Synaptic mechanisms in the auditory system

描述(由申请者提供)：我们的长期目标是了解神经回路如何支持听觉处理。在这里，我们将探索在耳蜗背核(DCN)的分子层和颗粒细胞区的突触通讯的动态方面，它们的神经调节和可塑性。这项研究的结果将揭示DCN电路元件的新方面，这些信息将为当前的听觉和多感觉处理画面增加新的维度。DCN在声源定位和各种非听觉信号的整合中发挥作用，潜在地用于头/耳定位或取消自产生的声音。人们还认为，DCN在耳鸣的维持中发挥了作用，耳鸣是一种广泛存在的令人不安的慢性临床疾病。DCN在较低的听觉通路中是独一无二的，表现出强大的突触可塑性--这不是听神经输入的可塑性，而是多感觉输入的可塑性，突显了后者必须具有的重要作用 在DCN功能中。这项提议研究了多感觉处理的两个连续阶段：首先是听觉颗粒细胞，然后是DCN分子层。所有的多感觉信息都通过苔藓纤维进入DCN，这些纤维终止于颗粒细胞的七个亚区。然而，这些颗粒区域的不同作用以及在每个区域中发生的不同形式的加工都是未知的。因此，我们将阐明颗粒细胞是如何转换信号的，以便理解后面电路中计算的意义。在分子层，颗粒细胞的平行纤维终止于梭形的主细胞和两个中间神经元，即侧轮。 浅层星状细胞(SSC)。在这里，我们将探索SSCs的一个意想不到的功能，即它们介导来自主细胞的反馈信号，从而促进分子层的活动。最后，我们将确定颗粒区域和分子层的处理如何受到强大的神经调节剂的控制。我们将使用电生理和光学方法，并产生在特定类型的DCN细胞中表达荧光团或通道视紫红质(ChR2)的新小鼠品系。

DESCRIPTION (provided by applicant): Our long-term goal is to understand how neural circuits support auditory processing. Here, we will explore dynamic aspects of synaptic communication, their neuromodulation and plasticity, in the molecular layer and granule cell regions of the dorsal cochlear nucleus (DCN). The results of this study will reveal novel aspects of DCN circuit elements, information which will add new dimensions to the current picture of auditory and multisensory processing. The DCN functions in sound source localization and the integration of a variety of non-auditory signals, potentially for head/ear orientation or cancelatin of self-generated sound. It is also believed that the DCN plays a role in the maintenance of tinnitus, a widespread and disturbingly chronic clinical condition. The DCN is unique in the lower auditory pathway for showing robust synaptic plasticity - this is plasticity not of the auditory nerve input but rather of multisensory input, highlighting the important role that latter must have in DCN function. This proposal examines two sequential stages of multisensory processing: first in auditory granule cells and then in the DCN molecular layer. All multisensory information enters the DCN through mossy fibers which terminate in seven sub regions of granule cells. Yet, the different roles of these granule regions and what distinct forms of processing occur in each are unknown. We will therefore clarify how granule cells transform signals in order to understand the significance of computations later in the circuit. In the molecular layer, parallel fibers of granule cells terminate onto fusiform principal cells and two interneurons, the cartwheel cell and the superficial stellate cell (SSC). Here we will explore an unexpected function for the SSCs, that they mediate feedback signaling from the principal cells that facilitates activity withi the molecular layer. Lastly, we will determine how processing in granule areas and the molecular layer is controlled by the potent neuromodulators. We will use electrophysiological and optical approaches, and generate new mouse lines in which fluorophores or channelrhodopsin (ChR2) are expressed in specific DCN cell types.