Critical period in visual cortex: inhibitory circuits

视觉皮层的关键期：抑制回路

• 批准号: 6605702
• 负责人: SANDRA J KUHLMAN
• 金额: $ 4.73万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-28 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6605702
• 关键词: Critical; period; visual; cortex; inhibitory

DESCRIPTION (provided by applicant): A central issue in neuroscience is to understand how experience shapes brain function. Recent studies in visual cortex suggest that the maturation of intracortical inhibitory circuits is necessary to initiate and drive ocular dominance plasticity during the critical period. However, the maturation and regulation of the specific type of inhibitory circuit involved is not understood. Critical period plasticity is also modulated by visual deprivation and BDNF over-expression, although the cellular mechanisms remain unknown. Here we hypothesize that the functional maturation of a specific subtype of GABAergic neurons, parvalbumin (Pv) basket interneurons, are a component of the inhibitory mechanism underlying critical period plasticity, and a cellular target of experience deprivation and BDNF regulation. Using bacterial artificial chromosome transgenic (BAC) mice expressing GFP in Pv-interneurons, we will characterize the morphological and physiological development of Pv-interneurons using two photon laser scanning microscopy and electrophysiology in brain slices. We will then examine the effects of dark rearing on the maturation of Pv-interneurons. Finally, we will test the role of BDNF in experience-dependent maturation of Pv-interneurons by blocking trkB signaling using BAC transgenic mice expressing a dominant negative form of trkB receptor specifically in Pv-intemeurons. These results will reveal a mechanism by which experience shapes function of an identified inhibitory network and provide strong evidence that maturation of the Pv-interneuron circuit facilitates the coding of visual information necessary to drive ocular dominance plasticity. The knowledge gained will aid in the design of drug treatments in diseased states such as epilepsy and schizophrenia.

描述（由申请人提供）：神经科学的一个中心问题是了解经验如何塑造大脑功能。最近对视觉皮层的研究表明，皮质内抑制回路的成熟对于在关键时期启动和驱动眼部优势可塑性是必要的。然而，所涉及的特定类型抑制回路的成熟和调节尚不清楚。尽管细胞机制仍不清楚，但关键期可塑性也受到视觉剥夺和 BDNF 过度表达的调节。在这里，我们假设 GABA 能神经元的特定亚型（小白蛋白（Pv）篮子中间神经元）的功能成熟是关键期可塑性抑制机制的组成部分，也是经验剥夺和 BDNF 调节的细胞目标。使用在 Pv 中间神经元中表达 GFP 的细菌人工染色体转基因 (BAC) 小鼠，我们将使用双光子激光扫描显微镜和脑切片中的电生理学来表征 Pv 中间神经元的形态和生理发育。然后我们将研究黑暗饲养对 Pv 中间神经元成熟的影响。最后，我们将通过使用 BAC 转基因小鼠阻断 trkB 信号传导来测试 BDNF 在 Pv 中间神经元的经验依赖性成熟中的作用，该小鼠特异地在 Pv 中间神经元中表达 trkB 受体的显性失活形式。这些结果将揭示一种机制，通过该机制，经验塑造已识别的抑制网络的功能，并提供强有力的证据，证明 Pv 中间神经元回路的成熟促进了驱动眼优势可塑性所需的视觉信息的编码。获得的知识将有助于设计针对癫痫和精神分裂症等疾病的药物治疗。