Synergistic in vivo and in vitro approaches in the MSO

MSO 中的体内和体外协同方法

• 批准号: 8212018
• 负责人: Nace L Golding
• 金额: $ 19.82万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-07 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8212018
• 关键词: Acoustic Nerve; Acoustic Stimulation; Acoustics; Animals; Brain; Cell Nucleus; Cochlear Implants; Cochlear nucleus; Communication; Complex; Contralateral; Cues; Data; Detection; Development; Equilibrium; Hearing problem; In Vitro; Investigation; Ipsilateral; Measures; Medial; Methods; Modeling; Neurons; Noise; Olives - dietary; Physiological; Preparation; Process; Property; Role; Shapes; Signal Transduction; Slice; Solutions; Sound Localization; Speech; Speech Perception; Speech Sound; Stimulus; Synapses; Testing; Time; Whole-Cell Recordings; base; binaural hearing; deafness; extracellular; in vivo; interest; operation; patch clamp; public health relevance; research study; response; sound

DESCRIPTION (provided by applicant): The principal neurons of the medial superior olive (MSO) process interaural time differences (ITDs), cues used for localizing sounds along the horizontal plane as well as detection of speech and communication signals in noise. Despite intense interest in understanding the circuit dynamics that underlie ITD processing, there is surprisingly little experimental data available to drive current models of binaural hearing and MSO function. This is in part due to the fact that the biophysical specializations that are central to MSO neurons< functional role make these neurons unusually difficult to record in vivo with traditional extracellular recording methods. Although the advent of patch-clamp recordings from MSO neurons in brain slices has enabled detailed studies of the synaptic properties of MSO neurons, the obligatory disruption of circuit connections has precluded these studies from accurately reproducing the physiological timing and balance of binaural inputs. The current proposal will provide the first explicit effort to bridge the conceptual and technical gaps between cellular electrophysiological approaches in vitro and whole-animal acoustic investigations in vivo. First, we will employ patch-clamp recordings from MSO neurons in vivo and record responses to both monaural and binaural stimuli. We will use intracellular methods to compare the responses to ipsi- and contralateral acoustic stimulation in terms of their timing, shape, and (a) symmetry. We will test whether these monaural responses allow us to predict the binaural responses of the same neurons, which we will also measure. Second, in order to interpret in vivo experiments, we will develop a slice preparation containing the auditory nerve as well as the entire cochlear nucleus and superior olivary complex. By synchronously stimulating one or both auditory nerves during whole-cell recordings from MSO neurons, we will reproduce in vitro the natural timing of excitatory and inhibitory synaptic inputs, the details of which are the basis for all current models of binaural processing in the MSO. The impact and timing of inhibition will also be explored by comparing control responses to those evoked during pharmacological blockade of glycinergic inhibition. PUBLIC HEALTH RELEVANCE: Binaural cues are critical for speech perception and sound localization, and in recent years have become critical components of stimulation paradigms in auditory prostheses. An understanding of how binaural cues are processed by the brain is thus a prerequisite for the development of effective solutions for deafness and other hearing disorders.

描述（由申请人提供）：中间上橄榄（MSO）过程的主要神经元（MSO）过程跨时间差（ITD），用于沿水平平面定位声音的线索以及在噪声中检测语音和通信信号的检测。尽管对理解ITD处理基础的电路动力学的浓厚兴趣，但令人惊讶的是，几乎没有实验数据可用于驱动当前的双耳听力和MSO功能模型。这部分是由于以下事实：MSO神经元<功能作用的生物物理专长使这些神经元异常难以通过传统的细胞外记录方法在体内记录。尽管从大脑切片中MSO神经元的斑块钳记录的出现已经实现了对MSO神经元突触特性的详细研究，但电路连接的强制性破坏使这些研究无法准确地重现双肌输入的生理时机和平衡。当前的提案将提供第一个明确的努力，以弥合体内细胞电生理学方法之间的概念和技术差距。首先，我们将采用体内MSO神经元的斑块钳记录，并记录对单膜和双耳刺激的响应。我们将使用细胞内方法来比较其时间，形状和（a）对称性的ipsi和对侧声学刺激的反应。我们将测试这些单膜反应是否使我们能够预测同一神经元的双耳反应，我们还将测量。其次，为了解释体内实验，我们将开发包含听觉神经以及整个耳蜗核和上橄榄型复合物的切片制剂。通过在MSO神经元的全细胞记录中同步刺激一条或两只听觉神经，我们将在体外繁殖兴奋性和抑制性突触输入的自然时机，这些细节是MSO中所有双膜处理模型的基础。还将通过将控制反应与在甘氨酸能抑制剂的药理学阻断期间诱发的反应进行比较，从而探索抑制的影响和时机。 公共卫生相关性：双耳线索对于语音感知和声音本地化至关重要，近年来已成为听觉假体刺激范式的关键组成部分。因此，了解大脑如何处理双耳线索是开发有效解决方案和其他听力障碍解决方案的先决条件。