RESTORATION OF DECAYING LONG-TERM POTENTIATION IN THE HIPPOCAMPAL-FORMATION BY STIMULATION OF NEUROMODULATORY NUCLEI IN FREELY MOVING RATS

Induction of long-term potentiation within the hippocampal formation c an be modulated by afferent influences from a number of subcortical st ructures known to be involved in hippocampal-dependent learning and me mory. This study performed on freely moving rats investigated the effe cts of stimulation of the noradrenergic locus coeruleus nucleus and th e serotonergic dorsal raphe nucleus on spontaneously decaying postteta nic long-term potentiation in the dentate gyrus and the hippocampal CA 1 area, respectively. High-frequency electrical stimulation of the loc us coeruleus or the dorsal raphe elicited a well-expressed behavioural reaction of exploratory or defensive type. respectively, but did not significantly alter transmission at perforant path-dentate gyrus or Sc haffer collateral-CA1 synapses, when delivered either before tetanic s timulation of the perforant path or the Schaffer collaterals or long ( hours and days) after previously induced long-term potentiation had co mpletely decayed. However, when locus coeruleus or dorsal raphe stimul ation was delivered with the same parameters during a limited time (mi nutes and hours) after marked or even complete decay of tetanus-induce d long-term potentiation at perforant path-dentate gyrus or Schaffer c ollateral-CA1 synapses, the potentiation was partially or entirely res tored but never increased beyond the initial level of potentiation. In CA1, stimulation of ipsilateral and contralateral Schaffer collateral s demonstrated that the restoration of previously existing long-term p otentiation by dorsal raphe stimulation was input-specific, occurring, like tetanus-induced potentiation, only in the pathway which had prev iously been tetanized. These findings suggest that the noradrenergic l ocus coeruleus and the serotonergic dorsal raphe can influence not onl y induction, but also spontaneous decay of long-term potentiation in t he hippocampal formation. Since hippocampal long-term potentiation is thought to play a role in certain kinds of learning and memory, and as sociation of tetanic stimulation with activation of ascending neuromod ulatory systems is required for full expression of long-term potentiat ion, the restoration of hippocampal long-term potentiation by activati on of a neuromodulatory system alone may serve as a mechanism of assoc iative reminder which may underlie facilitation of memory retrieval af ter a period of forgetting, as has been observed in trained rats under similar conditions. (C) 1998 IBRO. Published by Elsevier Science Ltd.