Adaptive Sensory Processing in the dorsal cochlear nucleus of the mouse

描述（由申请人提供）：耳蜗背核（DCN）在听觉处理的第一阶段包含一个小脑样回路。纺梭状细胞（FCs）将听觉神经传递的初级听觉信息与苔藓纤维-颗粒细胞-平行纤维系统传递的信息整合在一起。侧轮细胞（CWCs）是DCN中主要的抑制性中间神经元，也接受平行纤维输入，在形态、生理和基因表达模式上与浦肯野细胞非常相似。苔藓纤维输入DCN传递一系列非听觉信息，包括来自脊髓-三叉核、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，耳鸣是在没有外部声源的情况下对声音的感知。据报道，耳鸣患者能够通过下颌和颈部的运动来调节所感知声音的振幅和频率，这表明了这种病理中涉及的多感觉整合。为什么这种感觉整合发生在听觉处理的早期阶段，一直困扰着科学家。一个流行的假设来自于一个类似小脑的结构，它与弱电鱼的电感觉处理有关，即电感觉外侧叶（ELL）。通过其苔藓状纤维-颗粒细胞-平行纤维系统传递的信号被用作预测信号，以抵消鱼自身行为产生的电感觉信息，从而更好地处理来自环境的行为相关刺激。这些预测是由与ELL传出细胞平行的纤维突触的抗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。这个提议将测试DCN是否执行类似的功能，即预测和取消自我产生的感觉刺激。第一个目标

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.