Synaptic mechanisms in the auditory system

描述（由申请人提供）：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，我们将探讨突触通讯的动态方面，他们的神经调节和可塑性，在耳蜗背核（DCN）的分子层和颗粒细胞区域。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官处理图像增加新的维度。DCN在声源定位和各种非听觉信号的整合中起作用，可能用于头/耳定向或消除自产生的声音。人们还认为，DCN在耳鸣的维持中起作用，耳鸣是一种广泛而令人不安的慢性临床疾病。DCN在低听觉通路中表现出强大的突触可塑性是独一无二的——这种可塑性不是听觉神经输入的可塑性，而是多感觉输入的可塑性，突出了后者必须具有的重要作用

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.