RESUMO
Long-term memory (LTM) can be induced by repeated spaced training trials. Using the weak inhibitory avoidance (wIA) task, we showed that one wIA session does not lead to a 24-h LTM, whereas two identical wIA sessions spaced by 15 min to 6 h induce a 24-h LTM. This LTM promotion depends both on hippocampal protein synthesis and the activity of several kinases. In agreement with the behavioral tagging (BT) hypothesis, our results suggest that the two training sessions induce transient learning tags and lead, via a cooperative effect, to the synthesis of plasticity-related proteins (PRPs) that become available and captured by the tag from the second session. Although ERKs1/2 are needed for PRPs synthesis and CaMKs are required for tag setting, PKA participates in both processes. We conclude that the BT mechanism accounts for the molecular constraints underlying the classic effect of spaced learning on LTM formation.
RESUMO
The behavioral tagging (BT) hypothesis postulates that a weak learning experience, which only induces short-term memory, may benefit from another event that provides plasticity-related proteins (PRPs) to establish a long-lasting memory. According to BT, the weak experience sets a transient learning tag at specific activated sites, and its temporal and spatial convergence with the PRPs allows the long-term memory (LTM) formation. In this work, rats were subjected to a weak inhibitory avoidance (IAw) training and we observed that acute stress (elevated platform, EP) experienced 1 hr before IAw promoted IA-LTM formation. This effect was dependent on glucocorticoid-receptor activity as well as protein synthesis in the dorsal hippocampus. However, the same stress has negative effects on IA-LTM formation when training is strong, probably by competing for necessary PRPs. Furthermore, our experiments showed that EP immediately after training did not impair the setting of the learning tag and even facilitated IA-LTM formation. These findings reveal different impacts of a given acute stressful experience on the formation of an aversive memory that could be explained by BT processes.
Assuntos
Memória de Longo Prazo , Memória de Curto Prazo , Animais , Aprendizagem da Esquiva , Hipocampo , Aprendizagem , Ratos , Ratos WistarRESUMO
The superiority of spaced over massed learning is an established fact in the formation of long-term memories (LTM). Here we addressed the cellular processes and the temporal demands of this phenomenon using a weak spatial object recognition (wSOR) training, which induces short-term memories (STM) but not LTM. We observed SOR-LTM promotion when two identical wSOR training sessions were spaced by an inter-trial interval (ITI) ranging from 15 min to 7 h, consistently with spaced training. The promoting effect was dependent on neural activity, protein synthesis and ERKs1/2 activity in the hippocampus. Based on the "behavioral tagging" hypothesis, which postulates that learning induces a neural tag that requires proteins to induce LTM formation, we propose that retraining will mainly retag the sites initially labeled by the prior training. Thus, when weak, consecutive training sessions are experienced within an appropriate spacing, the intracellular mechanisms triggered by each session would add, thereby reaching the threshold for protein synthesis required for memory consolidation. Our results suggest in addition that ERKs1/2 kinases play a dual role in SOR-LTM formation after spaced learning, both inducing protein synthesis and setting the SOR learning-tag. Overall, our findings bring new light to the mechanisms underlying the promoting effect of spaced trials on LTM formation.
Assuntos
Comportamento Animal , Hipocampo/fisiologia , Memória de Longo Prazo/fisiologia , Memória de Curto Prazo/fisiologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Memória Espacial/fisiologia , Animais , Condicionamento Psicológico , Ativação Enzimática , Masculino , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Biossíntese de Proteínas , Ratos , Ratos WistarRESUMO
Stress is known to have a critical impact on memory processes. In the present work, we focus on the effects of an acute stress event closely associated to an unrelated learning task. Here, we show that acute stress (elevated platform [EP] session) experienced 1 hr after a weak spatial object recognition (SOR) training, which only induces a short-term memory (STM), promoted the formation of SOR-long term memory (SOR-LTM) in rats. The effect induced by stress was dependent on the activation of glucocorticoid- and mineralocorticoid-receptors, brain-derived neurotrophic factor (BDNF) and protein synthesis in the dorsal hippocampus. In contrast, EP after a strong SOR impaired SOR-LTM probably by interfering with the use of necessary resources. Moreover, we show that the EP session before training induced anterograde interference, which it was not reversed by a subsequent exposure to an open field. Our findings provide novel insights into the impact of stress on LTM formation in rodents and they are discussed under the behavioral analogue of the synaptic tagging and capture hypothesis.