期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：48
页码：17483-17488
DOI：10.1073/pnas.0503624102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Nitric oxide ([IMG]f1.gif" BORDER="0">) production in response to stimulation of the NMDA glutamate receptor is implicated not only in the synaptic plasticity in hippocampus but may also participate in excitotoxic cell death. Using [IMG]f1.gif" BORDER="0">-selective microssensors inserted into the diffusional field of [IMG]f1.gif" BORDER="0"> in acute hippocampal slices, we describe the [IMG]f1.gif" BORDER="0"> concentration dynamics evoked by NMDA receptor activation and report profound differences along the trisynaptic loop of the hippocampus. We measured the oxygen gradient across the slice thickness and conclude that [IMG]f1.gif" BORDER="0"> measurements were performed at cell layers experiencing physiological oxygen tensions. Recordings performed at increasing distances from the point of NMDA receptor stimulation resulted in a progressive decrease of [IMG]f1.gif" BORDER="0"> signals, reaching undetectable levels for distances >400 {micro}m, supporting the notion of a wide diffusional spread of endogenously generated [IMG]f1.gif" BORDER="0"> in the hippocampus. Neither a picoinjection nor a continuous perfusion of NMDA resulted in high steady-state [IMG]f1.gif" BORDER="0"> levels; rather all signals were transient, suggesting that cells are able to efficiently respond to high [IMG]f1.gif" BORDER="0"> concentrations (typically 200-400 nM) bringing it to very low nM levels; the claimed high micromolar [IMG]f1.gif" BORDER="0"> range achieved by excessive stimulation of NMDA receptor may have to be reevaluated. The distinct responses to NMDA receptor stimulation along the trysynaptic loop suggest a differential [IMG]f1.gif" BORDER="0"> activity and/or regulation among the hippocampal subregions. These findings may be relevant for the understanding of the role of [IMG]f1.gif" BORDER="0"> in physiologic mechanisms in the hippocampus and the differential sensitivity of the hippocampal subregions to NMDA receptor-dependent neurodegeneration.
关键词：carbon fiber microelectrode ; NO diffusional spread ; hippocampus
