species, and thereby coordinate the activity of flexor and extensor limb muscles to control skilled movements. Although we and others mainly focused on outputs of CSNs through their axons, CSNs also receive inputs from their presynaptic neurons through their dendrites. However, the identification and understanding of the function of presynaptic neurons of CSNs (pre-CSNs) remains limited. We developed rabies virus-based assays to identify pre-CSNs. We hypothesize that each population of pre-CSNs will be distinctly activated to control discrete phases of skilled movements and muscle activation. To test our hypothesis, in Aim 1 we will map presynaptic partners of CSNs in the brain. We will further determine whether those connections are functional (Aim 2). Finally, we will determine how pre-CSNs control forelimb skilled movements and muscle activity (Aim 3). These results will provide the necessary framework for not only defining spinal motor circuitry, but also subsequent development of novel targeted interventions to treat motor disabilities.

运动行为期间高度协调的肌肉激活序列是直接通过腹侧脊髓中运动神经元的微调放电来实现。这些电机神经元主要受所有哺乳动物中存在的脊髓中间神经元的调节，而脊髓中间神经元又与其他脊髓神经元以及来自大脑的各种类型的下行神经元，包括皮质脊髓神经元 (CS) 神经元 (CSN)。位于运动皮层的 CSN 连接脊髓中间神经元来控制运动所有物种的神经元活动，从而协调肢体屈肌和伸肌的活动来控制熟练的动作。虽然我们和其他人主要关注 CSN 通过轴突的输出，但 CSN 还通过树突接收来自突触前神经元的输入。然而，识别和对 CSN 突触前神经元（前 CSN）功能的了解仍然有限。我们开发了基于狂犬病病毒的检测来识别前 CSN。我们假设每个前 CSN 群体都是明显激活以控制熟练运动和肌肉激活的离散阶段。来测试我们的假设，在目标 1 中，我们将绘制大脑中 CSN 的突触前伙伴图。我们将进一步确定是否这些连接有效（目标 2）。最后，我们将确定预 CSN 如何控制前肢熟练运动和肌肉活动（目标 3）。这些结果不仅将提供必要的框架定义脊髓运动回路，而且随后开发新的有针对性的干预措施来治疗运动残疾。