Global cerebral ischemia in rats leads to amnesia due to selective neuronal death followed by astroglial scar formation in the CA1 layer.

Global Cerebral Ischemia (GCI) occurs following cardiac arrest or neonatal asphyxia and leads to harmful neurological consequences. In most cases, patients who survive cardiac arrest develop severe cognitive and motor impairments. This study focused on learning and memory deficits associated with brain neuroanatomical reorganization that appears after GCI. The four-vessel occlusion (4VO) model was performed to produce a transient GCI. Hippocampal lesions in ischemic rats were visualized using anatomical Magnetic Resonance Imaging (aMRI). Then, the learning and memory abilities of control and ischemic (bilaterally or unilaterally) rats were assessed through the olfactory associated learning task. Finally, a "longitudinal" histological study was carried out to highlight the cellular reorganizations occurring after GCI. We demonstrated that the imaging, behavioral and histological results are closely related. In fact, aMRI revealed the appearance of hyper-intense signals in the dorsal hippocampus at day 3 post-GCI. Consequently, we showed a rise in cell proliferation (Ki 67+ cells) and endogenous neurogenesis especially in the dentate gyrus (DG) at day 3 post-GCI. Then, hyper-intense signals in the dorsal hippocampus were confirmed by strong neuronal losses in the CA1 layer at day 7 post-GCI. These results were linked with severe learning and memory impairments only in bilaterally ischemic rats at day 14 post-GCI. This amnesia was accompanied by huge astroglial and microglial hyperactivity at day 30 post-GCI. Finally, Nestin+ cells and astrocytes gave rise to astroglial scars, which persisted 60days post-GCI. In the light of these results, the 4VO model appears a reliable method to produce amnesia in order to study and develop new therapeutic strategies.

Estradiol-induced neurogenesis in the female accessory olfactory bulb is required for the learning of the male odor.

Odors processed by the main and accessory olfactory bulbs (MOB, AOB) are important for sexual behavior. Interestingly, both structures continue to receive new neurons during adulthood. A role for olfactory neurogenesis in sexual behavior in female mice has recently been shown and gonadal hormones such as estradiol can modulate adult neurogenesis. Therefore, we wanted to determine the role of estradiol in learning the odors of sexual partners and in the adult neurogenesis of female aromatase knockout mice (ArKO), unable to produce estradiol. Female wild-type (WT) and ArKO mice were exposed to male odors during 7 days, and olfactory preferences, cell proliferation, cell survival and functional involvement of newborn neurons were analyzed, using BrdU injections, in combination with a marker of cell activation (Zif268) and neuronal fate (doublecortin, NeuN). Behavioral tasks indicated that both WT and ArKO females were able to discriminate between the odors of two different males, but ArKO mice failed to learn the familiar male odor. Proliferation of newborn cells was reduced in ArKO mice only in the dentate gyrus of the hippocampus. Olfactory exposure decreased cell survival in the AOB in WT females, suggesting a role for estradiol in a structure involved in sexual behavior. Finally, newborn neurons do not seem to be functionally involved in the AOB of ArKO mice compared with WT, when females were exposed to the odor of a familiar male, suggesting that estradiol-induced neurogenesis in the AOB is required for the learning of the male odor in female mice. Aromatase knockout mice (ArKO) presented deficits in olfactory preferences without affecting their olfactory discrimination abilities, and showed no functional involvement of newborn neurons in the accessory olfactory bulb (AOB) in response to the odor of a familiar male. These results suggest that estradiol-induced neurogenesis in the female AOB is required for the learning of the male odor.

Characterization of spatial memory reconsolidation.

Reconsolidation is necessary for the restabilization of reactivated memory traces. However, experimental parameters have been suggested as boundary conditions for this process. Here we investigated the role of a spatial memory trace's age, strength, and update on the reconsolidation process in mice. We first found that protein synthesis is necessary for reconsolidation to occur in the hippocampal CA3 region after reactivation of partially acquired and old memories but not for strongly acquired and recent memories. We also demonstrated that the update of a previously stable memory required, again, a memory reconsolidation in the hippocampal CA3. Finally, we found that the reactivation of a strongly acquired memory requires an activation of the anterior cingulate cortex as soon as 24 h after acquisition. This study demonstrates the importance of the knowledge of the task on the dynamic nature of memory reconsolidation processing.

Interactions with the young down-regulate adult olfactory neurogenesis and enhance the maturation of olfactory neuroblasts in sheep mothers.

New neurons are continuously added in the dentate gyrus (DG) and the olfactory bulb of mammalian brain. While numerous environmental factors controlling survival of newborn neurons have been extensively studied, regulation by social interactions is less documented. We addressed this question by investigating the influence of parturition and interactions with the young on neurogenesis in sheep mothers. Using Bromodeoxyuridine, a marker of cell division, in combination with markers of neuronal maturation, the percentage of neuroblasts and new mature neurons in the olfactory bulb and the DG was compared between groups of parturient ewes which could interact or not with their lamb, and virgins. In addition, a morphological analysis was performed by measuring the dendritic arbor of neuroblasts in both structures. We showed that the postpartum period was associated with a decrease in olfactory and hippocampal adult neurogenesis. In the olfactory bulb, the suppressive effect on neuroblasts was dependent on interactions with the young whereas in the DG the decrease in new mature neurons was associated with parturition. In addition, dendritic length and number of nodes of neuroblasts were significantly enhanced by interactions with the lamb in the olfactory bulb but not in the DG. Because interactions with the young involved learning of the olfactory signature of the lamb, we hypothesize that this learning is associated with a down-regulation in olfactory neurogenesis and an enhancement of olfactory neuroblast maturation. Our assumption is that fewer new neurons decrease cell competition in the olfactory bulb and enhance maturation of those new neurons selected to participate in the learning of the young odor.

Temporal features of adult neurogenesis: differences and similarities across mammalian species.

Production of new neurons continues throughout life in most invertebrates and vertebrates like crustaceans, fishes, reptiles, birds, and mammals including humans. Most studies have been carried out on rodent models and demonstrated that adult neurogenesis is located mainly in two structures, the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ). If adult neurogenesis is well preserved throughout evolution, yet there are however some features which differ between species. The present review proposes to target similarities and differences in the mechanism of mammalian adult neurogenesis by comparing selected species including humans. We will highlight the cellular composition and morphological organization of the SVZ in primates which differs from that of rodents and may be of functional relevance. We will particularly focus on the dynamic of neuronal maturation in rodents, primates, and humans but also in sheep which appears to be an interesting model due to its similarities with the primate brain.