Differential roles of mGlu7 and mGlu8 in amygdala-dependent behavior and physiology

Blocking Metabotropic Glutamate Receptor Subtype 7 (mGlu7) via the Venus Flytrap Domain (VFTD) Inhibits Amygdala Plasticity, Stress, and Anxiety-related Behavior

“…Electrophysiological Recordings-Preparation of acute brain slices containing the amygdala and subsequent field recordings were performed as described previously (14,45). Male C57BL/6 mice were used to test the dose dependence of XAP044, and male wild type (Grm7 ϩ/ϩ ) and knock-out (Grm7…”

“…EPM testing took place for 5 min In Vivo Testing, Fear Conditioning Paradigm-To measure the conditioned freezing response in mice, a computerized fear-conditioning system (TSE, Bad Homburg, Germany) was used as described previously (14,18,53). The cued-fear experiments were performed in two different contexts, A and B, that differed in visual, tactile, and olfactory cues.…”

“…We and others have focused on elucidating physiological roles of the group III receptor mGlu7, evolutionarily the most highly conserved mGlu subtype, suggesting it plays a key role in brain and synaptic function (7)(8)(9). Supporting a key role in brain physiology, mice lacking mGlu7 were shown to have deficits in amygdala-dependent fear learning and aversive behavior (10), reduced anxiety-and depression-like behavior (11)(12)(13)(14), and alterations in stress responses, including elevated production of brain-derived neurotrophic factor in the hippocampus (15). At the synaptic level, mGlu7 appears to regulate presynaptic GABA and L-glutamate release, which may contribute to mGlu7's regulating role in emotion-relevant brain circuitry (14,16,17).…”

“…Supporting a key role in brain physiology, mice lacking mGlu7 were shown to have deficits in amygdala-dependent fear learning and aversive behavior (10), reduced anxiety-and depression-like behavior (11)(12)(13)(14), and alterations in stress responses, including elevated production of brain-derived neurotrophic factor in the hippocampus (15). At the synaptic level, mGlu7 appears to regulate presynaptic GABA and L-glutamate release, which may contribute to mGlu7's regulating role in emotion-relevant brain circuitry (14,16,17). This role is also supported by findings in mice using siRNA-induced knockdown of mGlu7, inducing changes in innate anxiety, physiological and behavioral stress responses, and fear learning (18).…”

“…The first mGlu7-selective allosteric agonist N,NЈ-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082) has induced both anxiogenic-like (15,20), as well as anxiolytic-like and antidepressant-like behavioral responses in rodents (13,14,(21)(22)(23). However, the latter effects seem in contradiction with anxiolytic-and antidepressant-like behavioral changes observed in mice lacking mGlu7 or after siRNA-mediated knockdown.…”