Etude de l'évolution et du rappel des représentations mnésiques chez le rat

L'étude de l'évolution des stratégies comportementales au cours d'un apprentissage a mis en évidence que, dans une épreuve de labyrinthe en T, les rats choisissent indifféremment une stratégie spatiale ou égocentrée en début d'apprentissage, puis adoptent une stratégie égocentrée. Des lésions, du CPFm ventral conduisent au maintien d'un choix équilibré des stratégies. Des lésions du striatum dorsal favorisent l'utilisation précoce d'une stratégie égocentrée. Notre étude a montré que l'évolution des stratégies dépend de l'épreuve, de structures cérébrales comme le cortex PL-IL, mais pas de l'intégrité des boucles cortico-striatales. L'étude du mécanisme d'action des indices de rappel a montré que, dans une épreuve d'évitement en discrimination lumineuse, la présentation de lac lumière à 1 jour ou du contexte expérimental à 21 jours améliore les performances de rétention et s'accompagne d'une activation de l'axe corticotrope, dont le blocage par un antagoniste CRF1 bloque l'effet facilitateur de la lumière. La naloxone (antagoniste opiacé), qui bloque les effets comportementaux des indices de rappel, diminue spécifiquement les taux d'ACTH après exposition à un indice de rappel. Ces données indiquent un lien de causalité notamment entre le CRF et les indices de rappel, qui pourrait s'exercer au niveau de l'amygdale. L'étude des bases structurales a révélé que des lésions du CPFm annihilent tout effet des indices de rappel. Au sein du SD, seule la partie latérale est impliquée dans les processus de rappel. La présentation d'un indice de rappel lumineux diminue les taux de PhosphoERK dans le CPF et l'amygdale, indiquant que une implication des voies des MAPK. Ces données permettent d'établir un schéma explicatif possible des mécanismes d'action mis enjeu lors de la présentation d'un indice de rappel. Il semble, comme chez l'homme, que deux formes de rappel puissent être mises en évidence par la nature des processus de recherche et les structures cérébrales impliqués.Rats learning a T-maze task initially use a spatial or egocentric strategy but progressively change over time to predominantly an egocentric approach. Lesions to the ventral part of the medial prefrontal cortex (mPFC) block this change of strategy, such that both strategies are equally chosen even after overtraining, whereas, lesions to the dorsal striatum lead to an early choice of the egocentric strategy. Our study shows that the change of strategy depends on the task, and on brain structures such as the PL-IL cortex, but not on cortico-striatal circuits. Study of mechanisms underlying the effects of retrieval cues indicate that, in a brightness discrimination avoidance task, exposure to the light discriminative stimulus or to the experimental context enhances retention performance when the test is delivered 1 and 21 days, respectively, after training. This behavioural effect is accompanied by an activation of the stress axis, and interruption by a CRF1 antagonist blocks the facilitative effect of light. Naloxone (an opoid antagonist) disrupts the behavioural effect of retrieval cues and decreases significantly the ACTH levels after exposure to the retrieval cue. These data indicate a causal link between CRF and retrieval cues that could exist in the amygdala. The mPFC was implicated~ whereby lesions of the area block the facilitative effect of the retrieval cues. A functional dissociation is observed in the dorsal striatum: only the lateral part being involved in retrieval processes. Exposure to the light decreases the PhosphoERK levels in the PFC and in the amygdala, indicating an involvement of the MAPK cascades. These data suggest explicit circuits underlying the processes involved following exposure to retrieval cues. It appears that, as in humans, two forms of retrieval can be observed, dependent upon the test used and brain structures involved.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Exposure to retrieval cues improves retention performance and induces changes in ACTH and corticosterone release

Memory retrieval can be facilitated by pretest exposure to cues associated with the original training. The present series of experiments was aimed at investigating whether the effectiveness of the retrieval cues might be due to their emotional value and thus be associated to a particular pattern of activation of stress systems. Therefore, the effects of exposing rats to different cueing conditions were investigated both on retention performance and on the level of different stress hormones (ACTH, corticosterone and glucose; the latter as an indirect index of adrenergic/sympathetic nervous system activation). Rats trained in a brightness avoidance discrimination task exhibited an enhancement of the retention performance following exposure to the light discriminative stimulus when delivered 1-day after training and not after 21 days, while exposure to contextual cues led to opposite effects on the retention performance, confirming our previous results. Analyses of the level of stress hormones at the time of testing indicated that when the retrieval cues were effective at the behavioral level, cued rats exhibited higher ACTH plasmatic levels than controls, but did not differ in their glucose or corticosterone levels. Further experiments showed that one day after training, both ACTH and corticosterone levels were elevated in light-cued rats if hormone samples were taken 15 min after cueing. These results show that exposure to an effective retrieval cue is accompanied by the activation of the hypothalamus-pituitary-adrenal axis. The possible involvement of the Corticotropin Releasing Factor at the level of the hypothalamus and amygdala (particularly the central nucleus) on the facilitating effect on retention performance following exposure to aversive training-associated cues is discussed. The present results strengthen the notion that emotion can interact with retrieval processes