Concentration dynamics of nitric oxide in rat hippocampal subregions evoked by stimulation of the NMDA glutamate receptor
Abstract
Nitric oxide ({\cdot}{N}{O}) 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 {\cdot}{N}{O}-selective microssensors inserted into the diffusional field of {\cdot}{N}{O} in acute hippocampal slices, we describe the {\cdot}{N}{O} 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 {\cdot}{N}{O} 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 {\cdot}{N}{O} signals, reaching undetectable levels for distances >400 μm, supporting the notion of a wide diffusional spread of endogenously generated {\cdot}{N}{O} in the hippocampus. Neither a picoinjection nor a continuous perfusion of NMDA resulted in high steady-state {\cdot}{N}{O} levels; rather all signals were transient, suggesting that cells are able to efficiently respond to high {\cdot}{N}{O} concentrations (typically 200-400 nM) bringing it to very low nM levels; the claimed high micromolar {\cdot}{N}{O} 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 {\cdot}{N}{O} activity and/or regulation among the hippocampal subregions. These findings may be relevant for the understanding of the role of {\cdot}{N}{O} in physiologic mechanisms in the hippocampus and the differential sensitivity of the hippocampal subregions to NMDA receptor-dependent neurodegeneration.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- November 2005
- DOI:
- 10.1073/pnas.0503624102
- Bibcode:
- 2005PNAS..10217483L
- Keywords:
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- NEUROSCIENCE