Dendritic Ion Channels Shape Motoneuron Responses

描述(由申请人提供)：运动神经元在将来自脊髓上和反射来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，仅靠突触输入并不能解释到达肌肉纤维的信号。运动神经元树突中活跃的树突电导对于产生足够的电流来驱动运动神经元是必不可少的。有效树枝状电导的分布和类型决定了到达体层的输入电流和产生的电流的总和。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未确定。从理论上讲，最可靠的信息传递将是通过突触输入的线性求和。假设离子通道在空间上分布在运动神经元的树突中，以允许突触输入电流的线性求和。这一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验证。这项研究对神经退行性疾病ALS很重要，这种疾病可能是由于对钙通道的免疫反应而引起的兴奋性毒性，在舌下运动神经元中尤为明显。

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.