Enhancement of long-term potentiation in the rat dentate gyrus by post-trial stimulation of the reticular formation

Abstract

The possibility that post-trial stimulation of the mesencephalic reticular formation (m.r.f.) may modulate long-term potentiation (l.t.p.) at the perforant path to dentate granule cell synapses was studied in freely moving rats. Extracellular potentials evoked in the dentate gyrus by test pulses to the perforant path were recorded before and at various delays after a series of high-frequency stimulus trains to the perforant path (ten trains of eight pulses at 400 Hz, delivered at 5 min intervals). We have compared the magnitude and duration of l.t.p. of the population spike in this control condition with that observed when a low-intensity m.r.f. stimulation was delivered 10 s after each train to the perforant path. Post-event m.r.f. stimulation enhanced the amount of l.t.p. induced by the series of high-frequency stimulus trains and prolonged its duration for several days. The size of the population spike was unaffected by repeated m.r.f. stimulation in the absence of perforant path high-frequency stimulation, or when this failed to induce significant l.t.p. The temporal gradient of efficacy of m.r.f. stimulation was investigated. M.r.f. stimulation delivered 10 s after a single high-frequency stimulation of perforant path fibres resulted in an enhanced l.t.p. of both the population excitatory post-synaptic potential (e.p.s.p.) and population spike. L.t.p. was unaffected by m.r.f. stimulation given either before, or 120 s after perforant path high-frequency stimulation. These results show that low-intensity m.r.f. stimulation enhances lasting changes in synaptic function in the dentate gyrus when delivered during a critical period following high-frequency activation of perforant path fibres. These results are discussed in the light of our previous findings on the effects of post-event m.r.f. stimulation on memory and on the development of associative changes in hippocampal multiunit activity during conditioning. It is hypothesized that l.t.p.-like mechanisms may be involved in the stabilization of neural networks by experience and that this process might be reinforced by diffuse m.r.f. activation.