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

项目摘要/摘要 我们自己的运动导致感觉受体激活的模式可能与那些 由外部事件引起的。大脑是如何区分自我和他人的呢？ 长期存在的理论表明，本体感觉反馈或运动指令的内部副本，称为 随之而来的放电，可以用来预测和抵消由于动物自己的运动而产生的感觉输入。 然而，很难理解这样的过程实际上是在哪里以及如何在 大脑。一些最清晰的见解来自小脑样感觉结构， 鱼的电感官处理。在包括PI在内的这些系统中的研究表明，突触 可塑性对运动推论放电和本体感觉信息的预测和抵消作用 与鱼自身行为相关的自我产生的电感觉输入。这项提议试图理解 哺乳动物的大脑中是否也存在类似的机制。具体地说，我们将重点放在背侧耳蜗处 核(DCN)--哺乳动物听觉处理初期的一种结构，与 鱼类小脑样结构的环路和突触可塑性规则。我们将在活体内使用 从清醒、行为正常的小鼠进行录音，以测试DCN功能的非听觉、运动相关输入 来预测和取消与舔舔行为相关的自我产生的声音。拟议的研究是 预计将提供对DCN执行的计算的基本见解，包括对 长期以来的问题是，为什么哺乳动物听觉处理的第一阶段的电路类似于 在小脑中。更广泛地说，这项工作将提供对哺乳动物大脑如何 区分感官输入的自身来源和外部来源。最后，共同之处和一些 耳鸣--在没有外部声音的情况下持续感觉声音的衰弱情况 来源-与DCN神经元的过度活动有关，并被假设为部分原因是异常 DCN的突触可塑性和躯体感觉整合。这个项目试图理解正常的功能 DCN的突触可塑性和躯体感觉整合的研究，因此也可能为深入了解 耳鸣的病理生理学。

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.