Neural mechanisms of sound intensity coding

项目摘要。 对听力的神经生理学基础的详细了解是 对人类听力障碍的认识和对MOST进一步发展的指导 到目前为止成功的人工干预，人工耳蜗术。然而，我们仍然缺乏一个完整的描述 声音信息是如何在中枢神经系统的第一个中继器--耳蜗核--处理的。 我们在鸟类模型系统中的实验集中在第一个中枢神经系统靶点 听神经，耳蜗角状核，它启动了参与 使用双耳声级提示和频谱时间处理的定位。 快速适应是复杂声音和场景的神经编码的关键，通过实现 时间滤波、动态范围自适应和生成噪声不变信号表示。 当听神经元调整其放电率水平编码时，发生动态范围适应 根据声音刺激的统计数据，向上移动的声音分布更响亮。 适应性细胞过程，如短期突触可塑性(活动依赖的改变 突触重量)、固有放电率适应(通过离子通道失活或超极化电流)， 和通过第二信使系统的调制发射机反馈都是候选机制 实施强度相关适应。使用体外生理学、建模和体内实验的组合 ，我们将研究一种称为阈值适应的内在机制及其对 钠通道的失活。我们还检验了这样一种假设，即短期突触可塑性 为解决“动态范围问题”做出了贡献：人类如何跨越强度的多个数量级听到声音 在考虑到(以前已知的)有限的神经生理范围的情况下，行为实验的大小 纤维。 鉴于最近在使用假体设备恢复听力方面的进展，这些假体设备可以刺激 对于听觉神经，了解中枢神经系统如何解释神经活动是至关重要的。 这项研究将提供有关听觉信息如何从听神经传递到 第一中继器在听力正常的情况下，从而可以为耳蜗器等装置提供参考 直接刺激神经的植入物。对时间包络编码的强调还可以提供 关于可能与时间加工中断有关的障碍的新信息，如与年龄相关的 听力损失或听神经病，这可能会导致常见的但致残的 在噪音中理解语音。

Project Summary. A detailed understanding of the neurophysiological basis of hearing is fundamental to the understanding of human hearing impairment and the guidance of further development of the most successful prosthetic intervention to date, the cochlear implant. Yet we still lack a complete description of how sound information is processed at even the first central nervous system relay, the cochlear nucleus. Our experiments in the avian model system focus on the first central nervous system target of the auditory nerve, the cochlear nucleus angularis, which initiates the ascending pathways involved in localization using binaural sound level cues and spectrotemporal processing. Rapid adaptation is crucial for neural coding of complex sounds and scenes by implementing temporal filtering, dynamic range adaptation and generating noise-invariant signal representations. Dynamic range adaptation occurs when auditory neurons adjust their firing rate-level encoding depending on the statistics of the acoustic stimulation, shifting upward with louder sound distributions. Adaptive cellular processes such as short-term synaptic plasticity (activity-dependent alterations in synaptic weight), intrinsic firing rate adaptation (via ion channel inactivation or hyperpolarizing currents), and modulatory transmitter feedback via second messenger systems are all candidate mechanism for implementing intensity-related adaptation. Using a combination of in vitro physiology, modeling and in vivo recordings, we will investigate an intrinsic mechanism called threshold adaptation and its reliance on the inactivation of sodium channels. We also test the hypothesis that short-term synaptic plasticity contributes to solving the `dynamic range problem': how human can hear across many orders of intensity magnitude in behavioral experiments given the (formerly known) limited physiological range of nerve fibers. Given the recent advances in the restoration of hearing using prosthetic devices that stimulate the auditory nerve, it is critical to understand how nerve activity is interpreted by the central nervous system. This research will provide new data on how acoustic information is transmitted from the auditory nerve to the first central relay in normal hearing, and thus can provide a reference for devices such as cochlear implants that stimulate the nerve directly. The emphasis on temporal envelope coding may also provide new information on disorders that may be related to disrupted temporal processing, such as age-related hearing loss or auditory neuropathy, which can lead to a common but disabling difficulty with understanding speech in noise.