Hl. Wang et al., CORTICOTROPIN-RELEASING FACTOR PRODUCES A LONG-LASTING ENHANCEMENT OFSYNAPTIC EFFICACY IN THE HIPPOCAMPUS, European journal of neuroscience, 10(11), 1998, pp. 3428-3437
We have previously demonstrated that intra-hippocampal injection of co
rticotrophin-releasing factor improved memory retention of an inhibito
ry avoidance learning in rats; while the electrophysiological effects
corticotrophin-releasing factor produces on hippocampal neurons are la
rgely uncharacterized. In the present study, we found that corticotrop
hin-releasing factor injected into the dentate gyrus of hippocampus pr
oduced a dose-dependent and long-lasting enhancement in synaptic effic
acy of these neurons, as measured by an increase in the amplitude and
slope of population excitatory postsynaptic potentials, as well as the
amplitude of population spike. The onset of corticotrophin-releasing
factor-induced potentiation was slow. It was observed approximately 40
-60 min after corticotrophin-releasing factor administration and laste
d for more than 5 h, This effect of corticotrophin-releasing factor wa
s blocked by pretreatment with the cyclase-adenosine-3,5-monophosphate
(cAMP) inhibitor Rp-adenosine-3,5-cyclic monophosphothiolate triethyl
amine (Rp-cAMPS) and partially blocked by the N-methyl-D-aspartate rec
eptor antagonist MK-801, Further, pretreatment with corticotrophin-rel
easing factor receptor antagonist dose-dependently diminished tetaniza
tion-induced long-term potentiation, and corticotrophin-releasing fact
or and tetanic stimuli had an additive effect on hippocampal neuron ex
citation. Moreover, direct injection of corticotrophin-releasing facto
r increased cAMP level in the dentate gyrus, These results together su
ggest that corticotrophin-releasing factor-induced potentiation simula
tes the late phase of tetanization-induced long-term potentiation and
cAMP seems to be the messenger mediating this effect. Moreover, cortic
otrophin-releasing factor-induced potentiation and long-term potentiat
ion may share some similar mechanisms, and corticotrophin-releasing fa
ctor is probably involved in the neural circuits underlying long-term
potentiation. Thus, corticotrophin-releasing factor may play an import
ant role in modulating synaptic plasticity in the hippocampus.