Differential roles of mGlu(7) and mGlu(8) in amygdala-dependent behavior and physiology.

TY - JOUR

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 -