Mechanisms that underlie cross-modal sensory plasticity

发育过程中的感觉体验深刻地影响着成熟动物的感觉加工。自.以来 大多数动物的感觉体验是多通道的，一种感觉通道的活动通常会导致 另一种形态的长期变化。这种跨模式的可塑性不仅导致补偿 感觉功能在感觉剥夺的情况下，也允许正常个体做出正确的反应 在他们独特的环境或情况下对感觉刺激的影响，并导致个体在 对多感官线索的感知。尽管跨模式可塑性很重要，但潜在的电路和 分子机制还不是很清楚。在拟议的研究中，一种新的形式的跨模式 在果蝇中发现了可塑性，并发展成为一种研究潜在的 在行为、回路、突触和分子水平上的机制。该系统允许比较 同一感觉系统中的跨通道和特定通道的可塑性。一项基因筛查发现 新的跨模式可塑性调节器。拟议研究的目标是确定 果蝇躯体感觉系统发育过程中跨模式可塑性的机制 并为指导其他物种未来的研究提供了电路和分子模型。中环 假设在发育过程中温和的机械感觉输入加强了5-羟色胺能抑制 从伤害性感受器到多感觉二级神经元的突触传递，即 是通过MSON中的特定基因实现的。这一假设将通过识别电路(AIM)进行验证 1)和分子(目标2)跨模式可塑性的机制。拟议的研究是 创新是因为它提出了不同机制的新概念，这些机制是跨模式和 并将使用一种新的系统，该系统可以使用遗传筛查来 研究跨模式可塑性。这项研究具有重要意义，因为它有望：1)阐明杂交是如何 情态和情态特有的可塑性在发育中的感觉系统中共存，并展示了 神经调制中间神经元在发育过程中建立跨模式可塑性；2)识别一种新的 跨模式可塑性的基础的分子机制，尤其是区别于 同一神经回路中特定形态的可塑性；3)产生多学科的、最先进的 识别支配经验依赖的神经组装的原理的实验系统 用于多感官整合的电路。此外，因为许多神经发育的共同问题 障碍是失调的多感官整合，拟议的研究将提供对 这些疾病的发病机制。

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.