Adaptive Sensory Processing in the dorsal cochlear nucleus of the mouse

小鼠耳蜗背核的自适应感觉处理

• 批准号: 8835175
• 负责人: Shobhit Singla
• 金额: $ 4.34万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8835175
• 关键词: Acoustic Nerve; Auditory; Behavior; Behavioral Mechanisms; Brain Stem; Brain region; Cavia; Cell Nucleus; Cells; Cerebellum; Data; Ear; Electric Fish; Environment; Event; Exhibits; External Ear; Felis catus; Fiber; Fishes; Frequencies; Fusiform Cell; Gene Expression Profile; Glutamates; Goals; Head; Hearing; Hyperactive behavior; Image; In Vitro; Interneurons; Lateral; Lead; Lobe; Loudness; Mammals; Molecular Genetics; Morphology; Motor; Movement; Mus; Nature; Neck; Neurons; Output; Pathology; Patients; Perception; Physiology; Pontine structure; Preparation; Process; Purkinje Cells; Rattus; Reporting; Research; Role; Scientist; Sensory; Sensory Process; Signal Transduction; Source; Speed; Staging; Stimulus; Structure; Structure of nucleus cuneatus; Structure of trigeminal nerve spinal tract nucleus; Synapses; Synaptic plasticity; System; Techniques; Testing; Time; Tinnitus; auditory stimulus; awake; base; dorsal cochlear nucleus; electrical microstimulation; external ear auricle; granule cell; in vivo; insight; jaw movement; lateral vestibular nucleus; microstimulation; mossy fiber; multisensory; public health relevance; research study; response; sensory integration; sensory stimulus; sensory system; somatosensory; sound; sound frequency; superior colliculus Corpora quadrigemina; tool

DESCRIPTION (provided by applicant): The dorsal cochlear nucleus (DCN) contains a cerebellum-like circuit in the first stage of auditory processing. Fusiform cells (FCs) integrate primary auditory information conveyed via the auditory nerve with information conveyed via mossy fiber-granule cell-parallel fiber system. Cartwheel cells (CWCs), a major inhibitory interneuron in the DCN also receiving parallel fiber input, closely resembles Purkinje cells in morphology, physiology, and pattern of gene expression. Mossy fiber input to DCN convey a range of non-auditory information including information from the spinal-trigeminal nucleus, the cuneate nucleus, the vestibular nucleus, the lateral reticular nucleus, and the pons. Aberrant plasticity in FCs has been implicated in tinnitus, the perception of a sound without the existence of an external sound source. Patients who have tinnitus have reported being able to modulate the amplitude and frequency of the perceived sound through movement of the jaw and neck demonstrating the multisensory integration involved in this pathology. Why such sensory integration occurs at so early a stage in auditory processing has long puzzled scientists. One prevailing hypothesis comes from evidence from a similar cerebellum-like structure involved in electrosensory processing in weakly electric fish, the electrosensory lateral lobe (ELL). Signals conveyed via its mossy fiber-granule cell-parallel fiber system are used as predictive signals to cancel electrosensory information generated by the fish's own behavior to better process behaviorally relevant stimuli from the environment. These predictions are generated by anti-Hebbian plasticity rules at parallel fiber synapses onto ELL efferent cells. Similar plasticity ruls are found at parallel fiber synapses in DCN. This proposal will test if the DCN performs a similar function, namely the prediction and cancellation of self-generated sensory stimuli. The first goal of this proposal is to first characterize DCN responses to non-auditory input, namely outer ear (pinna) movement in both anesthetized and awake mice. While there have been anatomical and electrophysiologic studies in a number of species including cats, guinea pigs, and rats, little is known about non-auditory input to DCN in mice. I will then test the hypothesis that these inputs are used as predictive signals to separate behaviorally relevant from self-generated sensory stimuli. These studies will provide the first insights into the function of the DCN and allow futur studies to use the powerful genetic and molecular techniques developed for mice to further study the roles of a cerebellum-like circuit in sensory processing.

描述(申请人提供)：耳蜗背核(DCN)在听觉处理的第一阶段包含一个小脑样回路。梭形细胞(FCS)整合了通过听神经传递的初级听觉信息和通过苔藓纤维-颗粒细胞-平行纤维系统传递的信息。车轮细胞(CWCS)是DCN中主要的抑制性中间神经元，也接受平行的纤维输入，在形态、生理和基因表达模式上与Purkinje细胞非常相似。苔藓纤维进入DCN传递一系列非听觉信息，包括来自三叉神经脊束核、楔状核、前庭核、外侧网状核和脑桥的信息。FCS的异常可塑性与耳鸣有关，耳鸣是指在没有外部声源存在的情况下感知声音。有耳鸣的患者报告能够通过颌骨和颈部的运动来调节感知声音的幅度和频率，这表明了这种病理涉及的多感觉整合。为什么这种感觉整合发生在听觉处理的这么早阶段，长期以来一直让科学家们感到困惑。一种流行的假说来自一种类似于小脑样结构的证据，该结构参与弱电鱼类的电感觉处理，即电感觉侧叶(ELL)。通过苔藓纤维-颗粒细胞-平行纤维系统传递的信号被用作预测信号，以抵消鱼类自身行为产生的电感觉信息，以更好地处理来自环境的行为相关刺激。这些预测是由平行纤维突触到ELL传出细胞的反Hebbian可塑性规则产生的。在DCN的平行纤维突触中也发现了类似的可塑性规律。这项提议将测试DCN是否执行类似的功能，即预测和消除自身产生的感觉刺激。第一个目标 这项建议的目的是首先描述DCN对非听觉输入的反应，即麻醉和清醒小鼠的外耳(耳廓)运动。虽然已经在包括猫、豚鼠和大鼠在内的许多物种中进行了解剖学和电生理学研究，但对小鼠DCN的非听觉输入知之甚少。然后，我将测试这样的假设，即这些输入被用作预测性信号，将行为相关的刺激与自身产生的感觉刺激分开。这些研究将提供对DCN功能的第一次洞察，并使未来的研究能够使用为小鼠开发的强大的遗传和分子技术来进一步研究小脑样回路在感觉处理中的作用。