Neural Mechanisms of sound intensity coding

描述（由申请人提供）：详细了解听力的神经生理基础是理解人类听力障碍的基础，也是迄今为止最成功的人工耳蜗干预的进一步发展的指导。然而，即使是第一个中枢神经系统中继——耳蜗核，声音信息是如何被处理的，我们仍然缺乏完整的描述。声音的不同方面是从听觉神经脉冲序列中提取出来的，并通过平行的神经通路进行编码。虽然时间线索的编码已被广泛研究，但强度线索的处理仍不清楚，特别是与声音识别等非定位任务有关。我们最近确定，耳蜗核的时间和强度电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，从而允许传输速率编码的强度信息。相比之下，在定时电路中发现的短期抑制产生了突触增益控制，有助于定时线索的强度不变编码。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。本研究的目标是确定参与声音强度编码的突触和细胞机制，并确定其在完整大脑中的重要性。目的1利用禽（鸡）耳蜗核切片制备研究两种突触增强机制：短期突触促进和nmda受体电流对突触整合的贡献。采用动态箝位法测定耳蜗核神经元的输入-输出函数。目的2研究动态刺激如振幅调制的声音是如何在耳蜗核听觉神经突触处理的，通过测量生理突触对速率调制尖峰串输入的反应，使用电刺激和动态钳。在Aim 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，并在体内记录鸟类脑干的细胞内。鉴于使用刺激听神经的假体装置恢复听力的最新进展，了解中枢神经系统如何解释神经活动是至关重要的。这一建议将提供关于听觉信息转换的新信息，这将有助于改进辅助听力设备，并使人们更好地了解正常听力。

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. PUBLIC HEALTH RELEVANCE: Improved cochlear implant devices are a major goal of hearing research. Our experiments will further this goal by defining how electrical stimulation of the auditory nerve translates into physiological activity in the brainstem target, the cochlear nucleus. Examination of how modulations of sound intensity are coded by the brain will also provide new insight into the difficulties that the hearing impaired and cochlear implant patients have in understanding speech in noisy environments.