Neural Mechanisms of sound intensity coding

声强编码的神经机制

• 批准号: 8035389
• 负责人: KATRINA M MACLEOD
• 金额: $ 34.09万
• 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 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8035389
• 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. 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.

描述（由申请人提供）：对听力的神经生理基础的详细理解是对人类听力障碍的理解以及迄今为止最成功的假肢干预措施的进一步发展的指导。然而，我们仍然缺乏关于在第一个中央神经系统继电器（人工耳蜗核）如何处理声音信息的完整描述。声音的不同方面是从听觉神经尖峰列车中提取的，并通过平行的神经通路编码。尽管已经对定时提示的编码进行了广泛的研究，但强度线索的处理仍不清楚，尤其是与非定位任务（例如声音识别）有关。我们最近确定，人工耳蜗核中的时间和强度电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，强度途径表现出短期促进和抑郁症的混合物，允许速率编码的强度信息传播。相反，定时电路中发现的短期抑郁症会产生突触增益控制，从而有助于定时提示的强度不变编码。我们将对强度编码的调查扩展到尖峰列车，以响应动态，振幅调制声音，这是声音通信信号的重要组成部分。该建议的目的是确定有助于编码声音强度并确定其在完整大脑中的重要性的突触和细胞机制。 AIM 1使用禽（雏鸡）耳蜗核切片制剂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。我们使用动态夹具确定耳蜗神经元的输入输出功能。 AIM 2研究了如何使用电刺激和动态夹具测量对速率调节的Spike Train输入的生理突触反应，如何通过测量对速率调节的Spike Train输入的生理突触反应来处理耳蜗核中听觉神经突触的动态刺激。在AIM 3中，我们将在体外，体内，细胞内记录中，将体外短期可塑性结果扩展到完整的耳蜗核。鉴于使用刺激听觉神经的假体设备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至关重要。该提案将提供有关听觉信息转换的新信息，这些信息将有助于改善辅助听证设备并更好地理解正常的听力。 公共卫生相关性：改进的人工耳蜗设备是听力研究的主要目标。我们的实验将通过定义听觉神经的电刺激如何转化为脑干目标，即耳蜗核的生理活性来进一步进一步。检查大脑如何编码声音强度的调节性还将为患者在嘈杂环境中理解语音的听力障碍和人工耳蜗所带来的困难提供新的见解。