Critical period in visual cortex: inhibitory circuits

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。最近的研究表明，视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。关键期可塑性也受到视觉剥夺和BDNF过度表达的调节，尽管其细胞机制尚不清楚。在这里，我们假设一个特定的GABA能神经元亚型，小白蛋白（PV）篮中间神经元的功能成熟，是关键期可塑性的抑制机制的一个组成部分，和经验剥夺和BDNF调节的细胞靶点。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，我们将测试BDNF在PV-中间神经元的经验依赖性成熟中的作用，通过使用在PV-中间神经元中特异性表达显性阴性形式的trkB受体的BAC转基因小鼠阻断trkB信号传导。这些结果将揭示一种机制，通过这种机制，经验的形状功能的一个确定的抑制网络，并提供强有力的证据，成熟的PV-interneuron电路促进编码的视觉信息，必要的驱动眼优势可塑性。所获得的知识将有助于设计药物治疗疾病状态，如癫痫和精神分裂症。

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.