DEVELOPING VISUAL CORTEX--AFFERENT TARGET RELATIONSHIPS

发育中的视皮层可塑性是指大脑在出生后发育过程中被环境变化所改变的敏感性，被认为是许多维持生命的神经功能的代表，如学习、记忆、感觉可塑性和衰老。此外，这一过程是形成正常神经连接的基础，而正常神经连接受到阻止正常感觉刺激的条件的攻击，包括斜视和儿童白内障。提出了一种研究发育可塑性的超微结构基础的研究计划，将示踪、免疫细胞化学和电子显微镜技术相结合，进行定性和定量的超微结构分析。这项研究的长期目标是了解谷氨酸和胆碱能受体在活性依赖性突触修饰中的作用，这些突触修饰是视觉可塑性的关键时期。一项新开发的技术将用于双重识别发育中的丘脑皮质(TC)轴突和化学指定的靶点，以确定丘脑终末和神经递质受体之间的传入-靶向关系。具体地说，1)丘脑皮质轴突接触部位的形态特征和靶标的GABA含量，2)TC轴突与NMDA、代谢型和AMPA型谷氨酸受体的连接模式，3)TC轴突与M受体之间的关系，将在视觉可塑性关键期之前、期间和之后在视皮层IV层和亚板中进行研究。这项拟议研究的具体目标是识别导致丘脑轴突细化和分离成眼优势柱的瞬时细胞机制，并通过突触巩固终止早期皮质可塑性。关于神经回路如何在结构上利用与可塑性有关的神经蛋白的知识，可能会为理解正常大脑功能的机制以及感觉剥夺造成的情况提供见解。

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.