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 (mGlu 1–8 ). In the present study, we investigated the roles of mGlu 7 and mGlu 8 in amygdala-dependent behavior and synaptic plasticity. We show that ablation of mGlu 7 but not mGlu 8 attenuates long-term potentiation (LTP) at thalamo-lateral amygdala (LA) synapses where a strong association between LTP and learning has been demonstrated. mGlu 7 -deficient mice express a general deficit in conditioned fear whereas mGlu 8 -deficient mice show a dramatic reduction in contextual fear. The mGlu 7 agonist AMN082 reduced thalamo-LA LTP and intra-amygdala administration blocked conditioned fear learning. In contrast, the mGlu 8 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 mGlu 7 and mGlu 8 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 (mGlu 7 ) or contextual fear (mGlu 8 ).