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

Glutamate transmission within the amygdala is crucial for amygdaloid plasticity and 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, the roles of mGlu7 and mGlu8 in different in vitro and in vivo paradigms of amygdaloid plasticity and behavior were investigated. We show that mGlu7-deficient but not mGlu8-deficient mice have attenuated long-term potention (LTP) within the amygdala. mGlu7-deficient mice express a general deficit in conditioned fear wheras in mGlu8-deficient mice, only contextual fear is strongly reduced . The mGlu7 agonist AMN082 reduces amygdaloid LTP and blocks the learning of conditioned fear after intra-amygdala injections. In contrast, the mGlu8 agonist DCPG decreased synaptic transmission within the amygdala but not LTP. Intra-amygdala injections of DCPG do only affect expression of contextual fear but not the learning and expression of cued fear. Taken together, these data revealed very different roles for amygdaloid mGlu7 and mGlu8 in the learning and expression of conditioned fear. Both receptors may be promising targets for the treatment of anxiety disorders; mGlu7 for anxiety disorders with pathological fear learning and mGlu8 for anxiety disorders with exaggerated contextual fear.