Inhibitory mechanisms for sensory map plasticity in cerebral cortex.

描述（由申请人提供）：感觉经验有力地调节出生后晚期发育和大脑回路的成人功能，特别是在大脑皮层中。介导这一过程的细胞机制尚不清楚，但对理解皮质神经发育障碍，包括自闭症，青少年癫痫和精神发育迟滞具有重要意义。这个项目的重点是经验控制大脑皮层兴奋和抑制平衡的新机制。这是在啮齿动物的躯体感觉皮层中研究的，这是皮层功能的典型模型系统。 经验依赖性发展和修改（可塑性）的标准模型关注兴奋性皮层回路。然而，最近的研究结果表明，抑制回路也表现出强大的可塑性的感觉经验。抑制性可塑性的普遍性、细胞机制和机制作用在很大程度上是未知的。使用细胞和系统水平的神经生理学技术，我们将确定特定的抑制性神经元和电路，由感觉经验，表征这种可塑性的细胞机制，并确定其在皮质功能中的作用。我们专门测试的假设，抑制可塑性具有双重作用：保持兴奋-抑制平衡，并在不断变化的感觉使用过程中介导快速稳态的感觉反应。大量的初步数据支持这一提议。总的来说，这项工作将扩大我们的理解皮层发展超出基本的可塑性兴奋电路，包括快速，强大的可塑性抑制。结果可能表明，神经发育障碍，包括青少年癫痫和自闭症，这可能是由于兴奋-抑制平衡的发展不当的一个新的基础。这项工作可能会导致这些疾病的改善动物模型和新的治疗策略。

DESCRIPTION (provided by applicant): Sensory experience powerfully regulates late postnatal development and adult function of brain circuits, particularly in the cerebral cortex. The cellular mechanisms that mediate this process are not yet understood, but have major implications for understanding cortical neurodevelopmental disorders, including autism, juvenile epilepsy, and mental retardation. This project focuses on novel mechanisms by which experience controls the balance of excitation and inhibition in cerebral cortex. This is studied in the somatosensory cortex of rodents, which is a canonical model system for cortical function. Standard models of experience-dependent development and modification (plasticity) focus on excitatory cortical circuits. However, recent findings indicate that inhibitory circuits also show robust plasticity by sensory experience. The prevalence, cellular mechanisms, and mechanistic role of inhibitory plasticity are largely unknown. Using cellular and systems-level neurophysiology techniques, we will identify specific inhibitory neurons and circuits that are regulated by sensory experience, characterize the cellular mechanisms for this plasticity, and determine its role in cortical function. We specifically test the hypothesis that inhibitory plasticity has a dual role: to maintain excitatory-inhibitory balance, and to mediate rapid homeostasis of sensory responses during changing sensory use. Substantial preliminary data support the proposal. Overall, this work will extend our understanding of cortical development beyond basic plasticity of excitatory circuits, to include rapid, robust plasticity of inhibition. Results may suggest a novel basis for neurodevelopmental disorders including juvenile epilepsy and autism, which may arise from improper development of excitatory-inhibitory balance. This work may lead to improved animal models and novel therapeutic strategies for these diseases.