Exposure to acute stress blocks the induction of long-term potentiation of the amygdala-prefrontal cortex pathway in vivo

Abstract

In recent years, attention has been given to the interaction between the emotional state of the animal and its ability to learn and remember. Studies into the neural mechanisms underlying these interactions have focused on stress-induced synaptic plasticity impairments in the hippocampus. However, other brain areas, including the amygdala and the prefrontal cortex (PFC), have been implicated in relation to stress-mediated effects on memory. The present study examined whether stress, which impairs hippocampal long-term potentiation (LTP), also affects LTP of the basolateral amygdala (BLA)-PFC pathway in vivo. We first confirmed that the stress protocol we used, i.e., the elevated platform stress, was effective in blocking LTP in the CA1 area of the hippocampus. We then characterized activity and established the ability to induce LTP at the BLA-PFC pathway. Finally, we examined the effects of an exposure to the elevated platform stress on the ability to induce LTP in this pathway. The results indicate that, at the same time when LTP is blocked in the hippocampus, it is also inhibited in the BLA-medial PFC pathway. These results call for a shift from a focused attention on the effects of stress on plasticity in the hippocampus to a system level approach that emphasizes the possible modification of interactions between relevant brain areas after an exposure to a stressful experience.

Figure 1.

Top, The stimulating electrode in the BLA. Bottom, Schematic diagram representing the location of the recording electrode in the prelimbic area. Solid black circles indicate the locations.

Figure 2.

TBS induces LTP in the mPFC. This LTP is blocked by the NMDA receptor antagonist CPP. The increase in EPSP amplitude (LTP) was measured as a percentage of baseline value immediately before TBS to the BLA. Delivering TBS to the BLA induced a robust and long-lasting increase of the amplitude of the evoked field potential in the mPFC, reflecting the potentiation of the amygdala–PFC pathway. This group of LTP was significantly different from the low-frequency stimulation (Low Freq) controls at all the time points after TBS (F_(5,7) = 5.149; p < 0.05). The level of potentiation in the LFS group was not significantly different from 100% at any time point. The injection of the competitive NMDA receptor antagonist (10 mg/kg) CPP 45 min before TBS significantly inhibited the induction of LTP; no increase of the EPSP amplitude was observed in the CPP-treated rats at any time point [t test for difference from baseline (100%); t₍₄₎ < 1; n = 5; NS]. Top left corner, Representative field potentials in the mPFC evoked during BLA stimulation immediately before and 90 min after TBS. The baseline (thin line) and the potentiated response are superimposed and are averages of 20 evoked responses each. Calibration: 0.2 mV, 10 msec.

Figure 3.

Behavioral stress impairs amygdala–PFC LTP. Thirty minutes of exposure to stress significantly inhibited the ability of TBS to induce LTP in the PFC for all of the time points tested [t test for difference from baseline (100%); t₍₇₎ < 1; NS for all time points].