Attenuated Levels of Hippocampal Connexin 43 and its Phosphorylation Correlate with Antidepressant- and Anxiolytic-Like Activities in Mice.

Clinical and preclinical studies have implicated glial anomalies in major depression. Conversely, evidence suggests that the activity of antidepressant drugs is based, at least in part, on their ability to stimulate density and/or activity of astrocytes, a major glial cell population. Despite this recent evidence, little is known about the mechanism(s) by which astrocytes regulate emotionality.

Environmental enrichment does not influence hypersynchronous network activity in the Tg2576 mouse model of Alzheimer's disease.

The cognitive reserve hypothesis claims that the brain can overcome pathology by reinforcing preexistent processes or by developing alternative cognitive strategies. Epidemiological studies have revealed that this reserve can be built throughout life experiences as education or leisure activities. We previously showed that an early transient environmental enrichment (EE) durably improves memory performances in the Tg2576 mouse model of Alzheimer's disease (AD).

Early onset of hypersynchronous network activity and expression of a marker of chronic seizures in the Tg2576 mouse model of Alzheimer's disease.

Cortical and hippocampal hypersynchrony of neuronal networks seems to be an early event in Alzheimer's disease pathogenesis. Many mouse models of the disease also present neuronal network hypersynchrony, as evidenced by higher susceptibility to pharmacologically-induced seizures, electroencephalographic seizures accompanied by spontaneous interictal spikes and expression of markers of chronic seizures such as neuropeptide Y ectopic expression in mossy fibers. This network hypersynchrony is thought to contribute to memory deficits, but whether it precedes the onset of memory deficits or not in mouse models remains unknown.

Environmental enrichment rescues memory in mice deficient for the polysialytransferase ST8SiaIV.

The neural cell adhesion molecule NCAM and its association with the polysialic acid (PSA) are believed to contribute to brain structural plasticity that underlies memory formation. Indeed, the attachment of long chains of PSA to the glycoprotein NCAM down-regulates its adhesive properties by altering cell-cell interactions. In the brain, the biosynthesis of PSA is catalyzed by two polysialyltransferases, which are differentially regulated during lifespan.

Anisomycin injection in area CA3 of the hippocampus impairs both short-term and long-term memories of contextual fear.

Protein synthesis is involved in the consolidation of short-term memory into long-term memory. Previous electrophysiological data concerning LTP in CA3 suggest that protein synthesis in that region might also be necessary for short-term memory. We tested this hypothesis by locally injecting the protein synthesis inhibitor anisomycin in hippocampal area CA1 or CA3 immediately after contextual fear conditioning.

A specific role for hippocampal mossy fiber's zinc in rapid storage of emotional memories.

We investigated the specific role of zinc present in large amounts in the synaptic vesicles of mossy fibers and coreleased with glutamate in the CA3 region. In previous studies, we have shown that blockade of zinc after release has no effect on the consolidation of spatial learning, while zinc is required for the consolidation of contextual fear conditioning. Although both are hippocampo-dependent processes, fear conditioning to the context implies a strong emotional burden.

1H NMR metabolomic signatures in five brain regions of the AβPPswe Tg2576 mouse model of Alzheimer's disease at four ages.

In the quest for biomarkers of onset and progression of Alzheimer's disease, a 1H NMR-based metabolomic study was performed on the simple single-transgenic Tg2576 mouse model. These mice develop a slow cognitive decline starting by 6 months and express amyloid plaques from 10 months of age. The metabolic profiles of extracts from five brain regions (frontal cortex, rhinal cortex, hippocampus, midbrain, and cerebellum) of Tg2576 male mice were compared to those of controls, at 1, 3, 6 and 11 months of age.

Modifications of hippocampal circuits and early disruption of adult neurogenesis in the tg2576 mouse model of Alzheimer's disease.

At advanced stages of Alzheimer's disease, cognitive dysfunction is accompanied by severe alterations of hippocampal circuits that may largely underlie memory impairments. However, it is likely that anatomical remodeling in the hippocampus may start long before any cognitive alteration is detected. Using the well-described Tg2576 mouse model of Alzheimer's disease that develops progressive age-dependent amyloidosis and cognitive deficits, we examined whether specific stages of the disease were associated with the expression of anatomical markers of hippocampal dysfunction.

Differential needs of zinc in the CA3 area of dorsal hippocampus for the consolidation of contextual fear and spatial memories.

One peculiarity of the hippocampal CA3 mossy fiber terminals is the co-release of zinc and glutamate upon synaptic transmission. How these two players act on hippocampal-dependent memories is still unclear. To decipher their respective involvement in memory consolidation, a pharmacological approach was chosen.

Copper chelator induced efficient episodic memory recovery in a non-transgenic Alzheimer's mouse model.

Alzheimer's disease (AD) is a neurodegenerative syndrom involving many different biological parameters, including the accumulation of copper metal ions in Aβ amyloid peptides due to a perturbation of copper circulation and homeostasis within the brain. Copper-containing amyloids activated by endogenous reductants are able to generate an oxidative stress that is involved in the toxicity of abnormal amyloids and contribute to the progressive loss of neurons in AD. Since only few drugs are currently available for the treatment of AD, we decided to design small molecules able to interact with copper and we evaluated these drug-candidates with non-transgenic mice, since AD is mainly an aging disease, not related to genetic disorders.

Transient enriched housing before amyloidosis onset sustains cognitive improvement in Tg2576 mice.

Levels of educational and occupational attainment, as components of cognitive reserve, may modify the relationship between the pathological hallmarks and cognition in Alzheimer's disease (AD). We examined whether exposure of a Tg2576 transgenic mouse model of AD to environmental enrichment (EE) at a specific period during the amyloidogenic process favored the establishment of a cognitive reserve. We found that exposure to EE during early adulthood of Tg2576 mice--before amyloidogenesis has started--reduced the severity of AD-related cognitive deficits more efficiently than exposure later in life, when the pathology is already present.

Central locomotor and cognitive effects of a NPFF receptor agonist in mouse.

NPFF receptors are expressed in several brain regions directly or indirectly involved in cognition and behavior. However, the cognitive effects of the NPFF system have been poorly studied. Therefore, the aim of our study was to analyze the effects of i.

Activation of metabotropic glutamate receptor type 2/3 supports the involvement of the hippocampal mossy fiber pathway on contextual fear memory consolidation.

Elucidating the functional properties of the dentate gyrus (DG), CA3, and CA1 areas is critical for understanding the role of the dorsal hippocampus in contextual fear memory processing. In order to specifically disrupt various hippocampal inputs, we used region-specific infusions of DCG-IV, the metabotropic glutamate receptor agonist, which selectively disrupts entorhinal outputs as well as mossy fiber transmission in the hippocampus. The consequences of these injections were studied using a contextual fear conditioning (CFC) paradigm.

Involvement of hippocampal CA3 K(ATP) channels in contextual memory.

This paper evaluates the involvement of hippocampal ATP-sensitive potassium channels (K(ATP)) in learning and memory. After confirming expression of the Kir6.2 subunit in the CA3 region of C57BL/6J mice, we performed intra-hippocampal pharmacological injections of specific openers and blockers of K(ATP) channels.

Effects of the genetic background on cognitive performances of TG2576 mice.

Animal models of genetic diseases obtained by transferring human mutated genes in the mouse are widely used in biomedical based research. They constitute efficient tools to study mechanisms underlying abnormal phenotypes. Unfortunately, the phenotype of the transgene is often obscured by the genetic background of the embryonic stem cells and that of the recipient strain used to create the transgenic line.

Transient activation of the CA3 Kappa opioid system in the dorsal hippocampus modulates complex memory processing in mice.

The hippocampus plays a central role in various forms of complex learning and memory. Opioid peptides and receptors are abundant in the hippocampus. These peptides are co-released with glutamate from mossy fiber- and lateral perforant path-synapses.

A neuropeptide FF agonist blocks the acquisition of conditioned place preference to morphine in C57Bl/6J mice.

Neuropeptide FF behaves as an opioid-modulating peptide that seems to be involved in morphine tolerance and physical dependence. Nevertheless, the effects of neuropeptide FF agonists on the rewarding properties of morphine remain unknown. C57BL6 mice were conditioned in an unbiased balanced paradigm of conditioned place preference to study the effect of i.

Encoding, consolidation, and retrieval of contextual memory: differential involvement of dorsal CA3 and CA1 hippocampal subregions.

Studies on human and animals shed light on the unique hippocampus contributions to relational memory. However, the particular role of each hippocampal subregion in memory processing is still not clear. Hippocampal computational models and theories have emphasized a unique function in memory for each hippocampal subregion, with the CA3 area acting as an autoassociative memory network and the CA1 area as a critical output structure.

Disruption of hippocampal CA3 network: effects on episodic-like memory processing in C57BL/6J mice.

Lesion studies have demonstrated the prominent role of the hippocampus in spatial and contextual learning. To better understand how contextual information is processed in the CA3 region during learning, we focused on the CA3 autoassociative network hypothesis. We took advantage of a particularity of the mossy fibre (MF) synapses, i.