Vl. Ezrokhi et al., RESTORATION OF DECAYING LONG-TERM POTENTIATION IN THE HIPPOCAMPAL-FORMATION BY STIMULATION OF NEUROMODULATORY NUCLEI IN FREELY MOVING RATS, Neuroscience, 88(3), 1999, pp. 741-753
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.