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 (MRF) may modulate long-term potentiation (LTP) 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 (10 trains of 8 pulses at 400 Hz, delivered at 5 min intervals). The magnitude and duration of LTP of the population spike in this control condition were compared with that observed when a low-intensity MRF stimulation was delivered 10 s after each train to the perforant path. Post-event MRR stimulation enhanced the amount of LTP 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 MRF stimulation in the absence of perforant path high-frequency stimulation or when this failed to induce significant LTP. The temporal gradient of efficacy of MRF stimulation was investigated. MRF stimulation delivered 10 s after a single high-frequency stimulation of perforant path fibers resulted in an enhanced LTP of both the population excitatory post-synaptic potential (EPSP) and population spike. LTP was unaffected by MRF stimulation given either before, or 120 s after perforant path high-frequency stimulation. Low-intensity MRF stimulation enhances lasting changes in synaptic function in the dentate gyrus when delivered during a critical period following high-frequency activation of perforant path fibers. The results are discussed in the light of the effects of post-event MRF stimulation on memory and on the development of associative changes in hippocampal multiunit activity during conditioning. LTP-like mechanisms may be involved in the stabilization of neural networks by experience and this process might be reinforced by diffuse MRF activation.