Reversal of activity-mediated spine dynamics and learning impairment in a mouse model of Fragile X syndrome.

Fragile X syndrome (FXS) is characterized by intellectual disability and autistic traits, and results from the silencing of the FMR1 gene coding for a protein implicated in the regulation of protein synthesis at synapses. The lack of functional Fragile X mental retardation protein has been proposed to result in an excessive signaling of synaptic metabotropic glutamate receptors, leading to alterations of synapse maturation and plasticity. It remains, however, unclear how mechanisms of activity-dependent spine dynamics are affected in Fmr knockout (Fmr1-KO) mice and whether they can be reversed. Here we used a repetitive imaging approach in hippocampal slice cultures to investigate properties of structural plasticity and their modulation by signaling pathways. We found that basal spine turnover was significantly reduced in Fmr1-KO mice, but markedly enhanced by activity. Additionally, activity-mediated spine stabilization was lost in Fmr1-KO mice. Application of the metabotropic glutamate receptor antagonist α-Methyl-4-carboxyphenylglycine (MCPG) enhanced basal turnover, improved spine stability, but failed to reinstate activity-mediated spine stabilization. In contrast, enhancing phosphoinositide-3 kinase (PI3K) signaling, a pathway implicated in various aspects of synaptic plasticity, reversed both basal turnover and activity-mediated spine stabilization. It also restored defective long-term potentiation mechanisms in slices and improved reversal learning in Fmr1-KO mice. These results suggest that modulation of PI3K signaling could contribute to improve the cognitive deficits associated with FXS.

Climate and vegetation history of western Portugal inferred from Albian near-shore deposits (Gale Formation, Lusitanian Basin)

The late Early Cretaceous greenhouse climate has been studied intensively based on proxy data derived essentially from open marine archives. In contrast, information on continental climatic conditions and on the accompanying response of vegetation is relatively scarce, most notably owing to the stratigraphic uncertainties associated with many Lower Cretaceous terrestrial deposits. Here, we present a palynological record from Albian near-shore deposits of the Lusitanian Basin of W Portugal, which have been independently dated using Sr-isotope signals derived from low-Mg oyster shell calcite. Sr-87/Sr-86 values fluctuate between 0.707373 +/- 0.00002 and 0.707456 +/- 0.00003; absolute values and the overall stratigraphic trend match well with the global open marine seawater signature during Albian times. Based on the new Sr-isotope data, existing biostratigraphic assignments of the succession are corroborated and partly revised. Spore-pollen data provide information on the vegetation community structure and are flanked by sedimentological and clay mineralogical data used to infer the overall climatic conditions prevailing on the adjacent continent. Variations in the distribution of climate-sensitive pollen and spores indicate distinct changes in moisture availability across the studied succession with a pronounced increase in hygrophilous spores in late Early Albian times. Comparison with time-equivalent palynofloras from the Algarve Basin of southern Portugal shows pronounced differences in the xerophyte/hygrophyte ratio, interpreted to reflect the effect of a broad arid climate belt covering southern and southeastern Iberia during Early Albian times.

Ecology and life history affect different aspects of the population structure of 27 high-alpine plants.

A plant species' genetic population structure is the result of a complex combination of its life history, ecological preferences, position in the ecosystem and historical factors. As a result, many different statistical methods exist that measure different aspects of species' genetic structure. However, little is known about how these methods are interrelated and how they are related to a species' ecology and life history. In this study, we used the IntraBioDiv amplified fragment length polymorphisms data set from 27 high-alpine species to calculate eight genetic summary statistics that we jointly correlate to a set of six ecological and life-history traits. We found that there is a large amount of redundancy among the calculated summary statistics and that there is a significant association with the matrix of species traits. In a multivariate analysis, two main aspects of population structure were visible among the 27 species. The first aspect is related to the species' dispersal capacities and the second is most likely related to the species' postglacial recolonization of the Alps. Furthermore, we found that some summary statistics, most importantly Mantel's r and Jost's D, show different behaviour than expected based on theory. We therefore advise caution in drawing too strong conclusions from these statistics.

Evolutionary and dispersal history of Eurasian house mice Mus musculus clarified by more extensive geographic sampling of mitochondrial DNA.

We examined the sequence variation of mitochondrial DNA control region and cytochrome b gene of the house mouse (Mus musculus sensu lato) drawn from ca. 200 localities, with 286 new samples drawn primarily from previously unsampled portions of their Eurasian distribution and with the objective of further clarifying evolutionary episodes of this species before and after the onset of human-mediated long-distance dispersals. Phylogenetic analysis of the expanded data detected five equally distinct clades, with geographic ranges of northern Eurasia (musculus, MUS), India and Southeast Asia (castaneus, CAS), Nepal (unspecified, NEP), western Europe (domesticus, DOM) and Yemen (gentilulus). Our results confirm previous suggestions of Southwestern Asia as the likely place of origin of M. musculus and the region of Iran, Afghanistan, Pakistan, and northern India, specifically as the ancestral homeland of CAS. The divergence of the subspecies lineages and of internal sublineage differentiation within CAS were estimated to be 0.37-0.47 and 0.14-0.23 million years ago (mya), respectively, assuming a split of M. musculus and Mus spretus at 1.7 mya. Of the four CAS sublineages detected, only one extends to eastern parts of India, Southeast Asia, Indonesia, Philippines, South China, Northeast China, Primorye, Sakhalin and Japan, implying a dramatic range expansion of CAS out of its homeland during an evolutionary short time, perhaps associated with the spread of agricultural practices. Multiple and non-coincident eastward dispersal events of MUS sublineages to distant geographic areas, such as northern China, Russia and Korea, are inferred, with the possibility of several different routes.

Local adaptation and life history traits evolution in heterogeneous environment : an empirical example in the freshwater snail, Galba truncatula

Abstract: To understand the processes of evolution, biologists are interested in the ability of a population to respond to natural or artificial selection. The amount of genetic variation is often viewed as the main factor allowing a species to answer to selection. Many theories have thus focused on the maintenance of genetic variability. Ecologists and population geneticists have long-suspected that the structure of the environment is connected to the maintenance of diversity. Theorists have shown that diversity can be permanently and stably maintained in temporal and spatial varying environment in certain conditions. Moreover, varying environments have been also theoretically demonstrated to cause the evolution of divergent life history strategies in the different niches constituting the environment. Although there is a huge number of theoretical studies selection and on life history evolution in heterogeneous environments, there is a clear lack of empirical studies. The purpose of this thesis was to. empirically study the evolutionary consequences of a heterogeneous environment in a freshwater snail Galba truncatula. Indeed, G. truncatula lives in two habitat types according the water availability. First, it can be found in streams or ponds which never completely dry out: a permanent habitat. Second, G. truncatula can be found in pools that freeze during winter and dry during summer: a temporary habitat. Using a common garden approach, we empirically demonstrated local adaptation of G. truncatula to temporary and permanent habitats. We used at first a comparison of molecular (FST) vs. quantitative (QST) genetic differentiation between temporary and permanent habitats. To confirm the pattern QST> FST between habitats suggesting local adaptation, we then tested the desiccation resistance of individuals from temporary and permanent habitats. This study confirmed that drought resistance seemed to be the main factor selected between habitats, and life history traits linked to the desiccation resistance were thus found divergent between habitats. However, despite this evidence of selection acting on mean values of traits between habitats, drift was suggested to be the main factor responsible of variation in variances-covariances between populations. At last, we found life history traits variation of individuals in a heterogeneous environment varying in parasite prevalence. This thesis empirically demonstrated the importance of heterogeneous environments in local adaptation and life history evolution and suggested that more experimental studies are needed to investigate this topic. Résumé: Les biologistes se sont depuis toujours intéressés en l'aptitude d'une population à répondre à la sélection naturelle. Cette réponse dépend de la quantité de variabilité génétique présente dans cette population. Plus particulièrement, les théoriciens se sont penchés sur la question du maintient de la variabilité génétique au sein d'environnements hétérogènes. Ils ont alors démontré que, sous certaines conditions, la diversité génétique peut se maintenir de manière stable et permanente dans des environnements variant au niveau spatial et temporel. De plus, ces environments variables ont été démontrés comme responsable de divergence de traits d'histoire de vie au sein des différentes niches constituant l'environnement. Cependant, malgré ce nombre important d'études théoriques portant sur la sélection et l'évolution des traits d'histoire de vie en environnement hétérogène, les études empiriques sont plus rares. Le but de cette thèse était donc d'étudier les conséquences évolutives d'un environnement hétérogène chez un esgarcot d'eau douce Galba truncatula. En effet, G. truncatula est trouvé dans deux types d'habitats qui diffèrent par leur niveau d'eau. Le premier, l'habitat temporaire, est constitué de flaques d'eau qui peuvent s'assécher pendant l'été et geler pendant l'hiver. Le second, l'habitat permanent, correspond à des marres ou à des ruisseaux qui ont un niveau d'eau constant durant toute l'année. Utilisant une approche expérimentale de type "jardin commun", nous avons démontré l'adaptation locale des individus à leur type d'habitat, permanent ou temporaire. Nous avons utilisé l'approche Fsr/QsT qui compare la différentiation génétique moléculaire avec la différentiation génétique quantitative entre les 2 habitats. Le phénomène d'adapation locale démontré par QsT > FsT, a été testé experimentalement en mesurant la résistance à la dessiccation d'individus d'habitat temporaire et permanent. Cette étude confirma que la résistance à la sécheresse a été sélectionné entre habitats et que les traits responsables de cette resistance sont différents entre habitats. Cependant si la sélection agit sur la valeur moyenne des traits entre habitats, la dérive génétique semble être le responsable majeur de la différence de variances-covariances entre populations. Pour finir, une variation de traits d'histoire de vie a été trouvée au sein d'un environnement hétérogène constitué de populations variants au niveau de leur taux de parasitisme. Pour conclure, cette thèse a donc démontré l'importance d'un environnement hétérogène sur l'adaptation locale et l'évolution des traits d'histoire de vie et suggère que plus d'études empiriques sur le sujet sont nécessaires.