DEVELOPING VISUAL CORTEX--AFFERENT TARGET RELATIONSHIPS

发育性视觉皮层可塑性是指大脑在出生后发育过程中对环境变化的易感性，被认为是学习、记忆、感觉可塑性和衰老等许多维持生命的神经功能的代表。此外，这一过程是正常神经连接形成的基础，而正常的神经连接会受到包括斜视和儿童白内障在内的阻止正常感觉刺激的疾病的攻击。拟结合细胞示踪、免疫细胞化学和电镜等技术，对发育可塑性的超微结构基础进行定性和定量研究。本研究的长期目标是了解谷氨酸和胆碱能受体在活动依赖性突触修饰中的作用，这些突触修饰是视觉可塑性关键时期的基础。一项新开发的技术将用于双重识别发展中的丘脑皮质（TC）轴突和化学指定的靶点，以确定丘脑终端和神经递质受体之间的传入-靶点关系。具体而言，在视觉可塑性关键期之前、期间和之后，我们将在视觉皮层第四层和亚板中研究1)丘脑皮层轴突接触部位的形态学特征和目标GABA含量，2)TC轴突与NMDA、代谢和AMPA型谷氨酸受体的连接模式，以及3)TC轴突与毒毒碱受体的关系。该研究的具体目标是确定导致丘脑轴突细化和分离为眼优势柱的短暂细胞机制，以及通过突触巩固终止早期皮层可塑性。了解与可塑性有关的神经蛋白如何在结构上被神经回路利用，可以为理解正常大脑功能的机制以及感觉剥夺所导致的条件提供见解。

Developmental visual cortex plasticity, the susceptibility of the brain to be modified by the environmental changes during postnatal development, is deemed representative of many life-sustaining neural functions such as learning, memory, sensory plasticity and aging. Furthermore, this process underlies the formation of normal neural connections, which is assailed by conditions that prevent normal sensory stimulation, including strabismus and childhood cataract. A research plan is proposed to study the ultastructural basis of developmental plasticity, combining tract-tracing, immunocytochemistry and electron microscopy techniques for qualitative and quantitative ultrastructural analysis. The long term objective of this research is to understand the roles of the glutamate and the cholinergic receptors in activity dependent synaptic modifications that underlie the critical period of visual plasticity. A newly developed technique will be used to dually identify developing thalamocortical(TC) axons and the chemically specified target sites to determine afferent-target relationships between thalamic terminals and the neurotransmitter receptors. Specifically, 1) the morphological properties of sites contacted by thalamocortical axons, and the GABA content of the targets, 2) the connection pattern of TC axons on NMDA, metabotropic and AMPA type glutamate receptors, and 3) the relationships between TC axons and the muscarinic receptors, will be examined in visual cortex layer IV and the subplate, before, during and after the critical period of visual plasticity. The specific goals of the proposed research address the identification of transient cellular mechanisms that lead to refinement and segregation of thalamic axons into ocular dominance columns, and to termination of early cortical plasticity by synaptic consolidation. The knowledge on how the neural proteins that are implicated in plasticity are structurally utilized by neural circuitry may provide insights in understanding the mechanisms of normal brain function as well as the conditions result from the sensory deprivation.