Critical period in visual cortex: inhibitory circuits

描述（由申请人提供）：神经科学的一个核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，在关键时期，皮层内抑制回路的成熟是启动和驱动眼优势可塑性的必要条件。然而，所涉及的特定类型的抑制回路的成熟和调节尚不清楚。尽管细胞机制尚不清楚，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能神经元的一个特定亚型，小白蛋白（Pv）篮中间神经元的功能成熟是关键时期可塑性抑制机制的一个组成部分，也是经验剥夺和BDNF调节的细胞靶点。以表达GFP的细菌人工染色体转基因（BAC）小鼠pv -中间神经元为研究对象，利用双光子激光扫描显微镜和脑电生理切片对pv -中间神经元的形态和生理发育进行了研究。然后，我们将研究暗育对pv -中间神经元成熟的影响。最后，我们将利用BAC转基因小鼠在pv - interneurn中特异性表达trkB受体的显性阴性形式，通过阻断trkB信号传导，来测试BDNF在pv - interneurn经验依赖性成熟中的作用。这些结果将揭示经验塑造已识别的抑制网络功能的机制，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编码。所获得的知识将有助于设计疾病状态（如癫痫和精神分裂症）的药物治疗。

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.