Critical Period Plasticity and Binocular Matching in the Visual Cortex

项目摘要/摘要 神经系统的最佳功能需要选择性地连接神经电路，精确度 这是通过出生后依赖经验的精炼来实现的。一个经典的经验模型系统-- 依赖神经发育是视觉系统中的眼优势可塑性，其中单眼视觉 早期生命关键时期的剥夺会改变大脑皮层的反应。调查人员最近发现 关键时期的正常双眼视觉驱动着两者之间的定向偏好匹配 眼睛位于视皮层，从而揭示了正常情况下临界期可塑性的生理目的 发展。拟议的实验旨在研究大脑和丘脑的机制，这些机制是 双目匹配过程。在目标一中，将长期进行双光子钙成像，以揭示 单个皮质细胞改变它们的单眼方向调整，以匹配两只眼睛之间的位置。此外, 将使用双光子成像和电生理记录来表征双眼反应 临界期前、中、后抑制性神经元亚型的特性。在目标二中， 将进行电生理记录，以确定是否有更多的双眼神经元在 幼年小鼠的背外侧膝状体核(DLGN)比成年小鼠的背外侧膝状体核(DLGN)更强，而这些双眼dLGN 神经元在V1之前的定向偏好上表现出显著的匹配。其他实验将包括 执行以确定dLGN中的早期匹配是否依赖于经验 老鼠从出生起就在完全黑暗的环境中饲养。最后，通过结合皮质沉默和体内整个细胞 记录下来，研究人员将检查dLGN输入的双眼反应是否决定了双眼 单个V1神经元的调谐。综上所述，这些实验将揭示出一种新的联系，即 视觉加工的两个连续阶段的可塑性，并决定了视觉丘脑在引导中的作用 V1的双眼发育。因为眼优势可塑性及其临界期是弱视的一个模型 和斜视，充分了解皮质和皮质下的变化，通常发生在 发展将对这些疾病的理解和治疗产生深远的影响。

Project Summary/Abstract Optimal functioning of the nervous system requires selective wiring of neural circuits, the precision of which is achieved through experience-dependent refinement after birth. A classic model system of experience- dependent neural development is ocular dominance plasticity in the visual system, where monocular visual deprivation in a critical period of early life alters cortical responses. The investigators have recently discovered that normal binocular vision in the critical period drives the matching of orientation preference between the two eyes in the visual cortex, thus revealing a physiological purpose for critical period plasticity in normal development. The proposed experiments aim to study cortical and thalamic mechanisms that underlie the binocular matching process. In aim one, two-photon calcium imaging will be performed chronically to reveal how individual cortical cells change their monocular orientation tunings to match between the two eyes. In addition, two-photon imaging and electrophysiological recording will be used to characterize the binocular response properties of subtypes of inhibitory neurons before, during, and after the critical period. In aim two, electrophysiological recordings will be conducted to determine whether there are more binocular neurons in the dorsal lateral geniculate nucleus (dLGN) of young mice than in adults, and whether these binocular dLGN neurons show significant matching in their orientation preference before V1. Additional experiments will be performed to determine whether the early matching in the dLGN is experience-dependent by recording from mice reared in complete darkness from birth. Finally, by combining cortical silencing and in vivo whole cell recording, the investigators will examine whether the binocular responses of dLGN input determine the binocular tuning of individual V1 neurons. Together, these experiments will reveal a novel link between the developmental plasticity at two successive stages of visual processing, and determine the role of visual thalamus in guiding binocular development in V1. Because ocular dominance plasticity and its critical period is a model for amblyopia and strabismus, a full understanding of cortical and subcortical changes that normally take place during development will have profound implications for the understanding and treatment of these diseases.