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Title: Concentration dynamics of nitric oxide in rat hippocampal subregions evoked by stimulation of the NMDA glutamate receptor
Authors: Ledo, Ana 
Barbosa, Rui M. 
Gerhardt, Greg A. 
Cadenas, Enrique 
Laranjinha, João 
Keywords: Carbon fiber microelectrode; NO diffusional spread; hippocampus
Issue Date: 29-Nov-2005
Publisher: National Academy of Sciences
Citation: PNAS. 102:48 (2006) 17483-17488
Abstract: Nitric oxide (*NO) 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 *NO-selective microssensors inserted into the diffusional field of *NO in acute hippocampal slices, we describe the *NO 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 *NO 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 *NO signals, reaching undetectable levels for distances >400 microm, supporting the notion of a wide diffusional spread of endogenously generated *NO in the hippocampus. Neither a picoinjection nor a continuous perfusion of NMDA resulted in high steady-state *NO levels; rather all signals were transient, suggesting that cells are able to efficiently respond to high *NO concentrations (typically 200-400 nM) bringing it to very low nM levels; the claimed high micromolar *NO 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 *NO activity and/or regulation among the hippocampal subregions. These findings may be relevant for the understanding of the role of *NO in physiologic mechanisms in the hippocampus and the differential sensitivity of the hippocampal subregions to NMDA receptor-dependent neurodegeneration
ISSN: 0027-8424
DOI: 10.1073/pnas.0503624102
Rights: openAccess
Appears in Collections:FFUC- Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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