Role of the cotransporter KCC2 in cortical excitatory synapse development and febrile seizure susceptibility

Le co-transporteur KCC2 spécifique au potassium et chlore a pour rôle principal de réduire la concentration intracellulaire de chlore, entraînant l’hyperpolarisation des courants GABAergic l’autorisant ainsi à devenir inhibiteur dans le cerveau mature. De plus, il est aussi impliqué dans le développement des synapses excitatrices, nommées aussi les épines dendritiques. Le but de notre projet est d’étudier l’effet des modifications concernant l'expression et la fonction de KCC2 dans le cortex du cerveau en développement dans un contexte de convulsions précoces. Les convulsions fébriles affectent environ 5% des enfants, et ce dès la première année de vie. Les enfants atteints de convulsions fébriles prolongées et atypiques sont plus susceptibles à développer l’épilepsie. De plus, la présence d’une malformation cérébrale prédispose au développement de convulsions fébriles atypiques, et d’épilepsie du lobe temporal. Ceci suggère que ces pathologies néonatales peuvent altérer le développement des circuits neuronaux irréversiblement. Cependant, les mécanismes qui sous-tendent ces effets ne sont pas encore compris. Nous avons pour but de comprendre l'impact des altérations de KCC2 sur la survenue des convulsions et dans la formation des épines dendritiques. Nous avons étudié KCC2 dans un modèle animal de convulsions précédemment validé, qui combine une lésion corticale à P1 (premier jour de vie postnatale), suivie d'une convulsion induite par hyperthermie à P10 (nommés rats LHS). À la suite de ces insultes, 86% des rats mâles LHS développent l’épilepsie à l’âge adulte, au même titre que des troubles d’apprentissage. À P20, ces animaux presentent une augmentation de l'expression de KCC2 associée à une hyperpolarisation du potentiel de réversion de GABA. De plus, nous avons observé des réductions dans la taille des épines dendritiques et l'amplitude des courants post-synaptiques excitateurs miniatures, ainsi qu’un déficit de mémoire spatial, et ce avant le développement des convulsions spontanées. Dans le but de rétablir les déficits observés chez les rats LHS, nous avons alors réalisé un knock-down de KCC2 par shARN spécifique par électroporation in utero. Nos résultats ont montré une diminution de la susceptibilité aux convulsions due à la lésion corticale, ainsi qu'une restauration de la taille des épines. Ainsi, l’augmentation de KCC2 à la suite d'une convulsion précoce, augmente la susceptibilité aux convulsions modifiant la morphologie des épines dendritiques, probable facteur contribuant à l’atrophie de l’hippocampe et l’occurrence des déficits cognitifs. Le deuxième objectif a été d'inspecter l’effet de la surexpression précoce de KCC2 dans le développement des épines dendritiques de l’hippocampe. Nous avons ainsi surexprimé KCC2 aussi bien in vitro dans des cultures organotypiques d’hippocampe, qu' in vivo par électroporation in utero. À l'inverse des résultats publiés dans le cortex, nous avons observé une diminution de la densité d’épines dendritiques et une augmentation de la taille des épines. Afin de confirmer la spécificité du rôle de KCC2 face à la région néocorticale étudiée, nous avons surexprimé KCC2 dans le cortex par électroporation in utero. Cette manipulation a eu pour conséquences d’augmenter la densité et la longueur des épines synaptiques de l’arbre dendritique des cellules glutamatergiques. En conséquent, ces résultats ont démontré pour la première fois, que les modifications de l’expression de KCC2 sont spécifiques à la région affectée. Ceci souligne les obstacles auxquels nous faisons face dans le développement de thérapie adéquat pour l’épilepsie ayant pour but de moduler l’expression de KCC2 de façon spécifique.

Mineralogical composition of the upper 300m of Hole 302-M0002A

During the Arctic Coring Expedition (ACEX), a 428-m-thick sequence of Upper Cretaceous to Quaternary sediments was penetrated. The mineralogical composition of the upper 300 m of this sequence is presented here for the first time. Heavy and clay mineral associations indicate a major and consistent shift in provenance, from the Barents-Kara - western Laptev Sea region, characterized by presence of common clinopyroxene, to the eastern Laptev-East Siberian seas in the upper part of the section, characterized by common hornblende (amphibole). Sea ice originating from the latter source region must have survived at least one summer melt cycle in order to reach the ACEX drill site, if considering modern sea ice trajectories and velocities. This shift in mineral assemblages probably represents the onset of a perennial sea ice cover in the Arctic Ocean, which occurred at about 13 Ma, thus suggesting a coeval freeze in the Arctic and Antarctic regions.

Sulfur-isotope analyses of gypsium samples from the Southeast Greenland margin, southern Alaska and Gulf of Alaska (Table 1)

Gypsum grains were identified in Miocene-Pleistocene sediment cores from two deep-water ODP sites, Site 918 off the SE Greenland margin and Site 887 in the Gulf of Alaska, and in Holocene sediment cores from shallow-water localities in Disenchantment Bay and Muir Inlet in southern Alaska. Although initial morphologic and textural observations suggested a complex system in which the gypsum may have had more than one origin, quantitative sulfur isotope analyses of the gypsum provide evidence of its detrital nature. d34S values in gypsum from southern Alaska range between +0.0 and +7.1 per mil. Gypsum has d34S values between -27.1 and -27.5 per mil in the Gulf of Alaska and values between -28.5 and +0.2 per mil off the SE Greenland margin. All of these isotopic signatures are too highly depleted in d34S to have precipitated from seawater, present or past. In addition there is no significant change in d34S values for gypsum crystals with differing physical characteristics (abraded vs. unabraded) from the same stratigraphic horizon, suggesting all the gypsum is detrital regardless of the degree of abrasion. The isotopic and physical evidence, in combination with the onshore geology the environmental setting, and site characteristics of the gypsum-bearing marine localities, lead us to propose that the ultimate source of the gypsum is precipitation from freeze-induced terrestrial sediment or soil brines. Furthermore the combined evidence suggests that the subsequent occurrence of gypsum in glacimarine sediments results from ice-rafting (by icebergs or sea ice) of the frozen regolith and/or, in the proximal glacimarine setting of southern Alaska, very rapid burial via turbidity currents.

Seasonal mean air temperatures and ice phenology characteristics of Great Bear Lake and Great Slave Lake (2002-2009)

Time series of brightness temperatures (T(B)) from the Advanced Microwave Scanning Radiometer-Earth Observing System (AMSR-E) are examined to determine ice phenology variables on the two largest lakes of northern Canada: Great Bear Lake (GBL) and Great Slave Lake (GSL). T(B) measurements from the 18.7, 23.8, 36.5, and 89.0 GHz channels (H- and V- polarization) are compared to assess their potential for detecting freeze-onset/melt-onset and ice-on/ice-off dates on both lakes. The 18.7 GHz (H-pol) channel is found to be the most suitable for estimating these ice dates as well as the duration of the ice cover and ice-free seasons. A new algorithm is proposed using this channel and applied to map all ice phenology variables on GBL and GSL over seven ice seasons (2002-2009). Analysis of the spatio-temporal patterns of each variable at the pixel level reveals that: (1) both freeze-onset and ice-on dates occur on average about one week earlier on GBL than on GSL (Day of Year (DY) 318 and 333 for GBL; DY 328 and 343 for GSL); (2) the freeze-up process or freeze duration (freeze-onset to ice-on) takes a slightly longer amount of time on GBL than on GSL (about 1 week on average); (3) melt-onset and ice-off dates occur on average one week and approximately four weeks later, respectively, on GBL (DY 143 and 183 for GBL; DY 135 and 157 for GSL); (4) the break-up process or melt duration (melt-onset to ice-off) lasts on average about three weeks longer on GBL; and (5) ice cover duration estimated from each individual pixel is on average about three weeks longer on GBL compared to its more southern counterpart, GSL. A comparison of dates for several ice phenology variables derived from other satellite remote sensing products (e.g. NOAA Interactive Multisensor Snow and Ice Mapping System (IMS), QuikSCAT, and Canadian Ice Service Database) show that, despite its relatively coarse spatial resolution, AMSR-E 18.7 GHz provides a viable means for monitoring of ice phenology on large northern lakes.

Palynology from surface sediment samples of the Arctic Ocean

Freshwater chlorophycean algae are characteristic organic-walled microfossils in recent coastal and shelf sediments from the Beaufort, Laptev and Kara seas (Arctic Ocean). The persistent occurrence of the chlorophycean algae Pediastrum spp. and Botryococcus cf. braunii in marine palynomorph assemblages is related to the discharge of freshwater and suspended matter from the large Siberian and North American rivers into the Arctic shelf seas. The distribution patterns of these algae in the marine environments reflect the predominant deposition of riverine sediments and organic matter along the salinity gradient from the outer estuaries and prodeltas to the shelf break. Sedimentary processes overprint the primary distribution of these algae. Resuspension of sediments by waves and bottom currents may transport sediments in the bottom nepheloid layer along the submarine channels to the shelf break. Bottom sediments and microfossils may be incorporated into sea ice during freeze-up in autumn and winter leading to an export from the shelves into the deep sea. The presence of these freshwater algae in sea-ice and bottom sediments in the central Arctic Ocean confirm that transport in sea ice is an important process which leads to a redistribution of shallow water microfossils.

Sedimentology and age on profile Lz1023

A 270 cm long sediment sequence was recovered with a piston corer from east lobe Bonney, Taylor Valley, Antarctica, and characterized according to its sedimentological, mineralogical, and geochemical properties. It is the first record of such length recovered from east lobe Bonney. The sediment core is mainly composed of halite crystals of different sizes, water, and a relatively low and stable proportion of clastic particles. Although the sediment surface was probably disturbed by the coring process and absence or low contents of organic material or carbonates hampers the establishment of a robust chronology by radiocarbon dating, the core probably contains at least several hundred years of information about the history of the lake and the Bonney basin. Variations in halite crystal sizes and amount as well as variations in the composition of clastic material can be related to past lake level changes and evaporation cycles.

Minimum, maximum and mean annual ground temperatures in permafrost around Abisko ANS between 2008-2009

Monitoring of permafrost has been ongoing since 1978 in the Abisko area, northernmost Sweden, when measurements of active layer thickness started. In 1980, boreholes were drilled in three mires in the area to record permafrost temperatures. Recordings were made twice per year, and the last data were obtained in 2002. During the International Polar Year (2007-2008), new boreholes were drilled within the 'Back to the Future' (BTF) and 'Thermal State of Permafrost' (TSP) projects that enabled year-round temperature monitoring. Mean annual ground temperatures (MAGT) in the mires are close to 0°C, ranging from -0.16 to -0.47°C at 5 m depth. Data from the boreholes show increasing ground temperatures in the upper and lower part by 0.4 to 1°C between 1980 and 2002. At one mire, permafrost thickness has decreased from 15 m in 1980 to ca. 9 m in 2009, with an accelerating thawing trend during the last decade.

Spatial distribution and morphometric analysis of thermokarst lakes and other water bodies : Case study from the sporadic permafrost region, Tavvavuoma, Sweden

Projected air and ground temperatures are expected to be higher in Arctic and sub-Arcticlatitudes and with temperatures already close to the limit where permafrost can exist,resistance against degradation is low. With thawing permafrost, the landscape is modifiedwith depression in which thermokarst lakes emerge. In permafrost soils a considerableamount of soil organic carbon is stored, with the potential of altering climate even furtherif expansion and formation of new thermokarst lakes emerge, as decay releasesgreenhouse gases (C02 and CH4) to the atmosphere. Analyzing the spatial distribution andmorphometry over time of thermokarst lakes and other water bodies, is of importance inaccurately predict carbon budget and feedback mechanisms, as well as to assess futurelandscape layout and these features interaction. Different types of high-spatial resolutionaerial and satellite imageries from 1963, 1975, 2003, 2010 and 2015, were used in bothpre- and post-classification change detection analyses. Using object oriented segmentationin eCognition combined with manual adjustments, resulted in digitalized water bodies>28m2 from which direction of change and morphometric values were extracted. Thequantity of thermokarst lakes and other water bodies was in 1963 n=92, with succeedingyears as a trend decreased in numbers, until 2010-2015 when eleven water bodies wereadded in 2015 (n=74 to n=85). In 1963-2003, area of these water bodies decreased with50 651m2 (189 446-138 795m2) and continued to decrease in 2003-2015 ending at 129337m2. Limnicity decreased from 19.9% in 1963 to 14.6% in 2003 (-5.3%). In 2010 and2015 13.7-13.6%. The late increase in water bodies differs from an earlier hypothesis thatsporadic permafrost regions experience decrease in both area and quantity of thermokarstlakes and water bodies. During 1963-2015, land gain has been in dominance of the ratiobetween the two competing processes of expansion and drainage. In 1963-1975, 55/45%,followed by 90/10% in 1975-2003. After major drainage events, land loss increased to62/38% in 2010-2015. Drainage and infilling rates, calculated for 15 shorelines werevaried across both landscape and parts of shorelines, with in average 0.17/0.15/0.14m/yr.Except for 1963-1975 when rate of change in average was in opposite direction (-0.09m/yr.), likely due to evident expansion of a large thermokarst lake. Using a squaregrid, distribution of water bodies was determined, with an indistinct cluster located in NEand central parts. Especially for water bodies <250m2, which is the dominant area classthroughout 1963-2015 ranging from n=39-51. With a heterogeneous composition of bothsmall and large thermokarst lakes, and with both expansion and drainage altering thelandscape in Tavvavuoma, both positive and negative climate feedback mechanisms are inplay - given that sporadic permafrost still exist.

Beluga whale distribution, migration, and behavior in a changing Pacific Arctic

Thesis (Ph.D.)--University of Washington, 2016-06