Dendritic integration in medial superior olivary neurons

描述（由申请人提供）：在哺乳动物的大脑中，内侧上橄榄（MSO）形成了一条主要的上行听觉通路，传递低频声音的颞结构和位置信息。从水平面上偏离中心位置发出的声音到达两只耳朵的时间略有不同。MSO的突出或主要神经元以几十微秒的分辨率计算这些时间差异。然后，MSO神经元将这些线索精确地传递到更高的听觉中枢，在那里它们与用于定位声音的其他线索结合在一起。在MSO主神经元中，双侧突触输入的整合发生在树突中，树突是接受大多数兴奋性突触接触的狭窄分支结构。与其他神经元一样，突触活动沿着树突传播到体细胞和轴突。在轴突中，经过处理的突触活动被转化为电脉冲，然后沿着轴突传递到神经递质释放的部位。在对非听觉脑区的研究中，最近对树突的膜片钳记录技术的应用表明，突触活动与多种树突离子通道相互作用，赋予神经元复杂的计算特性。虽然MSO神经元的生物物理特性似乎专门用于快速和精确的神经信号传导，但树突在处理双耳听觉信息中的作用仍未得到实验的探索。本研究将首次采用树突膜片钳记录技术来研究哺乳动物中枢听觉神经元突触输入的整合。MSO主要神经元将在沙鼠脑切片可视化使用差示干涉对比视频显微镜。电生理记录将从MSO神经元树突中进行，以检查a)突触活动如何在树突中累积，b)评估突触输入和电压门控离子通道之间的相互作用，以及c)量化树突结构对突触活动的电影响。电生理学方法也将检查沿体细胞和树突的低阈值钾通道的亚型表达、空间分布和功能作用。这些通道对动作电位信号的阈值和精度影响最大，动作电位信号是声音定位线索处理的关键因素。

DESCRIPTION (provided by applicant): In the mammalian brain, the medial superior olive (MSO) forms a major ascending auditory pathway that conveys information about the temporal structure and location of low-frequency sounds. Sounds arising from off-center locations along the horizontal plane reach the two ears at slightly different times. The projecting, or principal neurons of the MSO compute these temporal differences with a resolution on the order of tens of microseconds. MSO neurons then transmit these cues with precision to higher auditory centers where they are combined with other cues used in the localization of sounds. Within MSO principal neurons, the integration of bilateral synaptic inputs occurs in the dendrites, the narrow branched structures that receive the majority of excitatory synaptic contacts. As in other neurons, synaptic activity is propagated along the dendrites to the soma and axon. In the axon, the processed synaptic activity is translated into electrical impulses that are then conveyed along the axon to the sites of neurotransmitter release. In studies of non-auditory brain areas, the recent application of patch-clamp recording techniques to dendrites has revealed that synaptic activity interacts with a diverse array of dendritic ion channels, endowing neurons with complex computational properties. While the biophysical properties of MSO neurons appear specialized for rapid and precise neural signaling, the role of dendrites in processing binaural auditory information remains unexplored experimentally. The present study will, for the first time, employ dendritic patch-clamp recording techniques to study the integration of synaptic input in mammalian central auditory neurons. MSO principal neurons will be visualized in gerbil brain slices using differential interference contrast video microscopy. Electrophysiological recordings will be made from MSO neuron dendrites to examine a) how synaptic activity sum in the dendrites, b) to assess interactions between synaptic input and voltage-gated ion channels, and c) to quantify the electrical influence of dendritic structure on synaptic activity. Electrophysiological approaches will also examine the subtype expression, spatial distribution, and functional role of low-threshold potassium channels along the soma and dendrites. These channels have the strongest impact on the threshold and precision of action potential signaling, critical factors underlying the processing of sound localization cues.