Cellular Mechanisms of Auditory Information Processing

描述（由申请人提供）：听觉环境的中央处理开始于在大脑第一听觉中心，即耳蜗核的水平上产生多种平行的信息流处理。这些流是由具有不同突触输入和投射模式的神经元群产生的。为了完成它们的特定功能，每个流中的神经元利用不同的细胞机制，包括控制内在兴奋性的离子通道和目标依赖的突触输入。最近的研究表明，抑制在塑造腹侧耳蜗核（VCN）神经元对声音的反应中起着比以前认为的更重要的作用。抑制可以增强声音属性的频谱和时间处理，这对声音识别和定位以及语音处理都很重要。我们的研究表明，即使来自单一来源，两种主要细胞类型，毛状细胞和星状细胞的抑制时间过程是不同的。本研究的第一个目的是阐明VCN中两个局部抑制性突触回路的功能性突触组织。第二个目的是验证不同细胞类型上的突触电流是由不同的甘氨酸受体亚基介导的假设。我们还将研究在持续活动期间调节释放时间过程的突触前机制。第三个目标是将这些信息纳入详细的计算模型，该模型将用于探索VCN中时间和光谱处理中抑制的不同方面的重要性。第四个目标是确定这些抑制回路的功能如何受到听力损失的影响。所有这些实验都将在成年小鼠的大脑切片中进行。总的来说，我们的研究将确定早期听觉信息处理的关键机制，并确定这些机制如何有助于分析复杂的声音。然后，我们将确定这些机制如何受到听力损失的影响，这将为听力困难和人工耳蜗使用者的替代刺激策略提供见解。大脑中感觉处理的神经机制是我们正常感知能力的基础，包括识别声源和通过声音进行交流的能力。这些机制被感觉器官的损伤改变，因此，剩余的感知能力往往受到不利影响。在这个项目中，我们试图了解功能突触组织和潜在的机制，有助于听力在听觉通路的早期阶段。我们还将确定这些基本机制如何受到听力损失的影响，以及听力损失如何影响大脑中的高阶感觉处理。这些实验将最终为听力困难和人工耳蜗使用者提供替代刺激策略的见解。

DESCRIPTION (provided by applicant): Central processing of the auditory environment begins with the generation of diverse, parallel, streams of information processing at the level of the first auditory center of the brain, the cochlear nucleus. These streams are created by populations of neurons with distinct patterns of synaptic inputs and projections. In order to accomplish their specific functions, the neurons in each stream utilize different cellular mechanisms, including ion channels that govern intrinsic excitability, and target-dependent synaptic inputs. Recent studies have shown that inhibition plays a much more important role in sculpting the responses of ventral cochlear nucleus (VCN) neurons to sound than previously appreciated. Inhibition can serve to enhance both the spectral and temporal processing of sound attributes that are important for sound identification and localization as well as speech processing. Our studies have revealed that the time course of inhibition, even from a single source, is different in the two principal cell types, the bushy and stellate cells. The first aim of this proposal is to clarify the functional synaptic organization of two local inhibitory synaptic circuits in the VCN. The second aim is to test the hypothesis that the synaptic currents on different cell types are mediated by different glycine receptor subunits. We will also investigate the presynaptic mechanisms that regulate the time course of release during sustained activity. The third aim is to incorporate this information into a detailed computational model, which will be used to explore the importance of different aspects of inhibition in temporal and spectral processing in the VCN. The fourth aim is to determine how the function of these inhibitory circuits is affected by hearing loss. All of these experiments will be performed in brain slices of adult mice. Overall, our studies will identify critical mechanisms in early auditory information processing, and determine how those mechanisms contribute to the analysis of complex sounds. We will then determine how these mechanisms are affected by hearing loss, which will provide insights for alternative stimulation strategies for the hard-of-hearing and for cochlear implant users. The neural mechanisms of sensory processing in the brain underlie our normal perceptual abilities, including the identification of sound sources and the ability to communicate through sound. These mechanisms are changed by damage to the sensory organs, and consequently, residual perceptual abilities are often adversely affected. In this project, we seek to understand the functional synaptic organization and the underlying mechanisms that contribute to hearing at early stages of the auditory pathway. We will also determine how these basic mechanisms are affected by hearing loss, and how hearing loss affects higher-order sensory processing in the brain. These experiments will ultimately generate insights for alternative stimulation strategies for the hard-of-hearing, and for cochlear implant users.