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布线，其精度是通过出生后的经验依赖性细化来实现的。经验依赖性神经发育的经典模型系统是视觉系统中的眼优势可塑性，其中在生命早期的关键时期的单眼视觉剥夺改变了皮质反应。研究者最近发现，关键期的正常双眼视觉在视觉皮层中驱动双眼之间的定向偏好匹配，从而揭示了正常发育中关键期可塑性的生理目的。本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、在体全细胞记录和计算分析，以确定视皮层细胞在关键期之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，以揭示个体皮质细胞如何改变其单眼取向调谐以匹配双眼。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， 减少抑制的后果，并通过研究抑制性中间神经元亚型的双眼反应特性。总之，这些实验将提供重要的数据需要一个完整的理解双目匹配。由于眼优势可塑性及其关键期是人类弱视和斜视的模型系统，因此充分了解发育过程中通常发生的皮质变化将对理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.