Synaptic modulation via basolateral amygdala on the rat hippocampus-medial prefrontal cortex pathway in fear extinction

Abstract

The present study elucidated the functional role of modulatory effects of basolateral amygdala (BLA) on synaptic transmission in the rat hippocampus - medial prefrontal cortex (mPFC) pathway, compared with the hippocampal dentate gyrus (DG). Exposure to conditioned fear stress (CFS) or prior BLA activation enhanced tetanus-induced long-term potentiation (LTP) in DG. A similar synaptic response was found by low frequency stimulation (LFS) prior to tetanus. In mPFC, they did not affect LTP, but prior BLA activation, as well as pretreatment with the N-methyl-D-aspartate (NMDA)-receptor antagonist MK-801 (0.1 mg/kg, i.p.), suppressed LFS-primed LTP. This BLA-mediated synaptic pattern was mimicked by synaptic changes observed in the fear extinction process; prior BLA activation suppressed the synaptic potentiation responsible for extinction retrieval and attenuated decreases in fear-related freezing behavior. These data suggest that LFS-primed LTP in mPFC is related to the neural basis of extinction. Extinction-related synaptic potentiation did not occur in a juvenile stress model that exhibited extinction deficit. In addition, LFS-primed LTP was suppressed in this model, which was reversed by the NMDA-receptor agonist d-cycloserine (15 mg/kg, i.p.). These findings suggest that modulatory effects of BLA on synaptic function in the hippocampus-mPFC pathway play a significant role in fear extinction in rats. © The Japanese Pharmacological Society.