Reduction of long-term potentiation in the dentate gyrus of the rat following selective depletion of monoamines.

1. Brief, high-frequency stimulation of the perforant path results in a long-term potentiation (l.t.p.) of the field response evoked in the dentate gyrus by single shocks to the perforant path. We have compared the magnitude and duration of l.t.p. in normal, anaesthetized rats with animals depleted of noradrenaline (NA), 5-hydroxytryptamine (5-HT), or both. 2. All animals were exposed to an identical sequence of eight high-frequency trains of increasing intensity given over a period of 140 min to the perforant path of one hemisphere. The potential evoked by test shocks to the perforant path was monitored in both hemispheres throughout this period and for a further 96 min after the last train. 3. Plots of the mean potentiation of the population e.p.s.p. as a function of time were computed for all animals in each group. L.t.p. in the NA-depleted group was about 50% of that in the non-depleted control group throughout the course of the experiment. L.t.p. in the 5-HT-depleted group was more severely affected; mean potentiation did not exceed 30% of that in the control group at any time. 4. The duration of l.t.p. was unaffected by NA depletion and reduced by 5-HT depletion. 5. The threshold for the intensity of high-frequency current pulses necessary to elicit l.t.p. was unaffected by NA depletion and raised by 5-HT depletion. 6. Short-term potentiation of the population e.p.s.p. was unaffected by either NA depletion or 5-HT depletion. 7. The effect of monoamine depletion on granule cell excitability was investigated. 5-HT depletion, but not NA depletion, induced an increase in the excitability of the granule cell population, in the sense that a population e.p.s.p. of a given size was associated with a larger population spike. 8. Long-term potentiation of granule cell excitability was not affected by NA depletion, but was reduced by 5-HT depletion. 9. These results show that monoamines can modulate long-term changes in synaptic function in the dentate gyrus, and suggest that 5-HT is more potent in this respect than NA.