Functional organization of the auditory corticocollicular system

 描述（由申请人提供）：从声音中提取意义的能力，即使在降级时，对正常听力至关重要。听觉系统在声学挑战性情况下采用的一个关键策略是使用上下文线索来消除杂乱信号的歧义。重要的是，许多患有语言相关疾病的患者，如失语症，自闭症和阅读障碍，很难利用这些上下文线索。高级信息可以用来塑造低级感觉处理的神经机制还不清楚。这种处理的潜在基底是从听觉系统的几乎每一个层次发出的巨大的自上而下的投射系统。在这个项目中，我们将提供一个最大的这些预测之一的功能特性：听觉皮质丘系统。皮质丘系统可以迅速而深刻地改变下丘神经元的调谐，但其组织的关键方面尚不清楚。 我们假设该系统包括至少两个功能不同的子系统;一个来自皮质层5，另一个来自皮质层6。使用小鼠模型，将重建并比较投射到下丘小区域的第5层和第6层神经元的皮质分布。我们的早期数据表明，来自第6层的输入来自比第5层更广泛的区域，并且倾向于在听觉皮层的非主要部分占主导地位。此外，我们将结合联合收割机在体内经颅黄素蛋白自体荧光成像与定量神经元重建，以比较第5层与第6层皮质投射到下丘的投射模式。最后，我们将使用一种新的皮质丘脑片制备和激光光刺激，比较皮质丘第5层和第6层突触的突触特性。该项目的成功完成将提供这一重要途径的第一个电路级表征，并将为更好地理解自上而下的调节系统如何在沟通障碍期间崩溃奠定基础。

 DESCRIPTION (provided by applicant): The ability to extract meaning from sounds, even when degraded, is critical for normal hearing. A key strategy employed by the auditory system during acoustically-challenging situations is the use of contextual cues to disambiguate cluttered signals. Importantly, many patients with language-related disorders, such as aphasia, autism and dyslexia, have difficulties harnessing such contextual cues. The neural mechanisms by which high-level information can be used to shape lower-level sensory processing are not yet known. A potential substrate for this type of processing is the massive top-down projection system emanating from virtually every level of the auditory system. In this project, we will provide a functional characterization of one of the largest of these projections: the auditory corticocollicular system. The corticocollicular system can rapidly and profoundly change the tuning of neurons in the inferior colliculus, but key aspects about its organization are not known. We hypothesize that this system comprises at least two functionally distinct sub- systems; one from cortical layer 5 and another from cortical layer 6. Using the mouse model, the cortical distribution of layer 5 and 6 neurons that project to small regions of the inferior colliculus willbe reconstructed and compared. Our early data suggest that input from layer 6 emanates from a more widespread area than layer 5 and tends to predominate in the non-primary parts of the auditory cortex. In addition, we will combine in vivo transcranial flavoprotein autofluoresence imaging with quantitative neuronal reconstructions to compare the projection patterns of layer 5 vs. layer 6 cortical projections to the inferior colliculus. Finally, using a novel corticocolliculr brain slice preparation and laser photostimulation, we will compare the synaptic properties of layer 5 and 6 corticocollicular synapses. Successful completion of this project will provide the first circuit-level characterization of this important pathway and will lay the groundwork for a greater understanding of how top-down modulatory systems break down during disorders of communication.