mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity

M. Fendt; S. Schmid; D. R. Thakker; L. H. Jacobson; R. Yamamoto; K. Mitsukawa; R. Maier; F. Natt; D. Hüsken; P. H. Kelly; K. H. McAllister; D. Hoyer; H. Van Der Putten; J. F. Cryan; P. J. Flor

doi:10.1038/sj.mp.4002073

mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity

M. Fendt
, S. Schmid
, D. R. Thakker
, L. H. Jacobson
, R. Yamamoto
, K. Mitsukawa
, R. Maier
, F. Natt
, D. Hüsken
, P. H. Kelly
, K. H. McAllister
, D. Hoyer
, H. Van Der Putten
, J. F. Cryan
, P. J. Flor

Research output: Contribution to journal › Article › peer-review

Abstract

Formation and extinction of aversive memories in the mammalian brain are insufficiently understood at the cellular and molecular levels. Using the novel metabotropic glutamate receptor 7 (mGluR7) agonist AMN082, we demonstrate that mGluR7 activation facilitates the extinction of aversive memories in two different amygdala-dependent tasks. Conversely, mGluR7 knockdown using short interfering RNA attenuated the extinction of learned aversion. mGluR7 activation also blocked the acquisition of Pavlovian fear learning and its electrophysiological correlate long-term potentiation in the amygdala. The finding that mGluR7 critically regulates extinction, in addition to acquisition of aversive memories, demonstrates that this receptor may be relevant for the manifestation and treatment of anxiety disorders.

Original language	English
Pages (from-to)	970-979
Number of pages	10
Journal	Molecular Psychiatry
Volume	13
Issue number	10
DOIs	https://doi.org/10.1038/sj.mp.4002073
Publication status	Published - Oct 2008

Keywords

Anxiety
Fear learning
Glutamate
Metabotropic glutamate receptors

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10.1038/sj.mp.4002073

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Fendt, M., Schmid, S., Thakker, D. R., Jacobson, L. H., Yamamoto, R., Mitsukawa, K., Maier, R., Natt, F., Hüsken, D., Kelly, P. H., McAllister, K. H., Hoyer, D., Van Der Putten, H., Cryan, J. F., & Flor, P. J. (2008). mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity. Molecular Psychiatry, 13(10), 970-979. https://doi.org/10.1038/sj.mp.4002073

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title = "mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity",

abstract = "Formation and extinction of aversive memories in the mammalian brain are insufficiently understood at the cellular and molecular levels. Using the novel metabotropic glutamate receptor 7 (mGluR7) agonist AMN082, we demonstrate that mGluR7 activation facilitates the extinction of aversive memories in two different amygdala-dependent tasks. Conversely, mGluR7 knockdown using short interfering RNA attenuated the extinction of learned aversion. mGluR7 activation also blocked the acquisition of Pavlovian fear learning and its electrophysiological correlate long-term potentiation in the amygdala. The finding that mGluR7 critically regulates extinction, in addition to acquisition of aversive memories, demonstrates that this receptor may be relevant for the manifestation and treatment of anxiety disorders.",

keywords = "Anxiety, Fear learning, Glutamate, Metabotropic glutamate receptors",

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year = "2008",

month = oct,

doi = "10.1038/sj.mp.4002073",

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T1 - mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity

AU - Fendt, M.

AU - Schmid, S.

AU - Thakker, D. R.

AU - Jacobson, L. H.

AU - Yamamoto, R.

AU - Mitsukawa, K.

AU - Maier, R.

AU - Natt, F.

AU - Hüsken, D.

AU - Kelly, P. H.

AU - McAllister, K. H.

AU - Hoyer, D.

AU - Van Der Putten, H.

AU - Cryan, J. F.

AU - Flor, P. J.

PY - 2008/10

Y1 - 2008/10

N2 - Formation and extinction of aversive memories in the mammalian brain are insufficiently understood at the cellular and molecular levels. Using the novel metabotropic glutamate receptor 7 (mGluR7) agonist AMN082, we demonstrate that mGluR7 activation facilitates the extinction of aversive memories in two different amygdala-dependent tasks. Conversely, mGluR7 knockdown using short interfering RNA attenuated the extinction of learned aversion. mGluR7 activation also blocked the acquisition of Pavlovian fear learning and its electrophysiological correlate long-term potentiation in the amygdala. The finding that mGluR7 critically regulates extinction, in addition to acquisition of aversive memories, demonstrates that this receptor may be relevant for the manifestation and treatment of anxiety disorders.

AB - Formation and extinction of aversive memories in the mammalian brain are insufficiently understood at the cellular and molecular levels. Using the novel metabotropic glutamate receptor 7 (mGluR7) agonist AMN082, we demonstrate that mGluR7 activation facilitates the extinction of aversive memories in two different amygdala-dependent tasks. Conversely, mGluR7 knockdown using short interfering RNA attenuated the extinction of learned aversion. mGluR7 activation also blocked the acquisition of Pavlovian fear learning and its electrophysiological correlate long-term potentiation in the amygdala. The finding that mGluR7 critically regulates extinction, in addition to acquisition of aversive memories, demonstrates that this receptor may be relevant for the manifestation and treatment of anxiety disorders.

KW - Anxiety

KW - Fear learning

KW - Glutamate

KW - Metabotropic glutamate receptors

UR - https://www.scopus.com/pages/publications/51949091269

U2 - 10.1038/sj.mp.4002073

DO - 10.1038/sj.mp.4002073

M3 - Article

C2 - 17712315

AN - SCOPUS:51949091269

SN - 1359-4184

VL - 13

SP - 970

EP - 979

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 10

ER -

mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity

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Keywords

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