期刊
NEUROPHARMACOLOGY
卷 50, 期 2, 页码 154-164出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2005.08.002
关键词
metabotropic glutamate receptor; fear conditioning; long-term potentiation; electrophysiology; behavior; lateral amygdala; short-term plasticity; startle
The lateral amygdala plays an important role in emotional learning. Previous studies found that amygdaloid plasticity processes involve the activation of metabotropic glutamate receptors. In the present study we examined the effect of the highly specific mGluR8 agonist (S)-3,4-DCPG on conditioned fear in vivo measuring fear-potentiated startle. Both, acquisition and expression of conditioned fear were dose-dependently inhibited by (S)-3,4-DCPG injections into the amygdala. Since synaptic long-term potentiation in the lateral amygdala has been correlated with the acquisition of conditioned fear in rats, the effect of (S)-3,4-DCPG in vitro on synaptic transmission, short- and long-term plasticity in the lateral amygdala was evaluated in parallel. Patch clamp recordings in rat brain slices revealed that (S)-3,4-DCPG strongly attenuated synaptic transmission from sensory afferents. The lack of detectable effects on postsynaptic neurons and altered short-term plasticity indicate that (S)-3,4-DCPG acts at presynaptic sites. Long-term potentiation of thalamic afferent fiber synapses induced by a pairing protocol was slightly attenuated in the presence of (S)-3,4-DCPG, but long-term potentiation by tetanic afferent stimulation was inhibited. We conclude that mGluR8 activation is not specifically involved in long-term plasticity processes but that it rather provides a powerful inhibitory control of synaptic transmission within the lateral amygdala, with the ability to reduce activity in such a way that the expression and the acquisition of learned fear become strongly impaired in vivo. (c) 2005 Elsevier Ltd. All rights reserved.
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