mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity.
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.
Fendt
M
M
Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
Schmid
S
S
Thakker
D R
DR
Jacobson
L H
LH
Yamamoto
R
R
Mitsukawa
K
K
Maier
R
R
Natt
F
F
Hüsken
D
D
Kelly
P H
PH
McAllister
K H
KH
Hoyer
D
D
van der Putten
H
H
Cryan
J F
JF
Flor
P J
PJ
D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001559:Benzhydryl Compounds / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D014162:Transfection
D001559:Benzhydryl Compounds; C507346:N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride; D034741:RNA, Small Interfering; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D018698:Glutamic Acid