Dendritic Ion Channels Shape Motoneuron Responses

树突离子通道塑造运动神经元反应

• 批准号: 6836412
• 负责人: ANNA M TAYLOR
• 金额: $ 4.3万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6836412
• 关键词: NMDA receptors; calcium channel; cell component structure /function; computational neuroscience; computer simulation; dendrites; electrophysiology; fluorescence microscopy; infrared microscopy; intermolecular interaction; laboratory rat; membrane channels; model design /development; motor neurons; neuroanatomy; neuromuscular function; neuromuscular transmission; neuroregulation; postdoctoral investigator; potassium channel; protein localization; protein structure function; sodium channel; synapses

DESCRIPTION (provided by applicant): Motoneurons have an important role in translating the neural signal from supraspinal and reflex sources to a frequency code for the contraction of muscle. However, synaptic input alone cannot account for the signal that reaches the muscle fibers. Active dendritic conductances in the dendrites of motoneurons are essential for the generation of sufficient current to drive the motoneuron. The distribution and types of active dendritic conductances dictate the summation of input and resulting current that reaches the soma. Unlike cortical neurons, however, the spatial location of various dendritic conductances are still largely uncharacterized. Theoretically, the most reliable transfer of information would be through linear summation of synaptic inputs. The hypothesis is that ion channels are spatially distributed in the dendrites of motoneurons to allow for the linear summation of synaptic input current. The hypothesis will be tested using a combination of multiphoton fluorescence imaging and optimization of neuron models using a genetic algorithm. This research is important for the neurodegenerative disease ALS, which may be caused by excitotoxicity due to an immune reaction to calcium channels and is particularly marked in hypoglossal motoneurons.

描述（由申请人提供）：运动神经元在将来自脊髓上和反射源的神经信号转换为肌肉收缩的频率代码方面具有重要作用。然而，突触输入本身并不能解释到达肌肉纤维的信号。运动神经元树突中的活跃树突电导对于产生足够的电流来驱动运动神经元至关重要。活性树突电导的分布和类型决定了到达体细胞的输入和所得电流的总和。然而，与皮质神经元不同的是，各种树突电导的空间位置在很大程度上仍然是未知的。理论上，最可靠的信息传递是通过突触输入的线性求和。假设离子通道在运动神经元的树突中空间分布，以允许突触输入电流的线性求和。该假设将通过多光子荧光成像和使用遗传算法优化神经元模型的组合进行测试。这项研究对于神经退行性疾病 ALS 很重要，这种疾病可能是由钙通道免疫反应引起的兴奋性毒性引起的，在舌下运动神经元中尤为明显。