Nitric oxide-induced potentiation of CA1 hippocampal synaptic transmission during baseline stimulation is strictly frequency-dependent.
Nitric oxide (NO) has been hypothesised to serve a signalling role in certain types of synaptic plasticity. If so, exogenously applied NO should be able to elicit those same plastic changes under appropriate conditions. In the case of hippocampal long-term potentiation (LTP), however, existing evidence is discrepant. Field recordings of synaptic transmission in the CA1 area of rat hippocampal slices were used to re-examine this issue. Under 0.2 Hz afferent fibre stimulation, NO (delivered using two different NONOates) produced, concentration-dependently, a depression of synaptic transmission. On washout of NO, the depression gave way to a persistent potentiation, the amplitude of which was also graded with NONOate concentration. Tetanus-induced LTP, induced an hour after washout, was occluded in proportion to the degree of prior NO-induced potentiation. At a lower stimulation frequency of 0.033 Hz, the depression was unaltered but no rebound potentiation took place and subsequent tetanus-induced LTP was normal. Tests indicated that there is a clear time-window during which 0.2 Hz stimulation needs to be applied relative to the delivery of NO to produce a potentiation. The findings explain previous divergent results and indicate that exogenous NO-triggered potentiation depends critically on the frequency of synaptic transmission.
The Wolfson Institute for Biomedical Research, University College London, The Cruciform Building, Gower Street, London WC1E 6BT, UK.
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Garthwaite
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D006834:Hydrazines / Q000494:pharmacology; D019811:Hydroxylamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009589:Nitrogen Oxides; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
D006834:Hydrazines; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D009599:Nitroprusside; D019811:Hydroxylamine; D009569:Nitric Oxide; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine