Enhanced Cortico-Amygdala Efficacy and Suppressed Fear in Absence of Rap1

Auditory fear conditioning, a model for fear learning, is thought to be mediated by synaptic changes in the cortical and thalamic inputs to the lateral amygdala (LA); however, the specific roles of both pathways are still debated. Here, we report that a CaMKII-alpha-Cre-mediated knock-out (KO) of the rap1a and rap1b genes impaired synaptic plasticity and increased basal synaptic transmission in the cortical but not thalamic input to the LA via presynaptic changes: increases in glutamate release probability and the number of glutamate quanta released by a single action potential. Moreover, KO mice with alterations in the cortico-LA pathway had impaired fear learning, which could be rescued by training with a more aversive unconditional stimulus. These results suggest that Rap1-mediated suppression of synaptic transmission enables plasticity in the cortico-amygdala pathway, which is required for fear learning with a moderately aversive unconditional stimulus.