Mechanisms for self-organization of cerebral cortical circuitry

在基因和学习机制的相互作用下，皮层回路是如何构建（自组织）的？这一直是发育神经生物学的核心问题之一。本研究揭示了视觉皮层（VC）层状结构的发育完全取决于基因机制，该结构决定了特定层中目标神经元的连接。将大鼠侧膝状核块与幼年大鼠侧膝状核片共培养，可复制正常VC的所有层状结构。本研究的另一个发现是在大鼠VC中存在两种类型的长时程增强（LTP）。即，1)慢速LTP (sLTP)，其病程较慢，仅在幼龄大鼠中诱导；2)快速LTP (fLTP)，其病程较快，在幼龄和成年大鼠中均可诱导。sLTP的诱导依赖于钙通过电压门控通道进入，基因转录和蛋白质合成，并在geniculo-cortical synapses中表达，而fLTP的诱导依赖于钙通过NMDA通道进入，并在皮层输出神经的轴突侧突突触中表达。这些观察结果表明，sLTP是婴儿VC柱状结构形成的发育可塑性的基础，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.