A pathway−specific function for different AMPA receptor subunits in amygdala long−term potentiation and fear conditioning

The AMPA receptor subunit glutamate receptor 1 (GluR1 or GluR−A) contributes to amygdala−dependent emotional learning. It remains unclear, however, to what extent different amygdala pathways depend on GluR1, or other AMPA receptor subunits, for proper synaptic transmission and plasticity, and whether GluR1−dependent long−term potentiation (LTP) is necessary for auditory and contextual fear conditioning. Here, we dissected the role of GluR1 and GluR3 (GluR−C) subunits in AMPA receptor−dependent amygdala LTP and fear conditioning using knock−out mice (GluR1−/− and GluR3−/−). We found that, whereas LTP at thalamic inputs to lateral amygdala (LA) projection neurons and at glutamatergic synapses in the basal amygdala was completely absent in GluR1−/− mice, both GluR1 and GluR3 contributed to LTP in the cortico−LA pathway. Because both auditory and contextual fear conditioning were selectively impaired in GluR1−/− but not GluR3−/− mice, we conclude that GluR1−dependent synaptic plasticity is the dominant form of LTP underlying the acquisition of auditory and contextual fear conditioning, and that plasticity in distinct amygdala pathways differentially contributes to aversive conditioning