Biphasic modulation of hippocampal plasticity by behavioral stress and basolateral amygdala stimulation in the rat

Abstract

Explicit memory may depend on the hippocampus, whereas the amygdala may be part of an emotional memory system. Priming stimulation of the basolateral group of the amygdala (BLA) resulted in an enhanced long-term potentiation (LTP) in the dentate gyrus (DG) to perforant path (PP) stimulation 30, 90, 150, and 180 min after high-frequency stimulation (HFS). Exposure of rats to a behavioral stress is reported to inhibit DG LTP. Because the amygdala is thought to mediate emotional responses, we examined the apparent discrepancy between the effects of behavioral stress induced 1 hr before HFS to the PP and of amygdala priming on hippocampal plasticity by stimulating the BLA 1 hr before HFS to the PP. The two delayed protocols inhibited the expression of LTP to PP stimulation, whereas priming the BLA immediately before HFS to the PP enhanced DG LTP. Moreover, exposure to the behavioral stress blocked the enhancing effects of BLA priming on LTP. We propose that the activation of the BLA (either by behavioral stress or by direct electrical stimulation) has a biphasic effect on hippocampal plasticity: an immediate excitatory effect and a longer-lasting inhibitory effect.

Fig. 1.

Schematic drawings of BLA electrode placements. After the completion of the experiment, the rats were given marking lesions of the BLA. Shown is a coronal view at position 2.8 mm posterior to bregma. Solid black circles indicate the locations.

Fig. 2.

Effects of behavioral stress on DG LTP. The increase in EPSP slope was measured as a percentage of baseline value immediately before the tetanus. Field potential recordings were taken 30, 90, 150, and 180 min after the application of HFS to the PP. In the HFS group (n = 10) HFS (3 sets of 10 trains, each one consists of 10 pulses at 100 Hz) was applied to the PP. The non-HFS group (n = 6) animals received only test stimulation over the same duration. In the stress groups (Platform,n = 9; UWT, n = 8) HFS was applied to the PP 1 hr after the exposure to the stressor. A comparison across the groups before HFS to the PP did not show a significant difference in the levels of LTP, indicating a similar baseline. There was a significant difference between the HFS group and the non-HFS group at all the times tested. Both stressors significantly inhibited LTP compared with the HFS group 30 min after HFS. However, from 90 min after HFS onward for the UWT group and from 150 min onward for the platform group, there was no significant difference (*significant difference between the HFS group and all the other groups; ^#significant difference between the HFS group and the non-HFS and the platform groups; ^$significant difference between the HFS and the non-HFS groups). In the HFS group the level of potentiation at 30 min after HFS was significantly different from zero, whereas the level of potentiation in the stressed animals was not.

Fig. 3.

Representative evoked potentials recorded from the DG before and after HFS to the PP. Evoked potentials immediately before HFS to the PP (A, D, G), at 30 min after HFS (B, E, H), and at 180 min (C, F, I) of HFS, platform, and BLA groups respectively, show the main effects of behavioral stress and of BLA priming on DG LTP. In the HFS group, LTP was significant both at 30 min (B) and 180 min (C). Behavioral stress temporally inhibited the expression of LTP at 30 min (E), but at 180 min (F) LTP was similar to control. In contrast, BLA priming enhanced the level of potentiation both at 30 min (H) and at 180 min (I).

Fig. 4.

BLA stimulation effects on DG LTP.A, In the BLA Priming group (n = 8), a stimulation to the BLA (10 trains of 5 pulses at 100 Hz) was applied 30 sec before HFS to the PP. In the1 hr-BLA group (n = 7), a stimulation to the BLA (10 trains of 5 pulses at 100 Hz) was applied 1 hr before HFS to the PP. Priming stimulation of the BLA significantly increased LTP compared with the HFS and the 1 hr-BLA groups at all times tested (*significant difference between the BLA priming group and the two other groups; ^#Significant difference between the HFS and the 1 hr-BLA groups). A comparison between the groups before HFS to the PP did not reveal a significant difference in the levels of the EPSP, indicating a similar baseline. B, The spaced activation of the BLA had no effect on baseline EPSP levels either at 1 min or at 1 hr after BLA stimulation (before HFS to the PP).

Fig. 5.

Changes in LTP after combined exposure to platform and BLA priming. Previous exposure to the platform completely blocked the enhancing effect of BLA priming on LTP (*significant difference between the BLA priming group and the other groups; ^#significant difference between the platform-BLA group and the HFS and BLA priming groups). A comparison between the groups before HFS to the PP did not reveal a significant difference in the levels of the EPSP, indicating a similar baseline.

Fig. 6.

Changes in LTP after combined exposure to UWT and BLA priming. Previous exposure to the UWT completely blocked the enhancing effect of BLA priming on LTP (*significant difference between the BLA priming group and the two other groups;^#significant difference between the UWT and the UWT-BLA groups). A comparison between the groups before HFS to the PP did not reveal a significant difference in the levels of the EPSP, indicating a similar baseline.

Fig. 7.

Present results in view of the proposed model (see Discussion for details). Two phases of hippocampal modulation by the BLA are suggested: a fast, short-living excitatory phase (triangle) and a slow, longer-lasting inhibitory phase (broken line). A, In animals that were exposed to the behavioral stressor, the attempt to induce LTP was performed 1 hr after the stressor and thus was under the influence of the second inhibiting phase. Hence, LTP was inhibited.B, Applying HFS to the PP in proximity to the stimulation of the BLA (PP1) resulted in high levels of LTP, because the hippocampus was under the influence of the first facilitatory phase. The stimulation of the PP 1 hr after BLA priming (PP2) was under the influence of the already active slow inhibitory phase. Thus, similarly to the effects of emotional stress, LTP was inhibited. C, When an animal was exposed to a stressor 1 hr before the stimulation of both the BLA and the PP, the hippocampus at the time of the HFS was under the influence of the second inhibitory phase, activated by the stressor. The inhibitory mechanism dominated the BLA-induced fast phase and inhibited the enhancing effects of BLA priming on LTP.