Critical Period Plasticity and Binocular Matching in the Visual Cortex

描述(申请人提供)：神经系统的最佳功能需要选择性地连接神经回路，其精确度是通过出生后依赖经验的改进而实现的。经验依赖型神经发育的经典模型系统是视觉系统中的眼优势可塑性，在早期生命的关键时期，单眼视觉剥夺会改变皮质反应。研究人员最近发现，关键期的正常双眼视觉驱动双眼在视皮层中的方位偏好匹配，从而揭示了正常发育关键期可塑性的生理目的。这些实验旨在研究新发现的双眼匹配过程的突触和回路机制。首先，将进行单单位细胞外记录、体内全细胞记录和计算分析，以确定在临界期之前视觉皮层细胞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方向调节，以匹配双眼之间。最后，研究人员将通过研究来研究抑制在双眼匹配过程中的作用 减少抑制的结果，并通过研究抑制性中间神经元亚型的双眼反应特性。总之，这些实验将提供完全理解双目匹配所需的重要数据。由于眼优势可塑性及其关键期是人类弱视和斜视的一个模型系统，充分了解发育过程中正常发生的皮质变化对于了解和治疗这些疾病具有重要意义。

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.