Fear Potentiated Startle Increases Phospholipase D (PLD) Expression/Activity and PLD-Linked Metabotropic Glutamate Receptor Mediated Post-Tetanic Potentiation in Rat Amygdala.

•In the present study, we report on presynaptic cellular mechanisms involved in fear potentiated startle long-term memory (FPS LTM) by examining downstream elements of metabotropic glutamate receptor (mGluR) signaling in the thalamic–lateral amygdala (Th–LA) synaptic pathway.•Following fear potentiated startle behavior (FPS) in rats, proteomic analyses identified a 30% decrease in amygdala aldolase A, that immunoprecipitated with amygdala anti-phospholipase D1 and D2 isoform (PLD1/2) antibodies.•Amygdala aldolase A has a reverse profile to the expression of PLD, a downstream target of mGluR signaling.•Paired (PA) group PLD expression and activity increased significantly, attesting that our hypothesis of increased PLD (in response to aldolase A reduction) is important for storage mechanisms of FPS LTM.•The fEPSPs during baseline and long-term potentiation (LTP) maintenance remain unaltered, but the PPR ratios in the PA group are reduced compared to the unpaired (UNP) confirming an increased release probability in FPS.•Neither inhibition nor stimulation of mGluR signaling via PLD affected the PA group PPR ratios suggesting that the increased probability of release coupled to the increased PLD activity may contribute to multiple vesicular release resulting in a constant PPR.•High frequency stimulation (HFS) recruits PLD signaling since the first field excitatory post synaptic potential (fEPSP) and post-tetanic potentiation (PTP) are affected following block of PLD–mGluR signaling.•These effects are similar to those mediated through mGluR7, which is co-immunoprecipitated with PLD in the PA group.•Finally, blocking PLD signaling upstream at mGluR level attenuated the associative memory mechanism underlying FPS response, underscoring the importance of PLD–mGluR in cue-induced anxiety and fear in emotional learning.