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）：运动神经元在将神经信号从脊柱上和反射源转化为肌肉收缩的频率代码方面具有重要作用。但是，仅突触输入无法解释到达肌肉纤维的信号。运动神经元树突中的活性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。主动树突电导的分布和类型决定了输入的总和，并产生的电流达到了SOMA。但是，与皮质神经元不同，各种树突电导的空间位置仍然很大程度上没有表征。从理论上讲，最可靠的信息传输将是通过突触输入的线性求和。假设是离子通道在运动神经元的树突中分布在空间上，以允许突触输入电流的线性总和。该假设将使用遗传算法的多光子荧光成像和对神经元模型的优化进行检验。这项研究对于神经退行性疾病ALS很重要，这可能是由于对钙通道的免疫反应引起的兴奋性毒性而引起的，并且在降低性运动神经元中尤其明显。