Critical Period Plasticity and Binocular Matching in the Visual Cortex

描述（由申请人提供）：神经系统的最佳功能需要神经回路的选择性连接，其精度是通过出生后的经验依赖的改进来实现的。经验依赖神经发育的一个经典模型系统是视觉系统中的眼优势可塑性，其中早期生命关键时期的单眼视觉剥夺会改变皮层反应。研究者最近发现，正常的双眼视觉在关键期驱动视觉皮层中两眼之间的定向偏好匹配，从而揭示了正常发育关键期可塑性的生理目的。本实验旨在研究新发现的双目匹配过程的突触和电路机制。首先，通过单细胞外记录、体内全细胞记录和计算分析来确定视觉皮层细胞在关键期前对双眼刺激的反应以及突触抑制在这一双眼整合过程中的作用。其次，将进行慢性双光子钙成像，以揭示单个皮质细胞如何改变其单眼定向调谐以匹配两只眼睛。最后，研究者将通过研究来探讨抑制在双眼匹配过程中的作用

DESCRIPTION (provided by applicant): 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 shifts 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 the synaptic and circuit mechanisms of the newly- discovered binocular matching process. First, single unit extracellular recording, in vivo whole cell recording, and computational analysi will be carried out to determine how visual cortical cells respond to binocular stimulation before the critical period and the role of synaptic inhibition in this binocular integration process. Second, chronic 2-photon calcium imaging will be performed to reveal how individual cortical cells change their monocular orientation tunings to match between the two eyes. Finally, the investigators will investigate the role of inhibition in the binocular matching process by studying the consequence of reducing inhibition, and by studying binocular response properties of subtypes of inhibitory interneurons. Together, these experiments will provide important data needed for a complete understanding of binocular matching. Because ocular dominance plasticity and its critical period is a model system for human amblyopia and strabismus, a full understanding of cortical changes that normally take place during development will have important implications for the understanding and treatment of these diseases.