Neural Mechanisms of sound intensity coding

描述(申请人提供)：对听力的神经生理学基础的详细了解是理解人类听力损伤的基础，并指导迄今为止最成功的假体干预的进一步发展，即人工耳蜗术。然而，我们仍然缺乏一个完整的描述，即使是在第一个中枢神经系统继电器--耳蜗核--声音信息是如何处理的。声音的不同方面从听觉神经棘波序列中提取出来，并通过平行的神经通路进行编码。虽然时间线索的编码已经得到了广泛的研究，但强度线索的加工仍然不清楚，特别是与声音识别等非本地化任务有关的加工。我们最近确定，耳蜗核中的计时和强度回路是通过不同形式的短期突触可塑性的表达来区分的。体外研究表明，强度通路表现出短期促进和抑制的混合，允许传输速率编码的强度信息。相比之下，在计时电路中发现的短期抑制产生了突触增益控制，这有助于对计时线索进行强度不变的编码。我们将强度编码的研究扩展到响应动态调幅声音的尖峰序列，这是声音通信信号的重要组成部分。这项建议的目标是确定有助于声音强度编码的突触和细胞机制，并确定它们在完整大脑中的重要性。目的1采用鸡(禽)耳蜗核切片制备方法，探讨突触增强的两种机制：突触短时易化和NMDA受体电流对突触整合的贡献。我们使用动态钳位技术来确定耳蜗核神经元的输入输出功能。目的2通过电刺激和动态钳夹技术，测量耳蜗核听神经突触对频率调制棘波输入的生理反应，研究动态刺激如调幅声音是如何在耳蜗核的听神经突触中被处理的。在目标3中，我们将把我们的体外短期可塑性结果扩展到完整的耳蜗核，并在活体内对鸟类脑干进行细胞内记录。鉴于最近在使用刺激听神经的假体设备恢复听力方面的进展，了解中枢神经系统如何解释神经活动是至关重要的。这项建议将提供有关听觉信息转换的新信息，这将有助于改进辅助听力设备，并导致对正常听力的更好理解。

DESCRIPTION (provided by applicant): 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. Different aspects of sound are extracted from the auditory nerve spike trains and encoded via parallel neural pathways. While the coding of timing cues have been studied extensively, the processing of intensity cues remains unclear, especially relating to non-localization tasks such as sound recognition. We recently determined that the timing and intensity circuits in the cochlear nucleus are distinguished by the expression of different forms of short-term synaptic plasticity. In vitro studies have demonstrated that the intensity pathways exhibit a mixture of short-term facilitation and depression that allows the transmission of rate-encoded intensity information. In contrast, the short-term depression found in timing circuits creates a synaptic gain control that contributes to intensity-invariant coding of timing cues. We expand our investigation of intensity coding to spike trains in response to dynamic, amplitude modulated sounds, an important component of sound communication signals. The goal of this proposal is to identify the synaptic and cellular mechanisms that contribute to the encoding of sound intensity and establish their importance in the intact brain. Aim 1 uses the avian (chick) cochlear nucleus slice preparation to investigate two synaptic enhancement mechanisms: short-term synaptic facilitation and the contribution of NMDA-receptor currents to synaptic integration. We use dynamic clamp to determine the input-output function of cochlear nucleus neurons. Aim 2 investigates how dynamic stimuli like amplitude-modulated sounds are processed at auditory nerve synapses in the cochlear nucleus by measuring physiological synaptic responses to rate-modulated spike train inputs, using electrical stimulation and dynamic clamp. In Aim 3, we will extend our in vitro short-term plasticity results to the intact cochlear nucleus with in vivo, intracellular recordings in the avian brainstem. 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 proposal will provide new information on the transformation of auditory information which will help improve assisted-hearing devices and lead to a better understanding of normal hearing.