NEURONS AND CIRCUITS OF PERIOLIVARY NUCLEI

描述(申请人提供)：下丘(IC)是几乎所有上行和下行听觉通路整合的主要部位，IC神经元的许多基本特征由其抑制性输入深刻地塑造。GABA能抑制IC的一个重要来源是由斜方体内侧核(MNTB)和邻近的上橄榄旁核(SPON)组成的脑干环路。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电路提取并编码听觉刺激的间断，该电路的输出有助于IC中的时间处理。本应用的目的是：i)确定MNTB和SPON神经元如何整合它们的突触输入以产生该回路的输出；以及ii)检测MNTB/SPON回路的传出投射对IC神经元的反应特性的影响。提出了三个具体目标，每个目标都集中在从MNTB到IC的路径上的特定步骤。具体目标1将直接研究MNTB/SPON回路对中脑声音处理的影响，主要集中在IC神经元检测音调间隙的能力，并同步它们对正弦调幅音调的反应。一种双重记录配置将用于可逆地灭活Spon神经元，同时从其在IC中的突触后目标进行记录。在目标2和目标3中，我们将进行活体记录研究，以阐明抑制和兴奋在塑造SPON和MNTB神经元对刺激中断的反应特性中的作用。将采用多步骤、顺序的方案来系统地阻断特定的神经递质系统，以揭示它们作为一个整体对单个单位反应的单独贡献。将对每个记录的单元格进行全面的表征。在言语知觉中，密切放置的声音或声音成分之间的刺激间断的敏锐度在言语知觉中起着重要作用，而时间加工的缺陷与语言损伤有关。因此，在动物模型中更好地理解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了解。在以交流为基础的人类文化中，听力损失和由此导致的语言缺陷会带来社会和经济上的不利影响，并对生活质量产生巨大影响。这项研究的重点是哺乳动物脑干的一个重要的神经回路，其拟议的功能是检测听觉信号中的短暂中断；对这种中断或间隙进行适当的编码对人类的语音理解尤为重要。对时间结构的神经表示的知识，如间隙，将有助于最近引入的听觉中脑植入物的继续发展，以取代丧失的听神经功能。

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.