Mechanisms that underlie cross-modal sensory plasticity

跨模式感觉可塑性的机制

• 批准号: 10200909
• 负责人: BING YE
• 金额: $ 32.8万
• 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/10200909
• 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.

发育过程中的感觉体验深刻影响成熟动物的感觉处理。自从 动物的大多数感觉体验都是多模式的，一种感官方式的活动通常是原因 另一种方式的长期变化。这种跨模式的可塑性不仅会导致补偿 在感官剥夺的情况下，感觉功能，但也允许普通个人做出正确的反应 在其独特的栖息地或情况下进行感官刺激，并有助于个人在 多感官提示的感知。尽管具有跨模式可塑性的重要性，但基础电路和 分子机制知之甚少。在拟议的研究中，一种新型的跨模式形式 在果蝇中发现了可塑性，并发展为研究基础的系统 行为，电路，突触和分子水平的机制。该系统可以比较 在同一感觉系统中的跨模式和模式特异性可塑性。遗传屏幕已确定 跨模塑性的新型调节剂。拟议研究的目的是确定 果蝇发展中的体感系统中跨模式可塑性的基础的机制 幼虫，并提供电路和分子模型，用于指导其他物种的未来研究。中央 假设是发育过程中温和的机制输入更强的血清能抑制 从伤害感受器到多感觉二阶神经元（MSON）的突触传播， 通过MSON中的特定基因实现。该假设将通过识别电路进行检验（AIM 1）和分子（目标2）机制，这些机制是跨模式可塑性的基础。拟议的研究是 创新性，因为它提出了跨模式和跨模式的不同机制的新颖概念 特定于模态的可塑性，并将使用一个新型系统，该系统适合使用遗传筛选 研究跨模式可塑性。这项研究很重要，因为它有望：1）阐明如何交叉 模态和模态特异性可塑性在发展中的感觉系统中共存，并证明了 神经调节性中间神经元在发育过程中建立跨模式可塑性； 2）识别小说 分子机制是基于跨模式可塑性的基础，尤其是将其与众不同的分子机制 同一神经回路内的模式特异性可塑性； 3）产生多学科的最先进 实验系统，用于识别控制经验依赖于神经元的经验的原理 多感觉集成的电路。而且，因为许多神经发育的常见问题 疾病是多敏整合的失调，拟议的研究将提供有关该研究的见解。 这些疾病的发病机理。