Low concentrations of aluminum hydroxide adjuvant, forming limited size aggregates, selectively induce cerebral aluminum increase and long-term neurotoxicity in mouse

International audienceBackgroundAluminium hydroxide (alum) has long been added as an adjuvant of vaccines. It consists of nanoparticles forming aggregates. Unexpectedly long-lasting biopersistence of alum aggregates were found within immune cells of patients with chronic fatigue, cognitive dysfunction, myalgias and dysimmunity [1], [2]. We documented in mice slow translocation of alum aggregates captured by monocyte-lineage cells from the injected muscle to brain [3], [4], [5]. Herein, brain function and aluminium (Al) concentration were examined long after injections.MethodsAlhydrogel® was injected in TA muscle in adult female CD1 mice at 3 doses ranging from 133 to 800 μg Al/kg. Eight validated tests were used to evaluate cognitive and motor performances 180 days after injection. Brains were collected for Al level determination and Iba-1 immunohistochemistry.ResultsA most unusual neuro-toxicological pattern limited to lower doses of alum was observed. Neurobehavioral changes, including decreased activity levels and altered anxiety-like behaviour, were documented in animals exposed to the two lowest doses (133 and 200 μg Al/kg) but not at the highest dose (800 μg Al/kg), compared to controls. Consistently, cerebral Al levels were increased in animals exposed to the lowest doses. Microglial cell increase was found in amygdala of the 200 μg Al/kg group. Interestingly, the injected suspensions corresponding to the two lowest doses contained much smaller aggregates (1.50–1.75 μm) compared to the highest dose (4.70 μm).ConclusionAlum particles injected in muscle may induce neurotoxic effects and Al cerebral accumulation six months after injection in mice. Neurotoxic effects are restricted to low concentration suspensions forming small particle aggregates. Such bacteria-sized aggregates are known to be selectively captured by monocyte-lineage cells. This study strongly suggests that, in contrast to “the dose makes the poison” paradigm of classical toxicology, alum toxicology obeys the specific rules of small particle toxicology, thus deserving in depth revaluation. (This study was supported by ANSM)

Indices de fréquentation au Néolithique ancien et occupations du Bronze final au second âge du Fer, au pied du Mont Berru (Berru - Marne, « La Maladerie »): Rapport de fouille archéologique 2014

International audienceLa fouille réalisée sur la commune de Berru (Marne) au lieu-dit « La Maladrerie », se situe au pied du versant nord du mont de Berru, butte témoin du plateau tertiaire d’Île de France. Si le secteur est réputé pour ses découvertes lithiques préhistoriques, il l’est surtout pour ses nécropoles du début du second âge du Fer. Ces anciennes fouilles de la fin du XIXe et du début du XXe siècle ont contribué à définir la chronologie de La Tène ancienne en France septentrionale, ainsi que le groupe social singularisé par les tombes à char. La tombe à char du lieu-dit « le Terrage » est un des exemples les plus anciens du groupe 1 des tombes à chars, attribuée à la fin du Ve et au début du IVe siècle avant notre ère et connue pour avoir livré le casque de « type Berru » : un casque en bronze martelé orné de corail et de palmettes gréco-étrusques gravées, caractéristiques du Premier style de l’art celtique

Assessment of the neurotoxic effects of aluminum hydroxide vaccine adjuvant injections in mice

50th Congress of the European-Societies-of-Toxicology, Edinburgh, SCOTLAND, SEP 07-10, 2014International audienceno abstrac

La séquence loessique Pléistocène moyen à supérieur d'Etricourt-Manancourt (Picardie, France) : un enregistrement pédo-sédimentaire de référence pour les derniers 350 ka

International audienceIn this study, we describe a new Middle Pleistocene loess-palaeosol sequence uncovered during a preventive excavation at Étricourt-Manancourt (Somme, France; fig. 1). The full 12-m-thick sequence exhibits five stacked glacial-interglacial cycles and integrates five in situ Palaeolithic levels and remarkably one Acheulean level dated by TL on burned flints at about 280 - 300 ka.Detailed field stratigraphic approach has been completed by (1) a high-resolution sedimentological study (grain size, TOC) based on a set of more than 380 5-cm-thick samples collected from continuous sampling columns covering the entire units, (2) more than 110 micromorphological block samples for thin sections analysis (fig. 3) and (3) a set of 37 sub-samples for the study of heavy minerals. Despite specific samples (tubes) having been extracted for future OSL dating, the geochronological control is mainly based on TL dating of heated (archaeological) flints, completed by IRSL dating on K-feldspars.The archaeological excavation, located on the slope of a dry valley, was opened over more than 4500 m² and led to the discovery of two deep sinkholes developed in the chalk bedrock (fig. 6). The bottom of the deepest one is located at more than 11 m from the surface of the topsoil and 5 m below the average chalk surface. The study of four reference profiles distributed throughout the excavation (figs. 6-9), and their correlation using well defined pedological level marks led to the definition of a ca. 12-m-thick cumulative loess-palaeosols succession including eighteen main stratigraphic units. This approach allowed building a global pedosedimentary sequences for the Étricourt site that presently serves as a reference for northern France (fig. 14 & tab. 2).Here we focus mainly on the detailed description and analysis of palaeosols. The Étricourt sequence includes five luvisols attributed to full interglacial conditions and allocated to MIS 11 (unit 17), MIS 9 (unit 14), MIS 7 (units 8b and 8a) and MIS 5 (unit 5). Two luvisols are thus identified for MIS 7. The pedosedimentary records corresponding to MIS 9 and MIS 5 are represented by well-developed pedocomplexes corresponding to the superimposition of a truncated luvisol and a humic soil complex that includes systematically a grey forest soil (greyzem).During MIS 9e, a luvisol developed on loessic deposits. The truncation of this Bt horizon (unit 14), and its degradation by hydromorphy and solifluction, indicate a phase of climatic degradation following the interglacial optimum, which could be correlated with sub-stage 9d. The “Lower Humic Soil Complex” begins then with a thick layer of dark clayey silts including scattered flint gravels (unit 13). It is characterised by a strong increase in TOC concentrations, compared to the underlying Bt horizon and by an important biological activity attested by numerous earthworm chambers, partially filled with clayey pellets. Two types of clay coatings are superimposed in this soil unit: 1) light brown to orange clay coatings and 2) brownish red to blackish micro-laminated clay coatings, typical of grey forest soils (greyzems). This soil type today is associated with forest-steppe environments and continental cool climates. The overlying horizon (unit 12), in which the Acheulean level HUD is preserved, is represented by a compacted grey-brownish loam showing a strong banded fabric of cryogenic origin. However, the lithic artefacts are very well preserved and not gelifracted.This Acheulean level has been dated around 288 ± 21 ka using TL on heated flint. The overlying dark-brown horizon (unit 11) is then characterised by a strong biological activity attested by pluricentimetric burrows and a peak in TOC values (0.20 %) indicating a typical humic steppe soil (Ah) horizon, probably of the chernozem type. According to palaeo-pedological data the Étricourt “Lower Humic Soil Complex” thus exhibits a progressive mutation of the environments from continental forest to forested steppe or steppe associated to a progressive climatic degradation directly following an interglacial (Early Glacial phase). According to both the location of the soil complex within the full sequence and TL dating results, this phase is allocated to the transition between MIS 9 and MIS 8.Within the “Lower Humic Soil Complex” occurs an intense frost episode responsible for the banding of unit 12. Since the lithic artefacts from HUD are not gelifracted, this episode of freezing-thawing must have occurred after the burial of the Palaeolithic artefacts. The following sequence of events may thus be proposed (fig. 17): erosion and degradation of the interglacial Bt horizon (unit 14) at the end of MIS 9e and 9d; formation of unit 13 during MIS 9c (HUZ occupation); erosion of unit 13 during MIS 9d; and formation of steppe soils (units 12 to 10b) during MIS 9a, according to the LR04 stack (Lisiecki & Raymo, 2005), or MIS8 according to Railsback et al. (2015); degradation and intense freeze-thaw episode responsible for the cryoturbation of unit 12 and transition to gleys and loess at the transition between MIS 9a and 8.The following glacial period that can be allocated to MIS 8 is recorded by the deposition of a non-calcareous loess (unit 8c). The overlying luvisol (unit 8b) shows mainly layered grainy clay coatings including alternations of limpid orange clays and layers of quartz grains similar to the surrounding sediment. The subsequent erosion (truncation) of this interglacial Bt horizon is underlined by a flint gravel bed (Cx). The overlying horizon (unit 8a) shows many pedorelics, papules and large soil aggregates resulting from the erosion and the reworking of the underlying Bt (unit 8b). A new illuviation phase then takes place in the channels and inter-aggregate spaces indicating the formation of a luvisol on the colluvium produced by the erosion of the underlying Bt. It is proposed that the first luvisol (unit 8b) correlates with the first peak of the curve LR04 corresponding to a temperate phase of MIS 7, 7e at ca. 240 ka, and the second luvisol (unit 8a) with the two near peaks 7c and 7a (fig. 17).The subsequent erosion of the Saalian luvisol soil complex results in the deposition of a new colluvial unit (unit 7b). The overlying greyish horizon (unit 7a), including a Middle Palaeolithic archaeological level, appears in the same stratigraphic position than the humic soil layers described in regional sequences as Mautort or Gentelles, at the transition between MIS 7 and MIS 6. At Étricourt, the Upper Saalian (MIS 6) is represented by clayey loess (unit 6b), and “limons à doublets” (wavy banded fabric, unit 6a), separated by a strong erosion phase indicated by a bed of gelifracted flints. This gravel bed contains reworked lithic industry, among which a flint likely originating from the underlying Middle Palaeolithic level included in the second MIS 7 luvisol has been dated to 222 ± 20 ka. Finally at the top of the Saalian loess unit (MIS 6) occurs a typical luvisol showing a well-marked Bt argillic horizon (unit 5) allocated to the Last Interglacial optimum (MIS 5e). The overlying Upper Humic Soil Complex exhibits the same pedostratigraphic succession than the Weichselian Early Glacial reference sequence of Saint-Sauflieu (grey forest soils with numerous earthworm chambers and several steppe soils).MIS 8 and MIS 6 loess deposits have been dated using the IRSL dating technique applied to both single and multiple aliquots (IRSLSAR and IRSLMAAD, fig. 15). The MIS 6 loess deposit has been dated to 144-180 ka, in good agreement with its chronostratigraphic attribution. By contrast, the MIS 8 loess deposit yielded an apparent MIS 7 IRSL age (215-251 ka). These underestimated IRSL ages together with the large scatter of the IRSLSAR ages, suggest that the MIS 8 loess has been reworked at the beginning of MIS 7.Using litho-pedostratigraphy and the available geochronological data (TL and IRSL dating), some correlations can be proposed between the Étricourt loess-palaeosols sequence and other sequences from NW Europe (figs. 1 & 20). This approach shows that the “Lower Humic Soil Complex”, corresponding to MIS 9 is definitely better expressed at Étricourt than in other sections of northern France and can be proposed as a new reference for this interglacial. In addition, in the section of Saint-Pierre-lès-Elbeuf in Normandy, the micromorphological study also highlights the development of a grey forest soil during MIS 9/8 transition. MIS 9 would also be represented by the Achenheim III pedocomplex in the Rhine Valley, composed of a non-leached reddish brown soil and one or more humic soil horizons. Further east in Europe, no luvisols are to be observed for MIS 7 in Achenheim and Paudorf sections, likely due to more continental climatic conditions as recorded by the development of chernozem-like soils.Finally, the mineralogical study and especially the green amphibole content allows highlighting similarities between the Étricourt sequence and loess deposits from Belgium (fig. 16). These similarities combined with the available results from other loess sequences from northern France suggest that the five green amphibole groups recently defined in Belgium can be extended to the two regions. In this context, one specific contribution of the mineralogical study in Étricourt is to suggest the existence of a hiatus within MIS 6. Beyond the chronostratigraphic interest of the distribution of green amphiboles, it will be necessary in the future to discuss its implications in terms of sources and paleogeography. Indeed, the Étricourt-Manancourt sequence covers the full Saalian complex, a period that is characterised both by major palaeogeographic changes, including the opening of the Strait of Dover and the transition from the Lower to the Middle Palaeolithic.Cet article se focalise essentiellement sur l’approche paléopédologique d’une nouvelle séquence loessique du Pléistocène moyen découverte à l’occasion d’une fouille archéologique préventive à Étricourt-Manancourt (Somme). Cette séquence, d’une douzaine de mètres cumulés, correspond à cinq cycles glaciaire-interglaciaire et intègre cinq niveaux paléolithiques en place. Elle a fait l’objet d’analyses sédimentologiques et micromorphologiques détaillées ainsi que de datations TL sur silex chauffés et IRSL sur feldspaths potassiques. Elle constitue actuellement une nouvelle séquence de référence pédo-sédimentaire pour la France septentrionale pour la fin du Pléistocène moyen (~ 350-140 ka). L’enregistrement comprend cinq luvisols attribués aux SIM 11, 9, 7 et 5e. Deux luvisols sont identifiés pour le SIM 7. Les enregistrements pédo-sédimentaires des SIM 9 et 5 (complexes de sols) sont dilatés et correspondent à la superposition d’un luvisol et d’un pédocomplexe humifère à sol gris forestier (grisol) de contexte Début Glaciaire. Le complexe de sols humifères inférieur attribuable au SIM 9 (« Complexe de sols d’Étricourt ») représente un enregistrement particulièrement détaillé et unique pour le SIM 9 et la transition avec le SIM 8. Un niveau acheuléen situé au-dessus du sol gris forestier du SIM 9 a été daté autour de 288 ± 21 ka par TL sur silex chauffés. Le loess sus-jacent à ce dernier, corrélé au SIM 8, a donné un âge IRSL apparent SIM 7 (215-251 ka) suggérant un remaniement ou une remobilisation du loess au SIM 7. Un niveau paléolithique moyen conservé dans le second luvisol du SIM 7 a été daté à 222 ± 20 ka par TL. Il est surmonté d’un loess primaire allochtone dont les âges IRSL (144-180 ka) confortent son attribution au SIM 6

Non-linear dose-response of aluminium hydroxide adjuvant particles: Selective low dose neurotoxicity

International audienceAluminium (Al) oxyhydroxide (Alhydrogel®), the main adjuvant licensed for human andanimal vaccines, consists of primary nanoparticles that spontaneously agglomerate. Concernsabout its safety emerged following recognition of its unexpectedly long-lasting biopersistencewithin immune cells in some individuals, and reports of chronic fatigue syndrome, cognitivedysfunction, myalgia, dysautonomia and autoimmune/inflammatory features temporallylinked to multiple Al-containing vaccine administrations. Mouse experiments havedocumented its capture and slow transportation by monocyte-lineage cells from the injectedmuscle to lymphoid organs and eventually the brain. The present study aimed at evaluatingmouse brain function and Al concentration 180 days after injection of various doses ofAlhydrogel® (200, 400 and 800 μg Al/kg of body weight) in the tibialis anterior muscle inadult female CD1 mice. Cognitive and motor performances were assessed by 8 validatedtests, microglial activation by Iba-1 immunohistochemistry, and Al level by graphite furnaceatomic absorption spectroscopy.An unusual neuro-toxicological pattern limited to a low dose of Alhydrogel® was observed.Neurobehavioural changes, including decreased activity levels and altered anxiety-likebehaviour, were observed compared to controls in animals exposed to 200 μg Al/kg but not at400 and 800 μg Al/kg. Consistently, microglial number appeared increased in the ventralforebrain of the 200 μg Al/kg group. Cerebral Al levels were selectively increased in animalsexposed to the lowest dose, while muscle granulomas had almost completely disappeared at 6months in these animals.We conclude that Alhydrogel® injected at low dose in mouse muscle may selectively inducelong-term Al cerebral accumulation and neurotoxic effects. To explain this unexpected result,an avenue that could be explored in the future relates to the adjuvant size since the injectedsuspensions corresponding to the lowest dose, but not to the highest doses, exclusivelycontained small agglomerates in the bacteria-size range known to favour capture and,presumably, transportation by monocyte-lineage cells. In any event, the view thatAlhydrogel® neurotoxicity obeys “the dose makes the poison” rule of classical chemicaltoxicity appears overly simplistic

La séquence loessique Pléistocène moyen à supérieur d’Etricourt‑Manancourt (Picardie, France) : un enregistrement pédo‑sédimentaire de référence pour les derniers 350 ka

Cet article se focalise essentiellement sur l’approche paléopédologique d’une nouvelle séquence loessique du Pléistocène moyen découverte à l’occasion d’une fouille archéologique préventive à Étricourt-Manancourt (Somme). Cette séquence, d’une douzaine de mètres cumulés, correspond à cinq cycles glaciaire-interglaciaire et intègre cinq niveaux paléolithiques en place. Elle a fait l’objet d’analyses sédimentologiques et micromorphologiques détaillées ainsi que de datations TL sur silex chauffés et IRSL sur feldspaths potassiques. Elle constitue actuellement une nouvelle séquence de référence pédo-sédimentaire pour la France septentrionale pour la fin du Pléistocène moyen (~ 350-140 ka). L’enregistrement comprend cinq luvisols attribués aux SIM 11, 9, 7 et 5e. Deux luvisols sont identifiés pour le SIM 7. Les enregistrements pédo-sédimentaires des SIM 9 et 5 (complexes de sols) sont dilatés et correspondent à la superposition d’un luvisol et d’un pédocomplexe humifère à sol gris forestier (grisol) de contexte Début Glaciaire. Le complexe de sols humifères inférieur attribuable au SIM 9 (« Complexe de sols d’Étricourt ») représente un enregistrement particulièrement détaillé et unique pour le SIM 9 et la transition avec le SIM 8. Un niveau acheuléen situé au-dessus du sol gris forestier du SIM 9 a été daté autour de 288 ± 21 ka par TL sur silex chauffés. Le loess sus-jacent à ce dernier, corrélé au SIM 8, a donné un âge IRSL apparent SIM 7 (215-251 ka) suggérant un remaniement ou une remobilisation du loess au SIM 7. Un niveau paléolithique moyen conservé dans le second luvisol du SIM 7 a été daté à 222 ± 20 ka par TL. Il est surmonté d’un loess primaire allochtone dont les âges IRSL (144-180 ka) confortent son attribution au SIM 6.In this study, we describe a new Middle Pleistocene loess-palaeosol sequence uncovered during a preventive excavation at Étricourt-Manancourt (Somme, France; fig. 1). The full 12-m-thick sequence exhibits five stacked glacial-interglacial cycles and integrates five in situ Palaeolithic levels and remarkably one Acheulean level dated by TL on burned flints at about 280 - 300 ka. Detailed field stratigraphic approach has been completed by (1) a high-resolution sedimentological study (grain size, TOC) based on a set of more than 380 5-cm-thick samples collected from continuous sampling columns covering the entire units, (2) more than 110 micromorphological block samples for thin sections analysis (fig. 3) and (3) a set of 37 sub-samples for the study of heavy minerals. Despite specific samples (tubes) having been extracted for future OSL dating, the geochronological control is mainly based on TL dating of heated (archaeological) flints, completed by IRSL dating on K-feldspars. The archaeological excavation, located on the slope of a dry valley, was opened over more than 4500 m² and led to the discovery of two deep sinkholes developed in the chalk bedrock (fig. 6). The bottom of the deepest one is located at more than 11 m from the surface of the topsoil and 5 m below the average chalk surface. The study of four reference profiles distributed throughout the excavation (figs. 6-9), and their correlation using well defined pedological level marks led to the definition of a ca. 12-m-thick cumulative loess-palaeosols succession including eighteen main stratigraphic units. This approach allowed building a global pedosedimentary sequences for the Étricourt site that presently serves as a reference for northern France (fig. 14 & tab. 2). Here we focus mainly on the detailed description and analysis of palaeosols. The Étricourt sequence includes five luvisols attributed to full interglacial conditions and allocated to MIS 11 (unit 17), MIS 9 (unit 14), MIS 7 (units 8b and 8a) and MIS 5 (unit 5). Two luvisols are thus identified for MIS 7. The pedosedimentary records corresponding to MIS 9 and MIS 5 are represented by well-developed pedocomplexes corresponding to the superimposition of a truncated luvisol and a humic soil complex that includes systematically a grey forest soil (greyzem). During MIS 9e, a luvisol developed on loessic deposits. The truncation of this Bt horizon (unit 14), and its degradation by hydromorphy and solifluction, indicate a phase of climatic degradation following the interglacial optimum, which could be correlated with sub-stage 9d. The “Lower Humic Soil Complex” begins then with a thick layer of dark clayey silts including scattered flint gravels (unit 13). It is characterised by a strong increase in TOC concentrations, compared to the underlying Bt horizon and by an important biological activity attested by numerous earthworm chambers, partially filled with clayey pellets. Two types of clay coatings are superimposed in this soil unit: 1) light brown to orange clay coatings and 2) brownish red to blackish micro-laminated clay coatings, typical of grey forest soils (greyzems). This soil type today is associated with forest-steppe environments and continental cool climates. The overlying horizon (unit 12), in which the Acheulean level HUD is preserved, is represented by a compacted grey-brownish loam showing a strong banded fabric of cryogenic origin. However, the lithic artefacts are very well preserved and not gelifracted. This Acheulean level has been dated around 288 ± 21 ka using TL on heated flint. The overlying dark-brown horizon (unit 11) is then characterised by a strong biological activity attested by pluricentimetric burrows and a peak in TOC values (0.20 %) indicating a typical humic steppe soil (Ah) horizon, probably of the chernozem type. According to palaeo-pedological data the Étricourt “Lower Humic Soil Complex” thus exhibits a progressive mutation of the environments from continental forest to forested steppe or steppe associated to a progressive climatic degradation directly following an interglacial (Early Glacial phase). According to both the location of the soil complex within the full sequence and TL dating results, this phase is allocated to the transition between MIS 9 and MIS 8. Within the “Lower Humic Soil Complex” occurs an intense frost episode responsible for the banding of unit 12. Since the lithic artefacts from HUD are not gelifracted, this episode of freezing-thawing must have occurred after the burial of the Palaeolithic artefacts. The following sequence of events may thus be proposed (fig. 17): erosion and degradation of the interglacial Bt horizon (unit 14) at the end of MIS 9e and 9d; formation of unit 13 during MIS 9c (HUZ occupation); erosion of unit 13 during MIS 9d; and formation of steppe soils (units 12 to 10b) during MIS 9a, according to the LR04 stack (Lisiecki & Raymo, 2005), or MIS8 according to Railsback et al. (2015); degradation and intense freeze-thaw episode responsible for the cryoturbation of unit 12 and transition to gleys and loess at the transition between MIS 9a and 8. The following glacial period that can be allocated to MIS 8 is recorded by the deposition of a non-calcareous loess (unit 8c). The overlying luvisol (unit 8b) shows mainly layered grainy clay coatings including alternations of limpid orange clays and layers of quartz grains similar to the surrounding sediment. The subsequent erosion (truncation) of this interglacial Bt horizon is underlined by a flint gravel bed (Cx). The overlying horizon (unit 8a) shows many pedorelics, papules and large soil aggregates resulting from the erosion and the reworking of the underlying Bt (unit 8b). A new illuviation phase then takes place in the channels and inter-aggregate spaces indicating the formation of a luvisol on the colluvium produced by the erosion of the underlying Bt. It is proposed that the first luvisol (unit 8b) correlates with the first peak of the curve LR04 corresponding to a temperate phase of MIS 7, 7e at ca. 240 ka, and the second luvisol (unit 8a) with the two near peaks 7c and 7a (fig. 17). The subsequent erosion of the Saalian luvisol soil complex results in the deposition of a new colluvial unit (unit 7b). The overlying greyish horizon (unit 7a), including a Middle Palaeolithic archaeological level, appears in the same stratigraphic position than the humic soil layers described in regional sequences as Mautort or Gentelles, at the transition between MIS 7 and MIS 6. At Étricourt, the Upper Saalian (MIS 6) is represented by clayey loess (unit 6b), and “limons à doublets” (wavy banded fabric, unit 6a), separated by a strong erosion phase indicated by a bed of gelifracted flints. This gravel bed contains reworked lithic industry, among which a flint likely originating from the underlying Middle Palaeolithic level included in the second MIS 7 luvisol has been dated to 222 ± 20 ka. Finally at the top of the Saalian loess unit (MIS 6) occurs a typical luvisol showing a well-marked Bt argillic horizon (unit 5) allocated to the Last Interglacial optimum (MIS 5e). The overlying Upper Humic Soil Complex exhibits the same pedostratigraphic succession than the Weichselian Early Glacial reference sequence of Saint-Sauflieu (grey forest soils with numerous earthworm chambers and several steppe soils). MIS 8 and MIS 6 loess deposits have been dated using the IRSL dating technique applied to both single and multiple aliquots (IRSLSAR and IRSLMAAD, fig. 15). The MIS 6 loess deposit has been dated to 144-180 ka, in good agreement with its chronostratigraphic attribution. By contrast, the MIS 8 loess deposit yielded an apparent MIS 7 IRSL age (215-251 ka). These underestimated IRSL ages together with the large scatter of the IRSLSAR ages, suggest that the MIS 8 loess has been reworked at the beginning of MIS 7. Using litho-pedostratigraphy and the available geochronological data (TL and IRSL dating), some correlations can be proposed between the Étricourt loess-palaeosols sequence and other sequences from NW Europe (figs. 1 & 20). This approach shows that the “Lower Humic Soil Complex”, corresponding to MIS 9 is definitely better expressed at Étricourt than in other sections of northern France and can be proposed as a new reference for this interglacial. In addition, in the section of Saint-Pierre-lès-Elbeuf in Normandy, the micromorphological study also highlights the development of a grey forest soil during MIS 9/8 transition. MIS 9 would also be represented by the Achenheim III pedocomplex in the Rhine Valley, composed of a non-leached reddish brown soil and one or more humic soil horizons. Further east in Europe, no luvisols are to be observed for MIS 7 in Achenheim and Paudorf sections, likely due to more continental climatic conditions as recorded by the development of chernozem-like soils. Finally, the mineralogical study and especially the green amphibole content allows highlighting similarities between the Étricourt sequence and loess deposits from Belgium (fig. 16). These similarities combined with the available results from other loess sequences from northern France suggest that the five green amphibole groups recently defined in Belgium can be extended to the two regions. In this context, one specific contribution of the mineralogical study in Étricourt is to suggest the existence of a hiatus within MIS 6. Beyond the chronostratigraphic interest of the distribution of green amphiboles, it will be necessary in the future to discuss its implications in terms of sources and paleogeography. Indeed, the Étricourt-Manancourt sequence covers the full Saalian complex, a period that is characterised both by major palaeogeographic changes, including the opening of the Strait of Dover and the transition from the Lower to the Middle Palaeolithic

Regulation of the Hippocampal Network by VGLUT3-Positive CCK- GABAergic Basket Cells

International audienceHippocampal interneurons release the inhibitory transmitter GABA to regulate excitation, rhythm generation and synaptic plasticity. A subpopulation of GABAergic basket cells co-expresses the GABA/glycine vesicular transporters (VIAAT) and the atypical type III vesicular glutamate transporter (VGLUT3); therefore, these cells have the ability to signal with both GABA and glutamate. GABAergic transmission by basket cells has been extensively characterized but nothing is known about the functional implications of VGLUT3-dependent glutamate released by these cells. Here, using VGLUT3-null mice we observed that the loss of VGLUT3 results in a metaplastic shift in synaptic plasticity at Shaeffer’s collaterals - CA1 synapses and an altered theta oscillation. These changes were paralleled by the loss of a VGLUT3-dependent inhibition of GABAergic current in CA1 pyramidal layer. Therefore presynaptic type III metabotropic could be activated by glutamate released from VGLUT3-positive interneurons. This putative presynaptic heterologous feedback mechanism inhibits local GABAergic tone regulates the hippocampal neuronal network

Etricourt-Manancourt (Somme, France) : A Reference Loess Sequence and Archaeological Site for the Last 350 ka

International audienceA new Middle Pleistocene loess-palaeosol sequence was uncovered during a preventive excavation at Étricourt-Manancourt (Somme, France). The full 12-m-thick sequence exhibits five stacked glacial-interglacial cycles and integrates five in situ Palaeolithic levels and remarkably one Acheulean level dated by TL on burned flints at about 280 - 300 ka. Detailed field stratigraphic approach has been completed by a high-resolution sedimentological study (grain size, TOC) based on a set of more than 380 5-cm-thick samples collected from continuous sampling columns covering the entire units, more than 110 micromorphological block samples for thin sections analysis and a set of 37 sub-samples for the study of heavy minerals. Despite specific samples (tubes) having been extracted for future OSL dating, the geochronological control is mainly based on TL dating of heated (archaeological) flints, completed by IRSL dating on K-feldspars. The study of four reference profiles distributed throughout the excavation, and their correlation using well defined pedological level marks led to the definition of a ca. 12-m-thick cumulative loess-palaeosols succession including eighteen main stratigraphic units. This approach allowed building a global pedosedimentary sequences for the Étricourt site that presently serves as a reference for northern France, and more broadly the loess belt.The archaeological excavation, located on the slope of a dry valley, was opened over more than 4500 m². Five in situ Palaeolithic occupations have been excavated, dating from 330 to 70 ka. The youngest occupation dates from 70 to 80 ka (Weichselian) and corresponds to a recent phase of the Middle Palaeolithic. The next two layers belong to the Early Middle Palaeolithic, between 190 and 240 ka (Saalian). Finally, the two oldest layers have dates between 330 and 280 ka (Saalian) and belong to the Lower Palaeolithic. We propose to present the archaeological and chronostratigraphic results of the excavation of Etricourt-Manancourt and its input with high resolution data to the knowledge of the Saalian and the Weichselian in Northern France and in North-Western Europe