Critical Period Plasticity and Binocular Matching in the Visual Cortex

项目总结/摘要 神经系统的最佳功能需要神经回路的选择性布线， 这是通过出生后的经验依赖的改进来实现的。一个经典的经验模型系统- 依赖性神经发育是视觉系统中的眼优势可塑性，其中单眼视觉 在生命早期的关键时期，剥夺会改变大脑皮层的反应。调查人员最近发现 关键期正常的双眼视觉驱动着两者之间的方位偏好匹配 眼睛在视觉皮层，从而揭示了生理目的的关键期可塑性，在正常 发展拟议的实验旨在研究大脑皮层和丘脑的机制， 双目匹配过程在第一个目标中，双光子钙成像将长期进行，以揭示如何 单个皮层细胞改变它们的单眼定向调谐以在两只眼睛之间匹配。此外，本发明还提供了一种方法， 双光子成像和电生理记录将用于表征双眼反应 在关键期之前、期间和之后，抑制性神经元亚型的特性。在目标二， 将进行电生理记录，以确定是否有更多的双眼神经元， 背外侧膝状体核（dLGN）的年轻小鼠比成年小鼠，以及是否这些双眼dLGN 神经元在V1之前显示出显著的方向偏好匹配。其他实验将 执行以确定dLGN中的早期匹配是否是经验依赖性的， 老鼠从出生起就在完全黑暗的环境中长大。最后，通过结合皮质沉默和体内全细胞， 记录，研究人员将检查dLGN输入的双眼反应是否决定双眼 单个V1神经元的调谐。总之，这些实验将揭示一个新的联系之间的发展 可塑性的两个连续阶段的视觉处理，并确定视觉丘脑的作用，指导 V1期双眼发育。由于眼优势可塑性及其关键期是弱视的模型 和斜视，充分了解皮质和皮质下的变化，通常发生在 发展将对理解和治疗这些疾病产生深远影响。

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.