Bidirectional modulation of hippocampal long-term potentiation under stress and no-stress conditions in basolateral amygdala-lesioned and intact rats

Abstract

Hippocampal long-term potentiation (LTP) is widely considered as a cellular model for learning and memory formation. We have shown previously that protein synthesis-independent, early dentate gyrus (DG) LTP, lasting approximately 4-5 h, can be transformed into a late-LTP with a duration of > or = 24 h by a brief acute swim stress experience (high-stress condition). This reinforcement requires the activation of mineralocorticoid receptors and protein synthesis. The basolateral amygdala (BLA) is known to modulate glucocorticoid effects on the consolidation of spatial/contextual memory via a beta-adrenergic mechanism. Interestingly, hippocampal DG-LTP can also be indirectly modulated by beta-adrenergic and cholinergic/muscarinergic processes. Here, we show that the reinforcement of early-DG-LTP under high-stress conditions depends on the processing of novel spatial/contextual information. Furthermore, this reinforcement was blocked in BLA-lesioned animals compared with sham-operated and intact controls; however, it was not dependent on beta-adrenergic or cholinergic/muscarinergic receptor activation. In contrast, under low-stress conditions, the induction of late-LTP in BLA-lesioned animals is facilitated, and this facilitation, again, was dependent on beta-adrenergic activation. The data suggest that DG-LTP maintenance can be influenced by the BLA through different mechanisms: a short-lasting corticosterone-dependent and beta-adrenergic-independent mechanism and a long-lasting mechanism that facilitated hippocampal beta-adrenergic mechanisms.

Figure 1.

Schema of the experimental design for LTP experiments (left) and blood sampling (right). A, Intact animals; B, sham-operated animals; C, BLA-lesioned animals; D, pretrained animals; E, naive animals.

Figure 2.

BLA-lesioned (n = 6) animals showed a depotentiation and impairment of LTP under stress conditions compared with sham-operated animals (n = 9; A), whereas under no stress conditions, LTP was facilitated (weak lesion; n = 8) after a weak tetanus compared with controls (weak sham; n = 6; B). No potentiation beyond that elicited by a weak tetanus could be induced by a strong tetanus (strong lesion; n = 6) in lesioned animals (B). The mean and SEM of population-spike amplitudes as percentages from baseline values are shown. Bottom, Representative analog traces at the time points indicated for sham-operated and lesioned animals as well as a scheme of the largest and smallest extent of BLA lesions are shown.

Figure 3.

No difference in granule cell excitability, as indicated by the input/output curves (A) and the plot of EPSP against the PSA (B), could be noted between sham-operated (n = 15) and lesioned (n = 16) animals. The spontaneous granule cell activity is similar in both groups (lesion, n = 13; sham, n = 11), as indicated by the spectral power (C; left, top) and after treatment with timolol (C; left, bottom) (timolol, n = 6; saline, n = 7). In the middle, power spectra for lesioned animals before (top) and 20 min after (bottom) injection of timolol are shown. The related EEG recordings are shown at the right.

Figure 4.

Applicaton of atropine (A), a muscarinergic/cholinergic antagonist (n = 8; vehicle, n = 8), as well as timolol (n = 7; vehicle, n = 6), a β-adrenergic antagonist (B), could not prevent LTP reinforcement after a 2 min swim. The same amount of timolol (n = 8; vehicle, n = 8) was sufficient to prevent the induction of a late-LTP by a strong tetanus under no-stress condition (C). The concentration of timolol used did not affect basal transmission (n = 7), as well as early-LTP (D; vehicle, n = 7; timolol, n = 5), but blocked the facilitation of LTP in lesioned animals (E; vehicle, n = 8; timolol, n = 7). The mean and SEM of population-spike amplitudes as percentages from baseline values are shown. The insets are representative analog traces at the time points indicated for lesioned animals treated with vehicle or timolol.

Figure 5.

Pretraining prevented LTP reinforcement by swim stress (A). Pretrained animals (n = 6) showed no prolonged maintenance of LTP compared with controls (n = 10). B, Pretrained animals (n = 8) showed increased path lengths and a higher mean swim speed but decreased amounts of thigmotaxis compared with naive animals (n = 8) during a 2 min swim. The insets show representative swimming paths of a naive animal and for the initial trial (pretrial 1) and the test trial of a pretrained animal.

Figure 6.

All stressed groups show a similar and significant increase in serum corticosterone levels 15 min after swimming compared with unstressed animals. This increase is independent of being naive (intact stress) or being pretrained (intactp stress). No difference between stress levels or basal levels of corticosterone could be noted between sham-operated and lesioned animals (stress: intact, n = 8; pretrained, n = 8; sham, n = 4; lesioned, n = 9; base levels: intact, n = 6; sham, n = 3; lesioned, n = 10). Error bars represent means and SEM of serum corticosterone.