NEURONS AND CIRCUITS OF PERIOLIVARY NUCLEI

描述（由申请人提供）：下丘（IC）是整合几乎所有上行和下行听觉通路的主要部位，IC神经元的许多基本特征都受到其抑制性输入的深刻影响。GABA能抑制IC的一个重要来源来自由斜方体内侧核（MNTB）和附近的上级橄榄旁核（SPON）形成的脑干回路。这项研究计划的长期目标是阐明MNTB/SPON回路在听力中的功能作用。我们的中心假设是，MNTB/SPON电路提取和编码听觉刺激的不连续性，并且该电路的输出有助于IC中的时间处理。本申请的目的是i）确定MNTB和SPON神经元如何整合它们的突触输入以生成该电路的输出，以及ii）检查MNTB/SPON电路的传出投射对IC神经元的响应特性的影响。提出了三个具体目标，每个目标侧重于从MNTB到IC的途径上的沿着具体步骤。具体目标1将直接检查MNTB/SPON回路对中脑声音处理的影响，主要关注IC神经元检测音调间隙的能力，以及同步它们对正弦幅度调制音调的反应。双记录配置将用于可逆地记录SPON神经元，同时记录IC中的突触后靶点。在目标2和3中，我们将进行体内记录研究，以阐明抑制和兴奋在塑造SPON和MNTB神经元对刺激不连续性的响应特性中的作用。一个多步骤的，顺序的协议将系统地阻止特定的神经递质系统，以揭示其作为一个整体的单个单位响应的个人贡献。将对每个记录的细胞进行全面表征。刺激不连续性的敏锐度检测之间的紧密放置的声音或声音的组件起着重要的作用，在言语知觉，和赤字的时间处理与语言障碍。因此，在动物模型中更好地了解MNTB/SPON回路的功能将促进我们对人类语音理解的神经基础的认识。在以沟通为基础的人类文化中，听力损失及其导致的语言缺陷会带来社会和经济上的不利因素，并对生活质量产生巨大影响。这项研究的重点是一个突出的神经回路的哺乳动物脑干，其拟议的功能是检测短中断的听觉信号，这种中断，或差距，适当的编码，是特别重要的人类语言理解。颞叶结构，如差距的神经表示的知识，将有助于最近推出的听觉中脑植入物，以取代失去的听觉神经功能的持续发展。

DESCRIPTION (provided by applicant): The inferior colliculus (IC) is a major site for integration of virtually all ascending and descending auditory pathways, and many fundamental characteristics of IC neurons are profoundly shaped by their inhibitory inputs. A significant source of GABAergic inhibition to the IC originates from a brainstem circuit formed by the medial nucleus of the trapezoid body (MNTB) and the nearby superior paraolivary nucleus (SPON). The long-term goal of this research program is to clarify the functional role of the MNTB/SPON circuit in hearing. Our central hypothesis is that the MNTB/SPON circuit extracts and encodes auditory stimulus discontinuities, and that the output of this circuit contributes to temporal processing in the IC. The objectives of this application are i) to determine how MNTB and SPON neurons integrate their synaptic inputs to generate the output of this circuit, and ii) to examine the impact of the MNTB/SPON circuit's efferent projection on response properties of IC neurons. Three Specific Aims, each focusing on a specific step along the pathway from the MNTB to the IC, are proposed. Specific Aim 1 will directly examine the influence exerted by the MNTB/SPON circuit on sound processing in the midbrain, focusing primarily on the ability of IC neurons to detect gaps in tones, and to synchronize their responses to sinusoidally amplitude modulated tones. A dual recording configuration will be used to reversibly inactivate SPON neurons, while simultaneously recording from their postsynaptic targets in the IC. In Aims 2 and 3, we will perform in-vivo recording studies to clarify the roles of inhibition and excitation in shaping the response properties of SPON and MNTB neurons to stimulus discontinuities. A multi-step, sequential protocol will be employed to systematically block specific neurotransmitter systems in order to reveal their individual contributions to single-unit responses as a whole. Comprehensive characterizations of each recorded cell will be performed. The acuity with which stimulus discontinuities are detected between closely placed sounds or components of sounds plays an important role in speech perception, and deficits in temporal processing are related to language impairment. Therefore, a better understanding of the function of the MNTB/SPON circuit in animal models will advance our knowledge of the neural basis for human speech comprehension. In the communication-based culture of humans, hearing loss and the resulting deficiencies in language confer social and economic disadvantages, and have tremendous impact on the quality of life. This research focuses on a prominent neural circuit of the mammalian brainstem, whose proposed function is to detect short interruptions in auditory signals; the proper encoding of such interruptions, or gaps, is particularly important for human speech comprehension. Knowledge of the neural representation of temporal structures, such as gaps, will contribute to the continued development of recently introduced auditory midbrain implants that substitute for lost auditory nerve function.