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38. Concentration dynamics of nitric oxide in rat hippocampal subregions evoked by stimulation of the NMDA glutamate receptor

Author

Ledo, Ana, Barbosa, Rui M., Gerhardt, Greg A., Cadenas, Enrique, and Laranjinha, Joao

Subjects
Rats -- Research, Rattus -- Research, Hippocampus (Brain) -- Research, Nitric oxide -- Research, Science and technology
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 [micro]m, 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. carbon fiber microelectrode | NO diffusional spread | hippocampus

Published
2005

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