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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：
10658870
负责人：
Yutaka Yoshida
金额：
$ 54.24万
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/10658870
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 Genetic 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 Vertebral column Virus 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 skills 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.

在运动行为过程中，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由存在于所有哺乳动物中的脊髓中间神经元调节，脊髓中间神经元又连接到其他脊髓神经元以及来自大脑的各种类型的下行神经元 (CS)神经元（CSNs）。位于运动皮层的CSNs连接脊髓中间神经元以控制运动神经元活动，从而协调屈肌和伸肌肢体肌肉的活动，以控制熟练的动作。虽然我们和其他人主要关注CSN通过轴突的输出，也通过树突接受突触前神经元的输入。然而，识别和对CSN的突触前神经元（pre-CSN）的功能的理解仍然有限。我们开发狂犬病病毒为基础的检测，以确定前CSN。我们假设每个前CSN群体将是明显激活以控制熟练运动和肌肉激活的离散阶段。来测试我们假设，在目标1中，我们将映射大脑中CSN的突触前伴侣。我们将进一步确定这些连接是功能性的（目标2）。最后，我们将确定前CSNs如何控制前肢熟练运动和肌肉活动（目标3）。这些结果将提供必要的框架，不仅定义脊髓运动回路，以及随后开发新的靶向干预措施，以治疗运动残疾。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Molecular mechanisms underlying monosynaptic sensory-motor circuit development in the spinal cord.

DOI：
10.1002/dvdy.24611
发表时间：
2018-04
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
0
作者：
Imai F;Yoshida Y
通讯作者：
Yoshida Y

Corticospinal Pathways and Interactions Underpinning Dexterous Forelimb Movement of the Rodent.

DOI：
10.1016/j.neuroscience.2020.05.050
发表时间：
2020-12-01
期刊：
Neuroscience
影响因子：
3.3
作者：
Basista MJ;Yoshida Y
通讯作者：
Yoshida Y

Converging integration between ascending proprioceptive inputs and the corticospinal tract motor circuit underlying skilled movement control.

DOI：
10.1016/j.cophys.2020.10.007
发表时间：
2021-03
期刊：
Current opinion in physiology
影响因子：
2.5
作者：
Kalambogias J;Yoshida Y
通讯作者：
Yoshida Y

Silencing spinal interneurons inhibits immune suppressive autonomic reflexes caused by spinal cord injury.

DOI：
10.1038/nn.4289
发表时间：
2016-06
期刊：
Nature neuroscience
影响因子：
25
作者：
Ueno M;Ueno-Nakamura Y;Niehaus J;Popovich PG;Yoshida Y
通讯作者：
Yoshida Y

Semaphorin-Mediated Corticospinal Axon Elimination Depends on the Activity-Induced Bax/Bak-Caspase Pathway.

信号蛋白介导的皮质脊髓轴突消除取决于活动诱导的 Bax/Bak-Caspase 通路。

DOI：
10.1523/jneurosci.3190-18.2020
发表时间：
2020
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Gu,Zirong;Koppel,Natasha;Kalamboglas,John;Alexandrou,Gabriella;Li,Jie;Craig,Corey;Simon,DavidJ;Tessier-Lavigne,Marc;Baccei,MarkL;Martin,JohnH;Yoshida,Yutaka
通讯作者：
Yoshida,Yutaka