Differential roles of mGlu(7) and mGlu(8) in amygdala-dependent behavior and physiology.
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Differential roles of mGlu(7) and mGlu(8) in amygdala-dependent behavior and physiology. / Fendt, Markus; Imobersteg, Stefan; Peterlik, Daniel; Chaperon, Frédérique; Mattes, Catherine; Wittmann, Christina; Olpe, Hans-Rudolf; Mosbacher, Johannes; Vranesic, Ivo; van der Putten, Herman; McAllister, Kevin H; Flor, Peter J; Gee, Christine E.
In: NEUROPHARMACOLOGY, Vol. 72, 2013, p. 215-223.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Differential roles of mGlu(7) and mGlu(8) in amygdala-dependent behavior and physiology.
AU - Fendt, Markus
AU - Imobersteg, Stefan
AU - Peterlik, Daniel
AU - Chaperon, Frédérique
AU - Mattes, Catherine
AU - Wittmann, Christina
AU - Olpe, Hans-Rudolf
AU - Mosbacher, Johannes
AU - Vranesic, Ivo
AU - van der Putten, Herman
AU - McAllister, Kevin H
AU - Flor, Peter J
AU - Gee, Christine E
N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.
PY - 2013
Y1 - 2013
N2 - Glutamate transmission and synaptic plasticity in the amygdala are essential for the learning and expression of conditioned fear. Glutamate activates both ionotropic glutamate receptors and eight subtypes of metabotropic glutamate receptors (mGlu1-8). In the present study, we investigated the roles of mGlu7 and mGlu8 in amygdala-dependent behavior and synaptic plasticity. We show that ablation of mGlu7 but not mGlu8 attenuates long-term potentiation (LTP) at thalamo-lateral amygdala (LA) synapses where a strong association between LTP and learning has been demonstrated. mGlu7-deficient mice express a general deficit in conditioned fear whereas mGlu8-deficient mice show a dramatic reduction in contextual fear. The mGlu7 agonist AMN082 reduced thalamo-LA LTP and intra-amygdala administration blocked conditioned fear learning. In contrast, the mGlu8 agonist DCPG decreased synaptic transmission but not LTP at thalamo-LA synapses. Intra-amygdala DCPG selectively reduced the expression of contextual fear but did not affect the acquisition and expression of cued fear. Taken together, these data revealed very different roles for mGlu7 and mGlu8 in amygdala synaptic transmission, fear learning and its expression. These receptors seem promising targets for treating anxiety disorders with different underlying pathologies with exaggerated fear learning (mGlu7) or contextual fear (mGlu8).
AB - Glutamate transmission and synaptic plasticity in the amygdala are essential for the learning and expression of conditioned fear. Glutamate activates both ionotropic glutamate receptors and eight subtypes of metabotropic glutamate receptors (mGlu1-8). In the present study, we investigated the roles of mGlu7 and mGlu8 in amygdala-dependent behavior and synaptic plasticity. We show that ablation of mGlu7 but not mGlu8 attenuates long-term potentiation (LTP) at thalamo-lateral amygdala (LA) synapses where a strong association between LTP and learning has been demonstrated. mGlu7-deficient mice express a general deficit in conditioned fear whereas mGlu8-deficient mice show a dramatic reduction in contextual fear. The mGlu7 agonist AMN082 reduced thalamo-LA LTP and intra-amygdala administration blocked conditioned fear learning. In contrast, the mGlu8 agonist DCPG decreased synaptic transmission but not LTP at thalamo-LA synapses. Intra-amygdala DCPG selectively reduced the expression of contextual fear but did not affect the acquisition and expression of cued fear. Taken together, these data revealed very different roles for mGlu7 and mGlu8 in amygdala synaptic transmission, fear learning and its expression. These receptors seem promising targets for treating anxiety disorders with different underlying pathologies with exaggerated fear learning (mGlu7) or contextual fear (mGlu8).
KW - Amygdala
KW - Animals
KW - Conditioning (Psychology)
KW - Electric Stimulation
KW - Excitatory Amino Acid Agents
KW - Excitatory Postsynaptic Potentials
KW - Fear
KW - Long-Term Potentiation
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Receptors, Metabotropic Glutamate
U2 - 10.1016/j.neuropharm.2013.04.052
DO - 10.1016/j.neuropharm.2013.04.052
M3 - SCORING: Journal article
C2 - 23664812
VL - 72
SP - 215
EP - 223
JO - NEUROPHARMACOLOGY
JF - NEUROPHARMACOLOGY
SN - 0028-3908
ER -