Mechanisms for self-organization of cerebral cortical circuitry

基因和学习机制之间的相互作用是如何构建(自组织)皮质回路的？这一直是发育神经生物学的核心问题之一。这项研究揭示了视觉皮质(VC)中指定特定层神经元连接到什么靶点的层状结构的发展，完全依赖于基因机制。用大鼠外侧膝状核块和幼年大鼠的Vc切片共同培养，可复制正常Vc的所有板层结构。本研究的另一个发现是在大鼠Vc内发现了两种类型的长时程增强(LTP)，即1)慢时程且仅在幼年大鼠中诱导的慢时程增强(SLTP)和2)快时程时程的快时程(Fltp)，在幼年和成年大鼠中均诱导。SLTP的诱导依赖于电压门控钙通道的钙内流、基因转录和蛋白质合成，表达于膝状体-皮质突触；而Fltp的诱导依赖于钙离子通过NMDA通道的内流，表达于皮质传出神经的轴突侧支突触。这些观察表明，sLTP是婴幼儿Vc柱状结构形成的发育可塑性基础，而Fltp是成人Vc可塑性的基础。

How is the cortical circuitry constructed (self-organized) by interaction between gene and learning mechanisms? This has been one of the central problems in the developmental neurobiology. This study revealed that the development of the laminar structures in the visual cortex (VC) specifying what targets neurons in a particular layr are connected to, totally depend on the gene mechanisms. All laminar structures in the normal VC are reproduced in the coculture preparations where a block of the lateral geniculate nucleus and a VC slice of infant rats were cultured together.Another finding of the present study is demonstration of two types of long term potentiation (LTP) in rat VC,i. e., 1) slow LTP (sLTP) which had a slow time course and was only induced in infant rats, and 2) fast LTP (fLTP) which had a fast time course and was induced both in infant and adult rats. Induction of sLTP depended on Ca entry through voltage gated Ca channels, gene transcription as well as protein synthesis and was expressed in the geniculo-cortical synapses, while that of fLTP depended on Ca entry through NMDA channels and was expressed in the axon collateral synapses of the cortical efferents. These observations indicate that sLTP underlies the developmental plasticity for formation of the columnar structures in infant VC,while fLTP is the basis for the plasticity in adult VC.