Mechanisms for cancelling self-generated sounds in the mouse dorsal cochlear nucleus

消除小鼠耳蜗背核中自生声音的机制

• 批准号: 9280918
• 负责人: Nathaniel Sawtell
• 金额: $ 34万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9280918
• 关键词: Ablation; Acoustic Nerve; Affect; Animals; Auditory; Auditory system; Behavior; Behavioral; Brain; Brain Stem; Cells; Cerebellum; Cochlear nucleus; Data; Dorsal; Electrophysiology (science); Event; Feedback; Fiber; Fishes; Functional disorder; Generations; Hearing; Hyperactive behavior; Image; Injection of therapeutic agent; Interneurons; Link; Mediating; Motor; Movement; Mus; Nerve Fibers; Nervous system structure; Neurons; Noise; Output; Pattern; Perception; Positioning Attribute; Process; Receptor Activation; Research; Role; Sensory; Sensory Receptors; Signal Transduction; Site; Source; Structure; Structure of trigeminal nerve spinal tract nucleus; Synaptic plasticity; System; Testing; Tinnitus; Toxin; Trigeminal System; Viral; Work; auditory processing; awake; base; cognitive function; dorsal cochlear nucleus; experimental study; granule cell; imaging study; in vivo; insight; mossy fiber; neural circuit; neuromechanism; postsynaptic; relating to nervous system; response; sensory input; sensory stimulus; somatosensory; sound; synaptic function; theories

Project Summary/Abstract Our own movements result in patterns of sensory receptor activation that may be similar or identical to those caused by external events. How does the brain make the critical distinction between self and other? Longstanding theories suggest that proprioceptive feedback or internal copies of motor commands, known as corollary discharge, could serve to predict and cancel out sensory input due to an animal’s own movements. However, it has been difficult to understand where and how such a process actually takes place within the brain. Some of the clearest insights come from cerebellum-like sensory structures associated with electrosensory processing in fish. Work in these systems, including that of the PI, has shown that synaptic plasticity acting on motor corollary discharge and proprioceptive information functions to predict and cancel out self-generated electrosensory inputs related to the fish’s own behavior. This proposal seeks to understand whether similar mechanisms are at work in the mammalian brain. Specifically, we focus on the dorsal cochlear nucleus (DCN)--a structure at the initial stage of mammalian auditory processing which strikingly resembles cerebellum-like structures in fish in terms of its circuitry and synaptic plasticity rules. We will use in vivo recordings from awake, behaving mice to test whether non-auditory, movement-related input to DCN functions to predict and cancel self-generated sounds associated with licking behavior. The proposed research is expected to provide fundamental insight into the computations performed by the DCN, including an answer to the longstanding question of why circuitry at the first stage of mammalian auditory processing resembles that of the cerebellum. More generally, this work will provide mechanistic insights into how the mammalian brain distinguishes between self-generated and external sources of sensory input. Finally, the common and in some cases debilitating condition of tinnitus—the persistent perception of sound in the absence of an external sound source—is associated with hyperactivity in DCN neurons and is hypothesized to be due, in part, to aberrant synaptic plasticity and somatosensory integration in DCN. This project seeks to understand the normal function of synaptic plasticity and somatosensory integration in DCN and hence may also provide insights into the pathophysiology of tinnitus.

项目总结/摘要 我们自己的运动导致的感觉受体激活模式可能与那些类似或相同 由外部事件引起的。大脑如何区分自我和他人？ 长期以来的理论表明，本体感受反馈或运动命令的内部副本，称为 因此，放电可以用来预测和抵消由于动物自身运动引起的感觉输入。 然而，很难理解这样一个过程实际上是在哪里以及如何发生的。 个脑袋一些最清晰的见解来自小脑样感觉结构， 鱼类的电感觉处理。在这些系统中的工作，包括PI的工作，已经表明突触 可塑性作用于运动的必然放电和本体感受信息的功能，以预测和抵消 与鱼自身行为相关的自我产生的电感觉输入。这一建议旨在了解 哺乳动物的大脑中是否存在类似的机制。具体来说，我们专注于背侧耳蜗 核（DCN）--哺乳动物听觉处理初始阶段的结构， 在神经回路和突触可塑性规则方面，鱼类的小脑样结构。我们将在体内使用 从清醒的，行为小鼠的记录，以测试是否非听觉，运动相关的输入到DCN功能 来预测和消除与舔行为相关的自发声音。拟议的研究是 预计将提供对DCN执行的计算的基本见解，包括以下问题的答案 为什么哺乳动物听觉处理的第一阶段的电路与 小脑。更一般地说，这项工作将提供机制的见解，如何哺乳动物的大脑 区分自我产生的和外部来源的感官输入。最后，在某些情况下， 例耳鸣的衰弱状态-在没有外部声音的情况下持续感知声音 来源-与DCN神经元的过度活跃有关，并假设部分是由于异常的 DCN中突触可塑性和躯体感觉整合。本项目旨在了解正常功能 DCN的突触可塑性和体感整合，因此也可能提供深入了解 耳鸣的症状有哪些？