Gally J A, Montague P R, Reeke G N, Edelman G M
Neurosciences Institute Neurosciences Research Program, New York, NY 10021.
Proc Natl Acad Sci U S A. 1990 May;87(9):3547-51. doi: 10.1073/pnas.87.9.3547.
Several observations suggest that the Ca2(+)-dependent postsynaptic release of nitric oxide (NO) may be important in the formation and function of the vertebrate nervous system. We explore here the hypothesis that the release of NO and its subsequent diffusion may be critically related to three aspects of nervous system function: (i) synaptic plasticity and long-term potentiation in certain regions of the adult nervous system, (ii) the control of cerebral blood flow in such regions, and (iii) the establishment and activity-dependent refinement of axonal projections during the later stages of development. In this paper, we detail and analyze the basic assumptions underlying this NO hypothesis and describe a computer simulation of a minimal version of the hypothesis. In the simulation, a 3-dimensional volume of neuropil is presented with patterned afferent input; NO is produced, diffuses, and is destroyed; and synaptic strengths are determined by a set of synaptic rules based on the correlation of synaptic depolarization and NO levels. According to the hypothesis, voltage-dependent postsynaptic release of this rapidly diffusing substance links the activities of neurons in a local volume of tissue, regardless of whether the neurons are directly connected by synapses. This property is demonstrated in the simulation, and it is this property that is exploited in the hypothesis to account for certain aspects of long-term potentiation and activity-dependent sharpening of axonal arbors.
多项观察结果表明，一氧化氮（NO）的Ca2+依赖性突触后释放可能在脊椎动物神经系统的形成和功能中发挥重要作用。在此，我们探讨这样一种假说，即NO的释放及其随后的扩散可能与神经系统功能的三个方面密切相关：（i）成年神经系统某些区域的突触可塑性和长时程增强；（ii）这些区域的脑血流量控制；以及（iii）发育后期轴突投射的建立和活动依赖性精细化。在本文中，我们详细阐述并分析了这一NO假说背后的基本假设，并描述了该假说最简版本的计算机模拟。在模拟中，向三维神经毡体积呈现模式化传入输入；NO产生、扩散并被破坏；突触强度由一组基于突触去极化与NO水平相关性的突触规则确定。根据该假说，这种快速扩散物质的电压依赖性突触后释放将局部组织体积内神经元的活动联系起来，无论这些神经元是否通过突触直接相连。这一特性在模拟中得到了证明，正是利用这一特性，该假说解释了长时程增强和轴突分支活动依赖性锐化的某些方面。
