title: Differential roles of mGlu(7) and mGlu(8) in amygdala-dependent behavior and physiology.
abstract: 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).
authors.affiliation: Novartis Institutes for BioMedical Research, Neuroscience DA, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland. markus.fendt@med.ovgu.de
authors.forename: Markus
authors.initials: M
authors.lastname: Fendt
authors.forename: Stefan
authors.initials: S
authors.lastname: Imobersteg
authors.forename: Daniel
authors.initials: D
authors.lastname: Peterlik
authors.forename: Frédérique
authors.initials: F
authors.lastname: Chaperon
authors.forename: Catherine
authors.initials: C
authors.lastname: Mattes
authors.forename: Christina
authors.initials: C
authors.lastname: Wittmann
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Olpe
authors.forename: Johannes
authors.initials: J
authors.lastname: Mosbacher
authors.forename: Ivo
authors.initials: I
authors.lastname: Vranesic
authors.forename: Herman
authors.initials: H
authors.lastname: van der Putten
authors.forename: Kevin H
authors.initials: KH
authors.lastname: McAllister
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Flor
authors.forename: Christine E
authors.initials: CE
authors.lastname: Gee
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001703:Biophysics; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005239:Fear / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009068:Movement / Q000187:drug effects / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018683:Excitatory Amino Acid Agents; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7; C111435:metabotropic glutamate receptor 8