Mechanisms of Synaptic Tuning Along the Tonotopic Map of Nucleus Laminaris

沿层状核音位图的突触调节机制

• 批准号: 8058272
• 负责人: Sriharsha Vemana
• 金额: $ 5.22万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-09 至 2012-08-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8058272
• 关键词: Accounting; Action Potentials; Attenuated; Auditory; Biological Models; Birds; Boxing; Brain; Brain Stem; Cell Nucleus; Cells; Characteristics; Chickens; Cochlear Implants; Cochlear nucleus; Complex; Computer software; Contralateral; Dendrites; Dependence; Development; Distal; Ear; Electric Stimulation; Event; Excitatory Postsynaptic Potentials; Foundations; Frequencies; Goals; Gray unit of radiation dose; Hearing; Height; Implant; In Vitro; Ipsilateral; Kinetics; Location; Maps; Measures; Medial; Methods; Modeling; Morphology; Music; Nature; Nerve Fibers; Neurons; Olives - dietary; Output; Patients; Phase; Physiological; Potassium Channel; Process; Property; Public Health; Relative (related person); Research; Research Personnel; Role; Sensory; Shapes; Signal Transduction; Simulate; Site; Slice; Source; Speech; Stimulus; Structure; Sucrose; Sum; Synapses; System; Testing; Time; Training; Travel; Variant; Width; Work; analog; attenuation; auditory pathway; base; channel blockers; data acquisition; design; excitatory neuron; falls; hearing impairment; hyperpolarization-activated cation channel; interest; neuronal cell body; patch clamp; postsynaptic; public health relevance; relating to nervous system; response; sound; sound frequency; theories; transmission process; voltage; voltage clamp

DESCRIPTION (provided by applicant): We study the mechanisms by which neurons encode sound location, using the chick auditory brain stem as a model system. This research has broad relevance to understanding how brain circuits extract behaviorally relevant information from sensory input. The project may also advance the long-term, health-related goal of developing cochlear implants that more effectively drive the brain circuits responsible for normal hearing. The proposed studies will investigate the neurons in Nucleus Laminaris (NL), which is the first site in the chicken's auditory pathway that receives signals from both ears and can detect the location of a sound source. Neurons in different parts of NL respond to different sound frequencies (called characteristic frequency, or CF). Previous studies have shown that neurons with different CF have different properties, and we believe that these differences tune the neurons to respond best to signals of a particular frequency. The input signals that excite NL neurons, known as excitatory postsynaptic currents (EPSCs), show large differences between NL neurons of different CF. Specifically, EPSCs in low-CF neurons are smaller and slower than those in high-CF cells. We believe that these differences are important for tuning NL neurons to different frequencies. The mechanisms underlying the differences in EPSCs are not known, but previous morphological studies of NL neurons suggest an interesting hypothesis. These studies showed that the dendrites of NL neurons, which are the structures that receive EPSCs, are much longer on low-CF cells than on high-CF cells. After arriving at a neuron, the EPSC must travel down the dendrite to the cell body in order to trigger an output response (the action potential). In other neurons, it is known that long dendrites reduce the size of the EPSC and slow it down by the time it reaches the cell body. This process is called dendritic filtering. We hypothesize that EPSCs in low-CF NL neurons are slower than those in high-CF cells because of dendritic filtering. We propose two specific aims to test this hypothesis. For both, we will record electrically from NL neurons in slices of the chick brainstem. In the first aim, we will elicit EPSCs by electrical stimulation of incoming nerve fibers. The amount of dendritic filtering will be measured based on the changes in the EPSC caused by changing the voltage of the cell body at different times. If the amount of dendritic filtering is large, we will have to change the voltage well before the EPSC in order to see an effect. In the second aim, we will use a different stimulus (concentrated sucrose) to elicit EPSCs on specific parts of the cell. If there is much dendritic filtering, EPSCs from the dendrites will be smaller and slower than those elicited at the cell body. Beyond its scientific value, this research will provide training in patch clamp recording, morphological studies of the recorded neurons, and computer programming and software applications for data acquisition and analysis. It is hoped that studies in this beautifully organized, well-characterized neural system will also encourage intellectual development, leading to proficiency as an independent investigator in the field. PUBLIC HEALTH RELEVANCE: While the proposed research is basic in nature, it may eventually contribute to public health by providing a more rational foundation for the design of cochlear implants. At present, cochlear implants are of great benefit to many patients with hearing loss but fall far short of restoring normal hearing, particularly for complex stimuli such as speech and music. A greater understanding of the response properties of neurons in brainstem auditory circuits may aid in the design of implants that produce output signals tailored to the properties of recipient neurons, allowing greater transmission of relevant sound information.

描述（由申请人提供）：我们研究神经元用鸡听觉脑干作为模型系统编码声音位置的机制。这项研究与理解大脑电路如何从感觉输入中提取与行为相关的信息具有广泛的相关性。该项目还可以推进长期，健康相关的目标，即开发人工耳蜗，以更有效地推动负责正常听力的大脑电路。拟议的研究将研究laminaris核（NL）中的神经元，该神经元是鸡的听觉途径中的第一个位点，从两只耳朵接收信号并可以检测声源的位置。 NL不同部位的神经元对不同的声音频率（称为特征频率或CF）响应。先前的研究表明，具有不同CF的神经元具有不同的特性，我们认为这些差异调节神经元对特定频率信号的反应最佳。 激发NL神经元（称为兴奋性突触后电流（EPSC））的输入信号显示出不同CF的NL神经元之间的巨大差异。具体而言，低CF神经元中的EPSC比高CF细胞中的EPSC小且较慢。我们认为，这些差异对于将NL神经元调整到不同频率很重要。 EPSC差异的基础机制尚不清楚，但是NL神经元的先前形态学研究表明了一个有趣的假设。这些研究表明，在低CF细胞上，NL神经元的树突比在高CF细胞上长得多。到达神经元后，EPSC必须向下沿树突传播到细胞体，以触发输出响应（动作电位）。在其他神经元中，众所周知，长长的树突减少EPSC的大小，并在其到达细胞体时减速。此过程称为树突过滤。 我们假设低CF NL神经元中的EPSC由于树突状滤波而在高CF细胞中的EPSC慢。我们提出了两个特定的目的来检验这一假设。对于这两者，我们都将从NL神经元中记录小鸡脑干的切片。在第一个目标中，我们将通过对传入神经纤维的电刺激引起EPSC。树突过滤的量将根据在不同时间改变细胞体电压引起的EPSC的变化来测量。如果树突过滤的量很大，我们将必须在EPSC之前及时更改电压，以查看效果。在第二个目标中，我们将使用不同的刺激（浓缩蔗糖）在细胞的特定部位引起EPSC。如果存在太多的树突过滤，则来自树突的EPSC比在细胞体中引起的epss较小且较慢。 除了其科学价值之外，这项研究还将提供有关斑块夹记录，记录神经元的形态学研究以及用于数据获取和分析的计算机编程和软件应用程序的培训。希望在这个精美的，良好的特征神经系统中的研究也将鼓励智力发展，从而熟练成为该领域的独立研究者。 公共卫生相关性：虽然拟议的研究本质上是基本的，但最终可能会通过为人工耳蜗设计提供更合理的基础来为公共卫生做出贡献。目前，耳蜗植入物对许多听力损失的患者具有很大的好处，但远远远远没有恢复正常的听力，尤其是对于诸如语音和音乐等复杂刺激而言。对脑干听觉电路中神经元的响应特性有更深入的了解可以帮助设计植入物，该植入物生成针对受体神经元特性的输出信号的设计，从而使相关声音信息更大。