Rôle d'un circuit hippocampo-cortico-thalamique dans les processus de mémoire spatiale chez le rat

This thesis aimed to investigate the role of a circuit encompassing the hippocampus (Hip), the medial prefrontal cortex (mPFC) and the reuniens and rhomboid nuclei (ReRh) of the thalamus in cognitive processes underlying spatial memory in rats. We first showed that ReRh nuclei may be involved in systemic consolidation, a mechanism necessary for memory persistence and requiring hippocampal-cortical interactions. We confirmed these findings in a second study showing that mPFC neuronal activity during recall of a remote spatial memory depends on ReRh thalamic nuclei. We also showed the involvement of the ReRh nuclei in a mnemonic task requiring the use of both spatial information (dependent on the Hip) and behavioral flexibility (involving the mPFC). Finally, we found a role of the mPFC in the recall of recent spatial memory. Taken together, these results highlight the importance of a hippocampo-cortico-thalamic circuit in the processing and persistence of spatial information in the Rat.Cette thèse avait pour objectif d’étudier le rôle du circuit composé de l’hippocampe (Hip), du cortex préfrontal médian (mPFC) et des noyaux reuniens et rhomboïde (ReRh) du thalamus dans les processus cognitifs qui sous-tendent la mémoire spatiale chez le Rat. Nous avons montré que les noyaux ReRh pourraient être impliqués dans la consolidation systémique, mécanisme nécessaire à la persistance des souvenirs et nécessitant un dialogue hippocampo-cortical. Nous avons mis en évidence que l’activité neuronale du mPFC durant le rappel d’une mémoire ancienne dépend des noyaux ReRh, ainsi que l’implication de ces noyaux dans une tâche de mémoire spatiale (dépendante de l’Hip) nécessitant une flexibilité comportementale (impliquant le mPFC). Enfin, nous avons montré un rôle du mPFC dans le rappel d’une mémoire spatiale récente. Ces résultats mettent en évidence l’importance de ce circuit hippocampo-cortico-thalamique dans le traitement et la persistance des informations spatiales chez le Rat

Role of a hippocampal-cortical-thalamic circuit in spatial memory processes in the rat

Cette thèse avait pour objectif d’étudier le rôle du circuit composé de l’hippocampe (Hip), du cortex préfrontal médian (mPFC) et des noyaux reuniens et rhomboïde (ReRh) du thalamus dans les processus cognitifs qui sous-tendent la mémoire spatiale chez le Rat. Nous avons montré que les noyaux ReRh pourraient être impliqués dans la consolidation systémique, mécanisme nécessaire à la persistance des souvenirs et nécessitant un dialogue hippocampo-cortical. Nous avons mis en évidence que l’activité neuronale du mPFC durant le rappel d’une mémoire ancienne dépend des noyaux ReRh, ainsi que l’implication de ces noyaux dans une tâche de mémoire spatiale (dépendante de l’Hip) nécessitant une flexibilité comportementale (impliquant le mPFC). Enfin, nous avons montré un rôle du mPFC dans le rappel d’une mémoire spatiale récente. Ces résultats mettent en évidence l’importance de ce circuit hippocampo-cortico-thalamique dans le traitement et la persistance des informations spatiales chez le Rat.This thesis aimed to investigate the role of a circuit encompassing the hippocampus (Hip), the medial prefrontal cortex (mPFC) and the reuniens and rhomboid nuclei (ReRh) of the thalamus in cognitive processes underlying spatial memory in rats. We first showed that ReRh nuclei may be involved in systemic consolidation, a mechanism necessary for memory persistence and requiring hippocampal-cortical interactions. We confirmed these findings in a second study showing that mPFC neuronal activity during recall of a remote spatial memory depends on ReRh thalamic nuclei. We also showed the involvement of the ReRh nuclei in a mnemonic task requiring the use of both spatial information (dependent on the Hip) and behavioral flexibility (involving the mPFC). Finally, we found a role of the mPFC in the recall of recent spatial memory. Taken together, these results highlight the importance of a hippocampo-cortico-thalamic circuit in the processing and persistence of spatial information in the Rat

Role of a hippocampal-cortical-thalamic circuit in spatial memory processes in the rat

Cette thèse avait pour objectif d’étudier le rôle du circuit composé de l’hippocampe (Hip), du cortex préfrontal médian (mPFC) et des noyaux reuniens et rhomboïde (ReRh) du thalamus dans les processus cognitifs qui sous-tendent la mémoire spatiale chez le Rat. Nous avons montré que les noyaux ReRh pourraient être impliqués dans la consolidation systémique, mécanisme nécessaire à la persistance des souvenirs et nécessitant un dialogue hippocampo-cortical. Nous avons mis en évidence que l’activité neuronale du mPFC durant le rappel d’une mémoire ancienne dépend des noyaux ReRh, ainsi que l’implication de ces noyaux dans une tâche de mémoire spatiale (dépendante de l’Hip) nécessitant une flexibilité comportementale (impliquant le mPFC). Enfin, nous avons montré un rôle du mPFC dans le rappel d’une mémoire spatiale récente. Ces résultats mettent en évidence l’importance de ce circuit hippocampo-cortico-thalamique dans le traitement et la persistance des informations spatiales chez le Rat.This thesis aimed to investigate the role of a circuit encompassing the hippocampus (Hip), the medial prefrontal cortex (mPFC) and the reuniens and rhomboid nuclei (ReRh) of the thalamus in cognitive processes underlying spatial memory in rats. We first showed that ReRh nuclei may be involved in systemic consolidation, a mechanism necessary for memory persistence and requiring hippocampal-cortical interactions. We confirmed these findings in a second study showing that mPFC neuronal activity during recall of a remote spatial memory depends on ReRh thalamic nuclei. We also showed the involvement of the ReRh nuclei in a mnemonic task requiring the use of both spatial information (dependent on the Hip) and behavioral flexibility (involving the mPFC). Finally, we found a role of the mPFC in the recall of recent spatial memory. Taken together, these results highlight the importance of a hippocampo-cortico-thalamic circuit in the processing and persistence of spatial information in the Rat

Ventral midline thalamus is necessary for hippocampal place field stability and cell firing modulation

International audienceThe reuniens (Re) and rhomboid (Rh) nuclei of the ventral midline thalamus are reciprocally connected with the hippocampus (Hip) andthe medial prefrontal cortex (mPFC). Growing evidence suggests that these nuclei might play a crucial role in cognitive processesrequiring Hip–mPFC interactions, including spatial navigation. Here, we tested the effect of ReRh lesions on the firing properties andspatial activity of dorsal hippocampal CA1 place cells as male rats explored a familiar or a novel environment. We found no change in thespatial characteristics of CA1 place cells in the familiar environment following ReRh lesions. Contrariwise, spatial coherence was decreasedduring the first session in a novel environment. We then investigated field stability of place cells recorded across 5 d both in thefamiliar and in a novel environment presented in a predefined sequence. While the remapping capacity of the place cells was not affectedby the lesion, our results clearly demonstrated a disruption of the CA1 cellular representation of both environments in ReRh rats. Morespecifically, we found ReRh lesions to produce (1) a pronounced and long-lasting decrease of place field stability and (2) a strongalteration of overdispersion (i.e., firing variability). Thus, in ReRh rats, exploration of a novel environment appears to interfere with therepresentation of the familiar one, leading to decreased field stability in both environments. The present study shows the involvement ofReRh nuclei in the long-term spatial stability of CA1 place fields

Using MRI to predict the fate of excitotoxic lesions in rats

International audienceExcitotoxic lesions are frequently used to assess the role of cerebral structures in cognitive processes in rodents. However, the precise site and extent of these lesions remain unknown without histological verifications. Using a 7-Teslas MRI system and a T2-weighted turbo-RARE sequence, MR images were acquired at several time points following NMDA lesions (1h, 6h, 24h, 48h, 1 week and 2 weeks). NMDA infusions into the parenchyma induced a clear and delineable hyperintense signal from 1h up to 1-week post-surgery. Hyperintensity volumes were compared with NeuN and Cresyl violet histological quantifications of the lesion magnitude. NMDA-induced hypersignal is observed as soon as 1h post-injection and is a reliable estimate of the presence (or absence) of a lesion. Compared to NeuN, Cresyl violet staining underestimates the extent of the lesion in significant proportions. The MRI hyperintensity generated by NMDA instillation into the parenchyma can be used as a powerful tool to confirm the diffusion of the drug into the cerebral tissue, to ascertain the locus of injection and predict with a high success rate the fate of NMDA lesions as soon as 1h post-surgery. This approach could be very useful in a large variety of lesion studies in rodents

Using MRI to predict the fate of excitotoxic lesions in rats

International audienceExcitotoxic lesions are frequently used to assess the role of cerebral structures in cognitive processes in rodents. However, the precise site and extent of these lesions remain unknown without histological verifications. Using a 7-Teslas MRI system and a T2-weighted turbo-RARE sequence, MR images were acquired at several time points following NMDA lesions (1h, 6h, 24h, 48h, 1 week and 2 weeks). NMDA infusions into the parenchyma induced a clear and delineable hyperintense signal from 1h up to 1-week post-surgery. Hyperintensity volumes were compared with NeuN and Cresyl violet histological quantifications of the lesion magnitude. NMDA-induced hypersignal is observed as soon as 1h post-injection and is a reliable estimate of the presence (or absence) of a lesion. Compared to NeuN, Cresyl violet staining underestimates the extent of the lesion in significant proportions. The MRI hyperintensity generated by NMDA instillation into the parenchyma can be used as a powerful tool to confirm the diffusion of the drug into the cerebral tissue, to ascertain the locus of injection and predict with a high success rate the fate of NMDA lesions as soon as 1h post-surgery. This approach could be very useful in a large variety of lesion studies in rodents

Using MRI to predict the fate of excitotoxic lesions in rats.

Excitotoxic lesions are frequently used to assess the role of cerebral structures in cognitive processes in rodents. However, the precise site and extent of these lesions remain unknown without histological verifications. Using a 7-Teslas MRI system and a T2-weighted turbo-RARE sequence, MR images were acquired at several time points following NMDA lesions (1h, 6h, 24h, 48h, 1 week and 2 weeks). NMDA infusions into the parenchyma induced a clear and delineable hyperintense signal from 1h up to 1-week post-surgery. Hyperintensity volumes were compared with NeuN and Cresyl violet histological quantifications of the lesion magnitude. NMDA-induced hypersignal is observed as soon as 1h post-injection and is a reliable estimate of the presence (or absence) of a lesion. Compared to NeuN, Cresyl violet staining underestimates the extent of the lesion in significant proportions. The MRI hyperintensity generated by NMDA instillation into the parenchyma can be used as a powerful tool to confirm the diffusion of the drug into the cerebral tissue, to ascertain the locus of injection and predict with a high success rate the fate of NMDA lesions as soon as 1h post-surgery. This approach could be very useful in a large variety of lesion studies in rodents

The reuniens and rhomboid nuclei of the thalamus: A crossroads for cognition-relevant information processing?

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Comparison of the <i>post-mortem</i> estimations of the lesion extent (NeuN / Cresyl violet / MRI).

<p>(A) Comparison of the estimated volumes of the lesion using NeuN and Cresyl violet techniques. *<i>p</i> = 0.015. (B-B’) Typical examples of NeuN immunostained and Cresyl violet stained adjacent brain sections of the same NMDA animal. The dotted lines delineate the extent of the lesion. Note the lower estimation when using Cresyl violet and the clear and easy to draw lesion area when using NeuN. (C) Estimated volumes of the medial habenula nuclei using NeuN immunostaining and Cresyl violet staining. The volume of this structure was evaluated in order to control for an eventual effect of NeuN and Cresyl violet staining on brain tissues (e.g., a different shrinkage effect due to distinct chemical treatments). (D-D’) Typical examples of NeuN immunostained and Cresyl violet stained adjacent brain sections. The dotted lines delineate the left and right medial habenula nuclei. (E) Estimations of the MRI hyperintensity volume observed 1h, 6h, 24h, 48h and 1 week following NMDA instillations targeting the ventral midline thalamus. Estimated lesion volume using NeuN is also indicated as the reference method to evaluate lesion extent. The numbers at the base of the histograms indicate the number of animals considered at each time point. * significantly different from NeuN estimation, <i>p</i> < 0.000001 (1h), p = 0.000145 (6h), p = 0.0011 (24h) and <i>p</i> = 0.000733 (48h). # significantly different from 1h MRI estimation, <i>p</i> = 0.041045 (48h) and <i>p</i> = 0.000843 (1 week). (F) Lesion volume (NeuN) and 1h MRI hyperintensity volume for each successfully-lesioned animal. Note that the volume of the MRI hyperintensity observed at 1h is always significantly greater than the final estimation of the lesion extent using NeuN. (G) Lesion volume (NeuN) and 1h MRI hyperintensity volume for each non-lesioned animal. Note that a small volume of MRI hyperintensity is always associated with no / insufficient lesion volume. Indeed, absent or reduced MRI hyperintensity 1h following NMDA instillations indicates a missed lesion surgery and can be used as a criterion to exclude the animal from further experiments. (H) Lesion volume (NeuN) and MRI hypersignal volume for each NMDA animal subjected to 1 week MRI acquisition. Note that the volume of the MRI hypersignal observed 1 week after NMDA instillation is greater than the final estimation of the lesion extent (NeuN) in 3 animals, lower in 3 animals, and similar in 2 animals.</p

Imaging timeline.

<p>Timeline of MR imaging for each group of rats (lesion, no lesion and sham). “n” indicates the number of animals imaged at each time point (1 hour, 6h, 24h, 48h, 1 week, 2w), while N is the number of animals sacrificed at early (2w) or late (5–6 months) time points.</p