Mechanisms that underlie cross-modal sensory plasticity

跨模式感觉可塑性的机制

• 批准号: 9764513
• 负责人: BING YE
• 金额: $ 32.92万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9764513
• 关键词: Animals; Behavior; Behavioral; Childhood; Clinical; Complement; Complex; Cues; Defect; Development; Disease; Drosophila genus; Financial compensation; Future; Genes; Genetic; Genetic Screening; Glucose; Habitats; Imaging Techniques; Individual; Individual Differences; Interneurons; Knowledge; Larva; Mission; Modality; Modeling; Molecular; Molecular Genetics; Neurodevelopmental Disorder; Neurons; Nociception; Nociceptors; Output; Patch-Clamp Techniques; Pathogenesis; Pathway interactions; Perception; Play; Preparation; Process; Public Health; Research; Role; Sensory; Sensory Deprivation; Signal Transduction; Somatosensory Cortex; Stimulus; Symptoms; Synapses; Synaptic Transmission; Synaptic plasticity; System; Tactile; Techniques; Testing; United States National Institutes of Health; V1 neuron; Vision; Visually Impaired Persons; area striata; behavioral plasticity; developmental plasticity; experience; gene function; genetic analysis; genetic approach; genome editing; improved; innovation; insight; mature animal; molecular modeling; multidisciplinary; multimodality; multisensory; nervous system disorder; neural circuit; neuroregulation; neurotransmitter release; new technology; novel; recruit; sensory stimulus; sensory system; somatosensory; spatiotemporal; synaptic inhibition; transmission process; ubiquitin ligase

Sensory experiences during development profoundly influence sensory processing in mature animals. Since most of an animal’s sensory experiences are multimodal, the activity of one sensory modality often causes long-term changes in another modality. Such cross-modal plasticity not only leads to compensation for sensory functions in the case of sensory deprivation, but also allows normal individuals to respond properly to sensory stimuli in their unique habitats or situations and contributes to individual’s differences in the perception of multisensory cues. Despite the importance of cross-modal plasticity, the underlying circuit and molecular mechanisms are poorly understood. In the proposed research, a novel form of cross-modal plasticity has been discovered in Drosophila and developed into a system for studying the underlying mechanisms at the behavioral, circuit, synaptic, and molecular levels. This system allows for comparison of cross-modal and modality-specific plasticity in the same sensory system. A genetic screen has identified novel regulators of cross-modal plasticity. The objective of the proposed research is to identify the mechanisms that underlie cross-modal plasticity in the developing somatosensory system of Drosophila larvae, and provide circuit and molecular models for guiding future studies in other species. The central hypothesis is that gentle mechanosensory inputs during development strengthen serotonergic inhibition of the synaptic transmission from nociceptors to multisensory second-order neurons (MSONs), which is achieved through specific genes in the MSONs. This hypothesis will be tested by identifying the circuit (Aim 1) and molecular (Aim 2) mechanisms that underlie cross-modal plasticity. The proposed research is innovative because it proposes the novel concept of distinct mechanisms that underlie cross-modal and modality-specific plasticity and will use a novel system that is amenable to the use of genetic screens to study cross-modal plasticity. This research is significant because it is expected to: 1) elucidate how cross- modal and modality-specific plasticity co-exist in a developing sensory system and demonstrate the role of neuromodulatory interneurons in establishing cross-modal plasticity during development; 2) identify a novel molecular mechanism that underlies cross-modal plasticity, particularly one that distinguishes it from modality-specific plasticity within the same neural circuit; 3) yield a multidisciplinary, state-of-the-art experimental system for identifying the principles that govern the experience--dependent assembly of neural circuits for multisensory integration. Moreover, because a common problem of many neurodevelopmental disorders is dysregulated multisensory integration, the proposed study will offer insights into the pathogenesis of these disorders.

发育过程中的感觉经验深刻地影响着成熟动物的感觉加工。以来 大多数动物的感觉经验是多模态的，一种感觉模态的活动往往会导致 另一种模式的长期变化。这种跨模态塑性不仅导致补偿 在感觉剥夺的情况下的感觉功能，但也允许正常人作出适当的反应， 在其独特的栖息地或情况下，对感官刺激的反应，并有助于个体在 对多感官线索的感知尽管跨模态可塑性的重要性，潜在的电路和 分子机制知之甚少。在所提出的研究中，一种新的形式的跨模态 在果蝇中发现了可塑性，并发展成为一个研究潜在的 在行为、电路、突触和分子水平上的机制。该系统允许比较 跨模态和特定模态的可塑性在同一感觉系统。一项基因筛查发现 新的跨模态可塑性调节器。拟议研究的目的是确定 果蝇躯体感觉系统发育中的跨模态可塑性机制 幼虫，并为指导其他物种的未来研究提供电路和分子模型。中央 一种假说认为，在发育过程中温和机械感觉输入加强了 从伤害感受器到多感觉二级神经元（MSONs）的突触传递， 通过MSON中的特定基因实现。将通过识别电路（目标）来检验此假设 1)和分子（目标2）机制，跨模态可塑性的基础。拟议的研究是 创新，因为它提出了独特的机制，跨模态和 模态特定的可塑性，并将使用一种新的系统，这是适合使用遗传筛选， 研究跨模态塑性。本研究具有重要意义，因为它有望：1）阐明如何交叉- 模态和模态特异性可塑性共存于发育中的感觉系统中，并证明了 神经调节中间神经元在建立跨模态可塑性在发展过程中; 2）确定一个新的 跨模态可塑性的分子机制，特别是区别于 同一神经回路内的模态特异性可塑性; 3）产生多学科的，最先进的 用于识别支配依赖于经验的神经元组装的原理的实验系统 多感官整合电路。此外，由于许多神经发育的共同问题， 疾病是失调的多感觉整合，拟议的研究将提供深入了解 这些疾病的发病机制。