Parker David, Bevan Sarah
Department of Physiology, Development, and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
J Neurophysiol. 2007 Jan;97(1):44-56. doi: 10.1152/jn.00717.2006. Epub 2006 Oct 4.
Variability is increasingly recognized as a characteristic feature of cellular, synaptic, and network properties. While studies have traditionally focused on mean values, significant effects can result from changes in variance. This study has examined cellular and synaptic variability in the lamprey spinal cord and its modulation by the neuropeptide substance P. Cellular and synaptic variability differed in different types of cell and synapse. Substance P reduced the variability of subthreshold locomotor-related depolarizations and spiking in motor neurons during network activity. These effects were associated with a reduction in the variability of spiking in glutamatergic excitatory network interneurons and with a reduction in the variance of excitatory interneuron-evoked excitatory postsynaptic potentials (EPSPs). Substance P also reduced the variance of postsynpatic potentials (PSPs) from crossing inhibitory and excitatory interneurons, but it increased the variance of inhibitory postsynpatic potentials (IPSPs) from ipsilateral inhibitory interneurons. The effects on the variance of different PSPs could occur with or without changes in the PSP amplitude. The reduction in the variance of excitatory interneuron-evoked EPSPs was protein kinase A, calcium, and N-methyl-d-aspartate (NMDA) dependent. The NMDA dependence suggested that substance P was acting postsynaptically. This was supported by the reduced variability of postsynaptic responses to glutamate by substance P. However, ultrastructural analyses suggested that there may also be a presynaptic component to the modulation, because substance P reduced the variability of synaptic vesicle diameters in putative glutamatergic terminals. These results suggest that cellular and synaptic variability can be targeted for modulation, making it an additional source of spinal cord plasticity.
变异性越来越被认为是细胞、突触和网络特性的一个特征。虽然传统研究主要关注平均值，但方差的变化可能会产生显著影响。本研究考察了七鳃鳗脊髓中的细胞和突触变异性及其受神经肽P物质的调节。不同类型的细胞和突触中，细胞和突触变异性存在差异。在网络活动期间，P物质降低了运动神经元阈下运动相关去极化和放电的变异性。这些效应与谷氨酸能兴奋性网络中间神经元放电变异性的降低以及兴奋性中间神经元诱发的兴奋性突触后电位（EPSP）方差的降低有关。P物质还降低了来自交叉抑制性和兴奋性中间神经元的突触后电位（PSP）的方差，但增加了来自同侧抑制性中间神经元的抑制性突触后电位（IPSP）的方差。对不同PSP方差的影响可能在PSP幅度改变或未改变的情况下发生。兴奋性中间神经元诱发的EPSP方差的降低依赖于蛋白激酶A、钙和N-甲基-D-天冬氨酸（NMDA）。对NMDA的依赖性表明P物质在突触后起作用。P物质降低了对谷氨酸的突触后反应的变异性，这支持了这一点。然而，超微结构分析表明，调节可能也存在突触前成分，因为P物质降低了假定的谷氨酸能终末中突触小泡直径的变异性。这些结果表明，细胞和突触变异性可以作为调节靶点，使其成为脊髓可塑性的另一个来源。
