Neural Mechanisms of sound intensity coding

声强编码的神经机制

• 批准号: 8610283
• 负责人: KATRINA M MACLEOD
• 金额: $ 35.74万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8610283
• 关键词: Acoustic Nerve; Acoustics; Address; Animals; Area; Auditory; Birds; Brain; Brain Stem; Characteristics; Cochlear Implants; Cochlear nucleus; Code; Communication; Cues; Development; Devices; Electric Stimulation; Elements; Environment; Exhibits; Goals; Hearing; Human; In Vitro; Intervention; Investigation; Knowledge; Lead; Link; Maintenance; Measures; Mediating; Mental Depression; N-Methyl-D-Aspartate Receptors; Nerve; Nerve Fibers; Neural Pathways; Neuraxis; Neurons; Neurophysiology - biologic function; Output; Pathway interactions; Patients; Pattern; Physiological; Preparation; Presynaptic Terminals; Process; Property; Prosthesis; Research; Role; Sensory Process; Signal Transduction; Slice; Sound Localization; Speech; Staging; Stimulus; Synapses; Synaptic plasticity; System; Testing; Time; Training; Translating; Work; auditory pathway; base; hearing impairment; implantable device; improved; in vivo; insight; neuromechanism; neurophysiology; novel; postsynaptic; presynaptic; public health relevance; relating to nervous system; research study; response; restoration; sound; transmission process

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.

描述（由申请人提供）：对听力的神经生理学基础的详细了解对于理解人类听力障碍以及指导进一步开发迄今为止最成功的假体干预措施（人工耳蜗）至关重要。然而，我们仍然缺乏对声音信息如何在第一个中枢神经系统中继站——耳蜗核——中进行处理的完整描述。声音的不同方面是从听觉神经棘突序列中提取的，并通过并行神经通路进行编码。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相关的处理。我们最近确定，耳蜗核中的时间和强度回路通过不同形式的短期突触可塑性的表达来区分。体外研究表明，强度路径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，时序电路中发现的短期抑制会产生突触增益控制，有助于时序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（声音通信信号的重要组成部分）的尖峰序列。该提案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。目标 1 使用禽类（鸡）耳蜗核切片制备来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。我们使用动态钳来确定耳蜗核神经元的输入输出函数。目标 2 通过使用电刺激和动态钳测量对速率调制尖峰序列输入的生理突触反应，研究如何在耳蜗核中的听觉神经突触处处理调幅声音等动态刺激。在目标 3 中，我们将通过禽类脑干的体内细胞内记录将体外短期可塑性结果扩展到完整的耳蜗核。鉴于最近使用刺激听觉神经的假肢装置恢复听力方面取得了进展，了解中枢神经系统如何解释神经活动至关重要。该提案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更好地理解正常听力。