Biophysical properties and function of primary auditory neurons

描述(由申请人提供)：我们的目标是了解听觉神经元的固有离子通道属性是否塑造了它们的功能。具体地说，我们想要了解一些I型听觉神经元如何编码低强度的声音，而另一些则编码高强度的声音。形成这些反应特征的机制尚不清楚，但可能依赖于突触前和突触后的特化。来自与世隔绝的 听觉神经元的体细胞表明，离子通道属性的多样性可能会影响它们的反应，但尚未证明明显的相关性。为了建立直接的相关性，我们建议使用半完整的大鼠耳蜗体外标本，以保留螺旋神经节和Corti器官之间的解剖和功能联系。该方法结合了全细胞膜片钳记录、神经元标记、形态计量学分析和计算模型，以探索初级听觉传入神经元固有的生物物理特性如何塑造其生理反应。此外，由于我们的实验来自于听力开始前后的动物，我们可以表征I型听神经元在生物物理和形态上成熟为不同功能群的时间过程。

DESCRIPTION (provided by applicant): Our goals are to understand whether the intrinsic ion-channel properties of auditory neurons shape their function. Specifically, we want to understand how some groups of Type I auditory neurons encode low-intensity sounds whereas others encode high-intensity sounds. The mechanisms shaping these response features are unknown but are likely to rely on both pre- and post-synaptic specializations. Recordings from the isolated somata of auditory neurons suggest that diversity in ion channel properties may influence their response, but a clear correlation has not been demonstrated. To make direct correlations, we propose to use semi-intact in vitro preparations of rat cochleae that preserve the anatomical and functional connections between the spiral ganglion and organ of Corti. The approach brings together whole-cell patch-clamp recordings, neuronal labeling, morphometric analysis, and computational modeling to explore how the biophysical properties intrinsic to primary auditory afferent neurons shape their physiological responses. Furthermore, because our experiments are from animals at ages before and after the onset of hearing, we can characterize the time course over which Type I auditory neurons' mature biophysically and morphologically into distinct functional groups.