13 research outputs found
Role of drug and food rewards in the selection and use of different forms of memory : interactions between the striatum and the hippocampus
No full textIl existe différents types de mémoire chez l’homme et l’animal. Chez les mammifères, on distingue principalement une mémoire relationnelle/spatiale reposant sur l’hippocampe et le cortex préfrontal, et une mémoire procédurale/indicée dépendante du striatum. Lors de nouveaux apprentissages, ces systèmes interagissent de manière coopérative et/ou compétitive en fonction de la nature de la tâche. S’il est connu que les émotions négatives et le niveau d’entraînement modulent ces interactions, peu de travaux ont étudié le rôle des récompenses dans la sélection et l’utilisation de ces deux formes principales de mémoire. Nous avons utilisé deux versions du test de discrimination spatiale dans un labyrinthe en Y afin de d’évaluer la mémoire spatiale d’une part, et la mémoire procédurale d’autre part. Nos résultats montrent que la stimulation pharmacologique du système de récompense par auto-injection de morphine au niveau de l’aire tegmentale ventrale (ATV), perturbe de manière spécifique l’apprentissage spatial reposant sur le fonctionnement hippocampo-préfrontal Ce déficit spatial s’accompagne d’une forte réduction de l’activité du facteur de transcription CREB (cAMP Response Element Binding) au sein de ce réseau. Au contraire, l’apprentissage indicé est préservé et l’activation de CREB est potentialisée par l’utilisation d’une récompense pharmacologique (injections de morphine). Nous mettons en évidence que la suractivation de la voie PKA/CREB, dans le striatum dorsal, est la cause de l’interférence observée lors de la formation de la mémoire spatiale. De plus, la stimulation répétée du système de récompense par la drogue lors de l’acquisition d’une stratégie indicée entraîne une persistance de l’activité réverbérante de la voie PKA/CREB dans le striatum dorsal. Cette persistance peut être révélée par l’utilisation préférentielle d’une stratégie indicée dans une nouvelle tâche ambigüe, le test de compétition en piscine de Morris. L’ensemble de ce travail éclaire, grâce aux effets différentiels de récompenses sensorielles et pharmacologiques sur l’apprentissage, la compréhension des interactions dynamiques entre les systèmes de mémoire. De plus, il suggère que l’hyperassociativité persistante consécutive à l’usage de drogue est à l’origine de déficits de type déclaratifs qui pourraient jouer un rôle clé dans l’installation d’un comportement addictif.There are different forms of memory proceeded in human’s and animal’s brain. At least two major systems can be defined. A spatial/declarative form of memory relies on the hippocampus and prefrontal cortex, and secondly, a more rigid, procedural/cued type of memory supported by striatal circuitry. Learning requires cooperative and/or competitive interactions between memory systems, depending on the nature of the task. It is well established that negative emotions and training modulate these interactions. However, little is known about the role of rewards on the selection and formation of these forms of memory.Using two versions (spatial or cue) of a Y-maze discrimination task, we show that drug reward, but not food reward, disrupts spatial learning while sparing the cued task. The spatial memory deficit relies on an decrease of CREB (cAMP Response Element Binding) activity within the hippocampus and the prefrontal cortex. Inhibition of the PKA/CREB signalling pathway restored spatial learning, suggesting that striatal overactivation of this pathway is responsible for the spatial memory deficit. The cued learning strategy elicits a strong CREB activitiy within the dorsal striatum which is further increased by morphine injections. We propose that drug-induced activation of the DA reward system induces abnormal reverberating activity of the PKA/CREB signalling pathway within the dorsal striatum, eventually leading to a preferential use of a striatum-dependent strategy during a new ambiguous learning task, the water maze competition task.In conclusion, our results points to a key role of rewards in the modulation of learning systems. Furthermore, we provide evidence that drug-induced striatal hyperactivity may underlie the declarative memory deficit reported here. This mechanism could represent an important early step toward the development of addictive behaviors by promoting conditioning to the detriment more flexible forms of memory
Role of drug and food rewards in the selection and use of different forms of memory : interactions between the striatum and the hippocampus
No full textIl existe différents types de mémoire chez l’homme et l’animal. Chez les mammifères, on distingue principalement une mémoire relationnelle/spatiale reposant sur l’hippocampe et le cortex préfrontal, et une mémoire procédurale/indicée dépendante du striatum. Lors de nouveaux apprentissages, ces systèmes interagissent de manière coopérative et/ou compétitive en fonction de la nature de la tâche. S’il est connu que les émotions négatives et le niveau d’entraînement modulent ces interactions, peu de travaux ont étudié le rôle des récompenses dans la sélection et l’utilisation de ces deux formes principales de mémoire. Nous avons utilisé deux versions du test de discrimination spatiale dans un labyrinthe en Y afin de d’évaluer la mémoire spatiale d’une part, et la mémoire procédurale d’autre part. Nos résultats montrent que la stimulation pharmacologique du système de récompense par auto-injection de morphine au niveau de l’aire tegmentale ventrale (ATV), perturbe de manière spécifique l’apprentissage spatial reposant sur le fonctionnement hippocampo-préfrontal Ce déficit spatial s’accompagne d’une forte réduction de l’activité du facteur de transcription CREB (cAMP Response Element Binding) au sein de ce réseau. Au contraire, l’apprentissage indicé est préservé et l’activation de CREB est potentialisée par l’utilisation d’une récompense pharmacologique (injections de morphine). Nous mettons en évidence que la suractivation de la voie PKA/CREB, dans le striatum dorsal, est la cause de l’interférence observée lors de la formation de la mémoire spatiale. De plus, la stimulation répétée du système de récompense par la drogue lors de l’acquisition d’une stratégie indicée entraîne une persistance de l’activité réverbérante de la voie PKA/CREB dans le striatum dorsal. Cette persistance peut être révélée par l’utilisation préférentielle d’une stratégie indicée dans une nouvelle tâche ambigüe, le test de compétition en piscine de Morris. L’ensemble de ce travail éclaire, grâce aux effets différentiels de récompenses sensorielles et pharmacologiques sur l’apprentissage, la compréhension des interactions dynamiques entre les systèmes de mémoire. De plus, il suggère que l’hyperassociativité persistante consécutive à l’usage de drogue est à l’origine de déficits de type déclaratifs qui pourraient jouer un rôle clé dans l’installation d’un comportement addictif.There are different forms of memory proceeded in human’s and animal’s brain. At least two major systems can be defined. A spatial/declarative form of memory relies on the hippocampus and prefrontal cortex, and secondly, a more rigid, procedural/cued type of memory supported by striatal circuitry. Learning requires cooperative and/or competitive interactions between memory systems, depending on the nature of the task. It is well established that negative emotions and training modulate these interactions. However, little is known about the role of rewards on the selection and formation of these forms of memory.Using two versions (spatial or cue) of a Y-maze discrimination task, we show that drug reward, but not food reward, disrupts spatial learning while sparing the cued task. The spatial memory deficit relies on an decrease of CREB (cAMP Response Element Binding) activity within the hippocampus and the prefrontal cortex. Inhibition of the PKA/CREB signalling pathway restored spatial learning, suggesting that striatal overactivation of this pathway is responsible for the spatial memory deficit. The cued learning strategy elicits a strong CREB activitiy within the dorsal striatum which is further increased by morphine injections. We propose that drug-induced activation of the DA reward system induces abnormal reverberating activity of the PKA/CREB signalling pathway within the dorsal striatum, eventually leading to a preferential use of a striatum-dependent strategy during a new ambiguous learning task, the water maze competition task.In conclusion, our results points to a key role of rewards in the modulation of learning systems. Furthermore, we provide evidence that drug-induced striatal hyperactivity may underlie the declarative memory deficit reported here. This mechanism could represent an important early step toward the development of addictive behaviors by promoting conditioning to the detriment more flexible forms of memory
Rôle des récompenses dans la sélection et l'utilisation de différentes formes de mémoire (interactions entre l'hippocampe et le striatum)
No full textIl existe différents types de mémoire chez l homme et l animal. Chez les mammifères, on distingue principalement une mémoire relationnelle/spatiale reposant sur l hippocampe et le cortex préfrontal, et une mémoire procédurale/indicée dépendante du striatum. Lors de nouveaux apprentissages, ces systèmes interagissent de manière coopérative et/ou compétitive en fonction de la nature de la tâche. S il est connu que les émotions négatives et le niveau d entraînement modulent ces interactions, peu de travaux ont étudié le rôle des récompenses dans la sélection et l utilisation de ces deux formes principales de mémoire. Nous avons utilisé deux versions du test de discrimination spatiale dans un labyrinthe en Y afin de d évaluer la mémoire spatiale d une part, et la mémoire procédurale d autre part. Nos résultats montrent que la stimulation pharmacologique du système de récompense par auto-injection de morphine au niveau de l aire tegmentale ventrale (ATV), perturbe de manière spécifique l apprentissage spatial reposant sur le fonctionnement hippocampo-préfrontal Ce déficit spatial s accompagne d une forte réduction de l activité du facteur de transcription CREB (cAMP Response Element Binding) au sein de ce réseau. Au contraire, l apprentissage indicé est préservé et l activation de CREB est potentialisée par l utilisation d une récompense pharmacologique (injections de morphine). Nous mettons en évidence que la suractivation de la voie PKA/CREB, dans le striatum dorsal, est la cause de l interférence observée lors de la formation de la mémoire spatiale. De plus, la stimulation répétée du système de récompense par la drogue lors de l acquisition d une stratégie indicée entraîne une persistance de l activité réverbérante de la voie PKA/CREB dans le striatum dorsal. Cette persistance peut être révélée par l utilisation préférentielle d une stratégie indicée dans une nouvelle tâche ambigüe, le test de compétition en piscine de Morris. L ensemble de ce travail éclaire, grâce aux effets différentiels de récompenses sensorielles et pharmacologiques sur l apprentissage, la compréhension des interactions dynamiques entre les systèmes de mémoire. De plus, il suggère que l hyperassociativité persistante consécutive à l usage de drogue est à l origine de déficits de type déclaratifs qui pourraient jouer un rôle clé dans l installation d un comportement addictif.There are different forms of memory proceeded in human s and animal s brain. At least two major systems can be defined. A spatial/declarative form of memory relies on the hippocampus and prefrontal cortex, and secondly, a more rigid, procedural/cued type of memory supported by striatal circuitry. Learning requires cooperative and/or competitive interactions between memory systems, depending on the nature of the task. It is well established that negative emotions and training modulate these interactions. However, little is known about the role of rewards on the selection and formation of these forms of memory.Using two versions (spatial or cue) of a Y-maze discrimination task, we show that drug reward, but not food reward, disrupts spatial learning while sparing the cued task. The spatial memory deficit relies on an decrease of CREB (cAMP Response Element Binding) activity within the hippocampus and the prefrontal cortex. Inhibition of the PKA/CREB signalling pathway restored spatial learning, suggesting that striatal overactivation of this pathway is responsible for the spatial memory deficit. The cued learning strategy elicits a strong CREB activitiy within the dorsal striatum which is further increased by morphine injections. We propose that drug-induced activation of the DA reward system induces abnormal reverberating activity of the PKA/CREB signalling pathway within the dorsal striatum, eventually leading to a preferential use of a striatum-dependent strategy during a new ambiguous learning task, the water maze competition task.In conclusion, our results points to a key role of rewards in the modulation of learning systems. Furthermore, we provide evidence that drug-induced striatal hyperactivity may underlie the declarative memory deficit reported here. This mechanism could represent an important early step toward the development of addictive behaviors by promoting conditioning to the detriment more flexible forms of memory.BORDEAUX1-Bib.electronique (335229901) / SudocSudocFranceF
Mesolimbic dopamine encodes prediction errors in a state-dependent manner
No full textMesolimbic dopamine encodes the benefits of a course of action. However, the value of an appetitive reward depends strongly on an animal’s current state. To investigate the relationship between dopamine, value, and physiological state, we monitored sub-second dopamine release in the nucleus accumbens core while rats made choices between food and sucrose solution following selective satiation on one of these reinforcers. Dopamine signals reflected preference for the reinforcers in the new state, decreasing to the devalued reward and, after satiation on food, increasing for the valued sucrose solution. These changes were rapid and selective, with dopamine release returning to pre-satiation patterns when the animals were re-tested in a standard food-restricted state. Such rapid and selective adaptation of dopamine-associated value signals could provide an important signal to promote efficient foraging for a varied diet
Heads for learning, tails for memory: Reward, reinforcement and a role of dopamine in determining behavioural relevance across multiple timescales
No full textDopamine has long been tightly associated with aspects of reinforcement learning and motivation in simple situations where there are a limited number of stimuli to guide behaviour and constrained range of outcomes. In naturalistic situations, however, there are many potential cues and foraging strategies that could be adopted, and it is critical that animals determine what might be behaviourally relevant in such complex environments. This requires not only detecting discrepancies with what they have recently experienced, but also identifying similarities with past experiences stored in memory. Here, we review what role dopamine might play in determining how and when to learn about the world, and how to develop choice policies appropriate to the situation faced. We discuss evidence that dopamine is shaped by motivation and memory and in turn shapes reward-based memory formation. In particular, we suggest that hippocampal-striatal-dopamine networks may interact to determine how surprising the world is and to either inhibit or promote actions at time of behavioural uncertainty
Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity
No full textMembrane Mineralocorticoid but not Glucocorticoid Receptors of the Dorsal Hippocampus Mediate the Rapid Effects of Corticosterone on Memory Retrieval
No full textInternational audienceThis study was aimed at determining the type of the glucocorticoid membrane receptors (mineralo or glucocorticoid receptors, MR or GR) in the dorsal hippocampus (dHPC) involved in the rapid effects of corticosterone or stress on memory retrieval. For that purpose, we synthesized Cort-3CMO-BSA conjugate (a high MW complex which cannot cross the cell membrane) totally devoid of free corticosterone, stable in physiological conditions. In a first experiment, we evidenced that an acute stress (electric footshocks) induced both a dHPC corticosterone rise measured by microdialysis and memory retrieval impairment on delayed alternation task. Both the endocrinal and cognitive effects of stress were blocked by metyrapone (a corticosterone synthesis inhibitor). In a second experiment, we showed that bilateral injections of either corticosterone or Cort-3CMO-BSA in dHPC 15 minutes before memory testing produced impairments similar to those resulting from acute stress. Furthermore, we showed that anisomycin (a protein synthesis inhibitor) failed to block the deleterious effect of Cort-3CMO-BSA on memory. In a third experiment, we evidenced that intra-hippocampal injection of RU-28318 (MR antagonist) but not of RU 38486 (GR antagonist) totally blocked the Cort-3CMO-BSA-induced memory retrieval deficit. In a fourth experiment, we demonstrated that RU-28318 administered 15 minutes before stress blocked the stress-induced memory impairments when behavioral testing occurred 15 but not 60 minutes after stress. Overall, the present study provides strong in vivo evidence that the dHPC membrane glucocorticoid receptors, mediating the rapid and non-genomic effects of acute stress on memory retrieval, are of MR but not GR type
Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity
No full textMorphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity
No full textDifferent parallel neural circuits interact and may even compete to process and store information: whereas stimulus–response (S–R) learning critically depends on the dorsal striatum (DS), spatial memory relies on the hippocampus (HPC). Strikingly, despite its potential importance for our understanding of addictive behaviors, the impact of drug rewards on memory systems dynamics has not been extensively studied. Here, we assessed long-term effects of drug- vs food reinforcement on the subsequent use of S–R vs spatial learning strategies and their neural substrates. Mice were trained in a Y-maze cue-guided task, during which either food or morphine injections into the ventral tegmental area (VTA) were used as rewards. Although drug- and food-reinforced mice learned the Y-maze task equally well, drug-reinforced mice exhibited a preferential use of an S–R learning strategy when tested in a water-maze competition task designed to dissociate cue-based and spatial learning. This cognitive bias was associated with a persistent increase in the phosphorylated form of cAMP response element-binding protein phosphorylation (pCREB) within the DS, and a decrease of pCREB expression in the HPC. Pharmacological inhibition of striatal PKA pathway in drug-rewarded mice limited the morphine-induced increase in levels of pCREB in DS and restored a balanced use of spatial vs cue-based learning. Our findings suggest that drug (opiate) reward biases the engagement of separate memory systems toward a predominant use of the cue-dependent system via an increase in learning-related striatal pCREB activity. Persistent functional imbalance between striatal and hippocampal activity could contribute to the persistence of addictive behaviors, or counteract the efficiency of pharmacological or psychotherapeutic treatments
