Paradoxical Role of an Egr Transcription Factor Family Member, Egr2/Krox20, in Learning and Memory

It is well established that Egr1/zif268, a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memories. Recently, the Egr3 family member has also been implicated in learning and memory. Because Egr family members encode closely related zinc-finger transcription factors sharing a highly homologous DNA binding domain that recognises the same DNA sequence, they may have related functions in brain. Another Egr family member expressed in brain, Egr2/Krox20 is known to be crucial for normal hindbrain development and has been implicated in several inherited peripheral neuropathies; however, due to Egr2-null mice perinatal lethality, its potential role in cognitive functions in the adult has not been yet explored. Here, we generated Egr2 conditional mutant mice allowing postnatal, forebrain-specific Cre-mediated Egr2 excision and tested homozygous, heterozygous and control littermates on a battery of behavioural tasks to evaluate motor capacity, exploratory behaviour, emotional reactivity and learning and memory performance in spatial and non-spatial tasks. Egr2-deficient mice had no sign of locomotor, exploratory or anxiety disturbances. Surprisingly, they also had no impairment in spatial learning and memory, taste aversion memory or fear memory using a trace conditioning paradigm. On the contrary, Egr2-deficient mice had improved performance in motor learning on a rotarod, and in object recognition memory. These results clearly do not extend the phenotypic consequences resulting from either Egr1 or Egr3 loss-of-function to Egr2. In contrast, they indicate that Egr family members may have different, and in certain circumstances antagonistic functions in the adult brain

Distinct Functions of Egr Gene Family Members in Cognitive Processes

The different gene members of the Egr family of transcriptional regulators have often been considered to have related functions in brain, based on their co-expression in many cell-types and structures, the relatively high homology of the translated proteins and their ability to bind to the same consensus DNA binding sequence. Recent research, however, suggest this might not be the case. In this review, we focus on the current understanding of the functional roles of the different Egr family members in learning and memory. We briefly outline evidence from mutant mice that Egr1 is required specifically for the consolidation of long-term memory, while Egr3 is primarily essential for short-term memory. We also review our own recent findings from newly generated forebrain-specific conditional Egr2 mutant mice, which revealed that Egr2, as opposed to Egr1 and Egr3, is dispensable for several forms of learning and memory and on the contrary can act as an inhibitory constraint for certain cognitive functions. The studies reviewed here highlight the fact that Egr family members may have different, and in certain circumstances antagonistic functions in the adult brain

Inhibition of PI3K-Akt Signaling Blocks Exercise-Mediated Enhancement of Adult Neurogenesis and Synaptic Plasticity in the Dentate Gyrus

Physical exercise has been shown to increase adult neurogenesis in the dentate gyrus and enhances synaptic plasticity. The antiapoptotic kinase, Akt has also been shown to be phosphorylated following voluntary exercise; however, it remains unknown whether the PI3K-Akt signaling pathway is involved in exercise-induced neurogenesis and the associated facilitation of synaptic plasticity in the dentate gyrus.To gain insight into the potential role of this signaling pathway in exercise-induced neurogenesis and LTP in the dentate gyrus rats were infused with the PI3K inhibitor, LY294002 or vehicle control solution (icv) via osmotic minipumps and exercised in a running wheel for 10 days. Newborn cells in the dentate gyrus were date-labelled with BrdU on the last 3 days of exercise. Then, they were either returned to the home cage for 2 weeks to assess exercise-induced LTP and neurogenesis in the dentate gyrus, or were killed on the last day of exercise to assess proliferation and activation of the PI3K-Akt cascade using western blotting.Exercise increases cell proliferation and promotes survival of adult-born neurons in the dentate gyrus. Immediately after exercise, we found that Akt and three downstream targets, BAD, GSK3beta and FOXO1 were activated. LY294002 blocked exercise-induced phosphorylation of Akt and downstream target proteins. This had no effect on exercise-induced cell proliferation, but it abolished most of the beneficial effect of exercise on the survival of newly generated dentate gyrus neurons and prevented exercise-induced increase in dentate gyrus LTP. These results suggest that activation of the PI3 kinase-Akt signaling pathway plays a significant role via an antiapoptotic function in promoting survival of newly formed granule cells generated during exercise and the associated increase in synaptic plasticity in the dentate gyrus

Object-Place Recognition Learning Triggers Rapid Induction of Plasticity-Related Immediate Early Genes and Synaptic Proteins in the Rat Dentate Gyrus

Long-term recognition memory requires protein synthesis, but little is known about the coordinate regulation of specific genes. Here, we examined expression of the plasticity-associated immediate early genes (Arc, Zif268, and Narp) in the dentate gyrus following long-term object-place recognition learning in rats. RT-PCR analysis from dentate gyrus tissue collected shortly after training did not reveal learning-specific changes in Arc mRNA expression. In situ hybridization and immunohistochemistry were therefore used to assess possible sparse effects on gene expression. Learning about objects increased the density of granule cells expressing Arc, and to a lesser extent Narp, specifically in the dorsal blade of the dentate gyrus, while Zif268 expression was elevated across both blades. Thus, object-place recognition triggers rapid, blade-specific upregulation of plasticity-associated immediate early genes. Furthermore, Western blot analysis of dentate gyrus homogenates demonstrated concomitant upregulation of three postsynaptic density proteins (Arc, PSD-95, and α-CaMKII) with key roles in long-term synaptic plasticity and long-term memory

Metabarcoding as a tool to enhance marine surveillance of nonindigenous species in tropical harbors: A case study in Tahiti

Globalization has increased connectivity between countries enhancing the spread of marine nonindigenous species (NIS). The establishment of marine NIS shows substantial negative effects on the structure and functioning of the natural ecosystems by competing for habitats and resources. Ports are often hubs for the spread of NIS via commercial and recreational vessels. Prevention, detection, and mitigation efforts are required to avoid and manage the establishment of NIS in new ecosystems. In this study, metabarcoding approaches targeting the nuclear small-subunit ribosomal RNA (18S rRNA) gene and mitochondrial cytochrome c oxidase I (COI) gene were used to investigate planktonic and sessile (i.e., biofouling) communities and NIS at four locations in Tahiti, including two marinas and one port with varying anthropogenic impacts, and a relatively pristine site (Manava) used as a control. ASV richness values showed significant differences (18S rRNA gene: p = .023; COI: p < .001) between locations in the plankton samples, with the control site (low impact) having the highest diversity for both genes. ASV richness was also significantly different among locations for the biofouling samples in the COI dataset (p = .002). Community composition differed between locations with spatial patterns appearing stronger for the plankton samples compared with the biofouling samples. Detection of NIS based on selected lists of globally invasive species revealed a wide diversity of potentially invasive taxa especially in the more anthropogenically impacted regions. The use of a multigene approach improved the detection of NIS. This study demonstrates the utility of using a metabarcoding approach to routinely monitor areas most at risk from NIS establishment in Tahiti and other coastal nations. These coastal nations are vulnerable to shipping-mediated incursions, and baseline information is required for both native diversity and nonindigenous diversity.publishedVersio

Production et diffusion de parures néolithiques en séricite et autres micas en quart nord-ouest de la France dans son contexte européen

International audienceAdornments made from sericite and other micas are found mainly in funerary contexts across the northwestern quadrant of France. The analysis of such contexts shows that these objects were used over a long time, as they appear in individual burials dated back to the end of the early Neolithic period, but especially in those contexts belonging to the middle Neolithic 2 period, where they are found in passage graves and even in the tombs with vestibules of the late Neolithic period. Even when the spatial clustering, as well as the identification of roughouts and the presence of vein deposits of this raw material, suggests that the production of sericite adornments was well circumscribed to the Loire-Atlantique, their distribution reaches a radius of 300 km. Furthermore, these ornaments are a very fine example of a good substitute for those objects made from Iberian variscite and turquoise. However, these adornments are not confined to northern France, as evidenced by our first inventory; thus, this type of mineralisation was also used by other western European communities (Switzerland, northern Italy, southern France, Spain and Portugal) as a raw material for making ornaments, the communities among which, we now try to discuss the possible interactions.Les parures en séricite et autres micas se rencontrent principalement au sein des assemblages funéraires sur l’ensemble du quart nord-ouest de la France. L’étude des contextes montre leur emploi à travers une chronologie longue, marquant les sociétés de la fin du Néolithique ancien dans les sépultures individuelles, mais surtout celles du Néolithique moyen 2 où on les retrouve dans les tombes à couloir, jusqu’au Néolithique récent et final dans les tombes à vestibules. Alors que la production de ces parures semble bien circonscrite en Loire-Atlantique, grâce notamment à la reconnaissance spatiale de concentrations de mobilier mais aussi d’ébauches et la présence de gîtes filoniens, leur diffusion porte sur un rayon de 300 km. Ces parures constituent, de plus, un très bon exemple de produit de substitution à celles en variscite et turquoise d’origine ibérique. Mais ces parures en mica ne concernent pas seulement le nord de la France. Comme le montre notre premier inventaire, on rencontre également ce type de minéralisation parmi les parures des communautés d’Europe occidentale (Suisse, Italie du Nord, Midi de la France, Espagne et Portugal), dont nous tâchons d’évoquer les éventuelles interactions

Comparison of Marine Spatial Planning Methods in Madagascar Demonstrates Value of Alternative Approaches

The Government of Madagascar plans to increase marine protected area coverage by over one million hectares. To assist this process, we compare four methods for marine spatial planning of Madagascar's west coast. Input data for each method was drawn from the same variables: fishing pressure, exposure to climate change, and biodiversity (habitats, species distributions, biological richness, and biodiversity value). The first method compares visual color classifications of primary variables, the second uses binary combinations of these variables to produce a categorical classification of management actions, the third is a target-based optimization using Marxan, and the fourth is conservation ranking with Zonation. We present results from each method, and compare the latter three approaches for spatial coverage, biodiversity representation, fishing cost and persistence probability. All results included large areas in the north, central, and southern parts of western Madagascar. Achieving 30% representation targets with Marxan required twice the fish catch loss than the categorical method. The categorical classification and Zonation do not consider targets for conservation features. However, when we reduced Marxan targets to 16.3%, matching the representation level of the “strict protection” class of the categorical result, the methods show similar catch losses. The management category portfolio has complete coverage, and presents several management recommendations including strict protection. Zonation produces rapid conservation rankings across large, diverse datasets. Marxan is useful for identifying strict protected areas that meet representation targets, and minimize exposure probabilities for conservation features at low economic cost. We show that methods based on Zonation and a simple combination of variables can produce results comparable to Marxan for species representation and catch losses, demonstrating the value of comparing alternative approaches during initial stages of the planning process. Choosing an appropriate approach ultimately depends on scientific and political factors including representation targets, likelihood of adoption, and persistence goals

Mécanismes cellulaires et moléculaires de la mémoire

On admet généralement que l’information en mémoire est encodée sous forme de configurations spatio-temporelles d’activité dans des réseaux de neurones distribués et que le stockage de ces représentations repose sur des modifications acquises de la force synaptique au sein des réseaux activés par l’apprentissage. De nombreuses études montrent qu’un des mécanismes de l’apprentissage et de la mémoire au niveau cellulaire repose sur une forme particulièrement durable de plasticité, connue sous le nom de potentialisation à long terme. Les étapes-clés de ces mécanismes de plasticité commencent à être identifiées. Ils nécessitent l’activation de récepteurs spécifiques et un ensemble de cascades d’activations moléculaires permettant la conversion des signaux extracellulaires en changements fonctionnels de la connectivité neuronale. On découvre aussi que la régulation rapide de l’expression de nombreux gènes permet le remodelage durable des réseaux neuronaux à la base de la formation de traces mnésiques stables. Les avancées récentes dans la recherche des mécanismes cellulaires et moléculaires de la mémoire sont résumées

Mécanismes cellulaires et moléculaires de la mémoire

Il est maintenant largement démontré qu’une des caractéristiques fondamentales du cerveau est sa capacité d’exprimer des propriétés de modifiabilité fonctionnelle et structurale par des mécanismes de plasticité qui se trouvent au cœur de nos capacités d’apprentissage et de mémoire. On admet généralement qu’un mécanisme central de la formation des souvenirs repose sur des modifications acquises de la force synaptique et le remodelage des réseaux de neurones activés par l’apprentissage. De nombreuses études montrent qu’un des mécanismes de l’apprentissage et de la mémoire au niveau cellulaire repose sur une forme particulièrement durable de plasticité, connue sous le nom de potentialisation à long terme. Les étapes-clés de ces mécanismes de plasticité commencent à être identifiées. Elles nécessitent l’activation de récepteurs spécifiques et un ensemble de cascades d’activations moléculaires permettant la conversion des signaux extracellulaires en changements fonctionnels de la connectivité neuronale. On découvre aussi que la régulation rapide de programmes d’expression de nombreux gènes dans les neurones permet le remodelage durable des réseaux neuronaux à la base de la formation de traces mnésiques stables. Les avancées récentes dans la recherche des mécanismes cellulaires et moléculaires de la mémoire sont résumées