Facilitation de la mémoire spatiale chez des souris génétiquement modifiées (rôle de récepteur sérotonine 1B et de la phosphatase calcineurine)

BORDEAUX1-BU Sciences-Talence (335222101) / SudocSudocFranceF

The H/Rouen mouse model displays depression-like and anxiety-like behaviors

Cardinal symptoms of depression include helplessness and anhedonia. In addition, depression and anxiety are often comorbid disorders. H/Rouen mice, a genetic mouse model of depression, display helpless behavior in the tail suspension test, whereas non-helpless NH/Rouen mice show the opposite behavior. It is unknown whether H/Rouen mice display an anxious behavior as compared to NH/Rouen mice, and is unclear whether they display anhedonia. Time spent in the periphery of an open-field, an index of anxiety, was found to be higher in male and female H/Rouen mice as compared to NH/Rouen mice. In the elevated plus-maze, a decrease in the number of entries and in the time spent in the open arms was observed in both male and female H/Rouen. In the light/dark box, the number of entries and the time spent in the anxiogenic bright compartment was significantly reduced in male and female H/Rouen mice. In addition, the preference of consumption of a 2% sucrose solution was significantly reduced in male and female H/Rouen mice as compared to NH/Rouen and I/Rouen mice in a two-bottle choice paradigm but was restored by a chronic (3 weeks) fluoxetine treatment. H/Rouen mice thus display both anxiety and anhedonia making them a potent animal model in the treatment of forms depression comorbidly expressed with anxiety

Chronic enhancement of CREB activity in the hippocampus interferes with the retrieval of spatial information

The activation of cAMP-responsive element-binding protein (CREB)-dependent gene expression is thought to be critical for the formation of different types of long-term memory. To explore the consequences of chronic enhancement of CREB function on spatial memory in mammals, we examined spatial navigation in bitransgenic mice that express in a regulated and restricted manner a constitutively active form of CREB, VP16-CREB, in forebrain neurons. We found that chronic enhancement of CREB activity delayed the acquisition of an allocentric strategy to solve the hidden platform task. The ability to turn on and off transgene expression allowed us to dissect the role of CREB in dissociable memory processes. In mice in which transgene expression was turned on during memory acquisition, turning off the transgene re-established the access to the memory trace, whereas in mice in which transgene expression was turned off during acquisition, turning on the transgene impaired memory expression in a reversible manner, indicating that CREB enhancement specifically interfered with the retrieval of spatial information. The defects on spatial navigation in mice with chronic enhancement of CREB function were not corrected by conditions that increased further CREB-dependent activation of hippocampal memory systems, such as housing in an enriched environment. These results along with previous findings in CREB-deficient mutants indicate that the relationship of CREB-mediated plasticity to spatial memory is an inverted-U function, and that optimal learning in the water maze requires accurate regulation of this pathway

Short-term memory and plasticity are impaired in mice lacking melanin concentrating hormone neurons

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Altered Hippocampal Transcript Profile Accompanies an Age-Related Spatial Memory Deficit in Mice

We have carried out a global survey of age-related changes in mRNA levels in the C57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged mice displayed a mild but specific deficit in spatial memory in the Morris water maze. By using Affymetrix GeneChip microarrays, we found a distinct pattern of age-related change, consisting mostly of gene overexpression in the middle-aged mice, suggesting that the induction of negative regulators in the middle-aged hippocampus could be involved in impairment of learning. Interestingly, we report changes in transcript levels for genes that could affect synaptic plasticity. Those changes could be involved in the memory deficits we observed in the 15-month-old mice. In agreement with previous reports, we also found altered expression in genes related to inflammation, protein processing, and oxidative stress

Post-learning paradoxical sleep deprivation impairs reorganization of limbic and cortical networks associated with consolidation of remote contextual fear memory in mice

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Working and Reference Memory tasks trigger opposed long-term synaptic changes in the rat dentate gyrus

International audienceAbstract Long-term storage of information into memory is supposed to rely on long-term synaptic plasticity processes. The detection of such synaptic changes after training in long-term/reference memory (RM) tasks has yet been scarce, variable and only studied on a short time scale. Short-term or working memory (WM) is largely known to depend on persistent neuronal activity or short-term plasticity. However, processing information into WM could also involve long-term synaptic changes that could be responsible for the erasure/forgetting of items previously stored in WM and acting as proactive interference. In order to study long-term synaptic changes associated with RM or WM, we trained chronically implanted rats in 3 different radial maze tasks: a classical RM task and 2 WM tasks involving different levels of proactive interference. Synaptic responses in the dentate gyrus were recorded during 2 × 24 h in freely moving rats after training. We found that consolidation of long-term information leads first to a delayed synaptic potentiation, occurring 9 h after RM training that is replaced by a synaptic depression once the RM rule is fully acquired. In contrast, optimal information processing into WM triggers a synaptic depression immediately after training and lasting 3 h that could act as a mechanism for interference erasure/forgetting

Working and Reference Memory Tasks Trigger Opposed Long-Term Synaptic Changes in the Rat Dentate Gyrus

International audienceLong-term storage of information into memory is supposed to rely on long-term synaptic plasticity processes. The detection of such synaptic changes after training in long-term/reference memory (RM) tasks has yet been scarce, variable and only studied on a short time scale. Short-term or working memory (WM) is largely known to depend on persistent neuronal activity or short-term plasticity. However, processing information into WM could also involve long-term synaptic changes that could be responsible for the erasure/forgetting of items previously stored in WM and acting as proactive interference. In order to study long-term synaptic changes associated with RM or WM, we trained chronically implanted rats in 3 different radial maze tasks: a classical RM task and 2 WM tasks involving different levels of proactive interference. Synaptic responses in the dentate gyrus were recorded during 2 × 24 h in freely moving rats after training. We found that consolidation of long-term information leads first to a delayed synaptic potentiation, occurring 9 h after RM training that is replaced by a synaptic depression once the RM rule is fully acquired. In contrast, optimal information processing into WM triggers a synaptic depression immediately after training and lasting 3 h that could act as a mechanism for interference erasure/forgetting

Chromatin acetylation, memory, and LTP are impaired in CBP+/- mice: a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration

We studied a mouse model of the haploinsufficiency form of Rubinstein-Taybi syndrome (RTS), an inheritable disorder caused by mutations in the gene encoding the CREB binding protein (CBP) and characterized by mental retardation and skeletal abnormalities. In these mice, chromatin acetylation, some forms of long-term memory, and the late phase of hippocampal long-term potentiation (L-LTP) were impaired. We ameliorated the L-LTP deficit in two ways: (1) by enhancing the expression of CREB-dependent genes, and (2) by inhibiting histone deacetyltransferase activity (HDAC), the molecular counterpart of the histone acetylation function of CBP. Inhibition of HDAC also reversed the memory defect observed in fear conditioning. These findings suggest that some of the cognitive and physiological deficits observed on RTS are not simply due to the reduction of CBP during development but may also result from the continued requirement throughout life for both the CREB co-activation and the histone acetylation function of CBP.A.B. is supported by a grant from the Hereditary Disease Foundation. E.R.K is supported by Howard Hughes Medical Institute, by the G. Harold and Leila Y. Mathers Foundation, and by Columbia University Alzheimer's Research Center grant P50 AG08702.Peer reviewe