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Tiba, P. A.

Publications and source records attributed to Tiba, P. A..

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Corticosterone differentially modulates time-dependent fear generalization following mild or moderate fear conditioning training in rats

Stressful and emotionally arousing experiences create strong memories that seem to lose specificity over time. It is uncertain, however, how the stress system contributes to the phenomenon of time-dependent fear generalization. Here, we investigated whether post-training corticosterone (CORT-HBC) injections, given after different training intensities, affect contextual fear memory specificity at several time points. We trained male Wistar rats on the contextual fear conditioning (CFC) task using two footshock intensities (mild CFC, 3 footshocks of 0.3 mA, or moderate CFC, 3x 0.6 mA) and immediately after the training session we administered CORT-HBC systemically. We first tested the animals in a novel context and then in the training context at different intervals following training (2, 14, 28 or 42 days). By measuring freezing in the novel context and then contrasting freezing times shown in both contexts, we inferred contextual fear generalization for each rat, classifying them into Generalizers or Discriminators. Following mild CFC training, the glucocorticoid injection promoted an accurate contextual memory at the recent time point (2 days), and increase the contextual memory accuracy 28 days after training. In contrast, after the moderate CFC training, CORT-HBC facilitated contextual generalization at 14 days, compared to the control group that maintained contextual discrimination at this timepoint. For this training intensity, however, CORT-HBC did not have any effect on recent memory specificity. These findings indicate that treatment with CORT-HBC immediately after the encoding of mild or moderately arousing experiences may differentially modulate memory consolidation and time-dependent fear generalization. HIGHLIGHTS- Rats were trained in a contextual fear task and tested for fear generalization. - Corticosterone (CORT) injected after a mild training promoted accuracy up to 28 days. - CORT injected after a moderate training facilitated time-dependent fear generalization.

animal behavior and cognition

Relationship between footshock intensity, post-training corticosterone release and contextual fear memory specificity over time

Overgeneralized fear has long been implicated in generalized anxiety and post-traumatic stress disorder, however, time-dependent mechanisms underlying memory retrieval are still not completely understood. Previous studies have revealed that stronger fear conditioning training protocols are associated with both increased post-training corticosterone (CORT) levels and fear responses at later retrieval tests. Here we used discriminative contextual fear conditioning (CFC) to investigate the relationship between post-training CORT levels and memory specificity in different retrieval timepoints. Wistar rats were exposed to CFC training with increasing footshock intensities (0.3, 0.6 or 1.0mA) and had their blood collected 30 min afterwards to measure post-training plasma CORT. After 2, 14 or 28 days, rats were tested for memory specificity either in the training or in the novel context. Regression analysis was used to verify linear and non-linear interactions between CORT levels and freezing. Higher footshock intensities increased post-training CORT levels and freezing times during tests in all timepoints. Moreover, stronger trainings elicited faster memory generalization, which was associated with higher CORT levels during memory consolidation. The 0.3mA training maintained memory specificity up to 28 days. Additionally, linear regressions suggest that the shift from specific to generalized memories is underway at 14 days after training. These results are consistent with the hypotheses that stronger training protocols elicit a faster generalization rate, and that this process is associated with increased post-training CORT release.\n\nHIGHLIGHTSStronger contextual fear conditioning (CFC) elicits higher plasma corticosterone (CORT).\n\nStrong CFC and high CORT levels increase the rate of memory generalization.\n\nWeak CFC and low CORT levels retain memory specificity up to 28 days.\n\nPost-training plasma CORT is linearly associated with remote generalized fear.

animal behavior and cognition