Nedivi E
Department of Brain and Cognitive Sciences, Center for Learning and Memory, Massachusetts Institute of Technology, 45 Carleton St., E25-435, Cambridge, Massachusetts 02139, USA.
J Neurobiol. 1999 Oct;41(1):135-47.
Gene expression studies indicate that during activity-dependent developmental plasticity, N-methyl-D-aspartate receptor activation causes a Ca(2+)-dependent increase in expression of transcription factors and their downstream targets. The products of these plasticity genes then operate collectively to bring about the structural and functional changes that underlie ocular dominance plasticity in visual cortex. Identifying and characterizing plasticity genes provides a tool for molecular dissection of the mechanisms involved. Members of second-messenger pathways identified in adult plasticity paradigms and elements of the transmission machinery are the first candidate plasticity genes tested for their role in activity-dependent developmental plasticity. Knockout mice with deletions of such genes have allowed analyzing their function in the context of different systems and in different paradigms. Studies of mutant mice reveal that activity-dependent plasticity is not necessarily a unified phenomenon. The relative importance of a gene can vary with the context of its expression during different forms of plasticity. Forward genetic screens provide additional new candidates for testing, some with well-defined cellular functions that provide insight into possible plasticity mechanisms.
基因表达研究表明，在依赖活动的发育可塑性过程中，N-甲基-D-天冬氨酸受体激活会导致转录因子及其下游靶点的表达出现钙依赖性增加。这些可塑性基因的产物随后共同作用，引发构成视觉皮层眼优势可塑性基础的结构和功能变化。识别和表征可塑性基因为剖析其中涉及的机制提供了一种分子工具。在成体可塑性范式中确定的第二信使途径成员以及传递机制的元件是首批被测试其在依赖活动的发育可塑性中作用的候选可塑性基因。缺失此类基因的基因敲除小鼠使得能够在不同系统和不同范式的背景下分析它们的功能。对突变小鼠的研究表明，依赖活动的可塑性不一定是一种统一的现象。一个基因的相对重要性可能会因其在不同形式可塑性过程中的表达背景而有所不同。正向遗传学筛选为测试提供了更多新的候选基因，其中一些具有明确的细胞功能，有助于深入了解可能的可塑性机制。
