Cognitive impairments in a Down syndrome model with abnormal hippocampal and prefrontal dynamics and cytoarchitecture

The Dp(10)2Yey mouse carries a ∼2.3-Mb intra-chromosomal duplication of mouse chromosome 10 (Mmu10) that has homology to human chromosome 21, making it an essential model for aspects of Down syndrome (DS, trisomy 21). In this study, we investigated neuronal dysfunction in the Dp(10)2Yey mouse and report spatial memory impairment and anxiety-like behavior alongside altered neural activity in the medial prefrontal cortex (mPFC) and hippocampus (HPC). Specifically, Dp(10)2Yey mice showed impaired spatial alternation associated with increased sharp-wave ripple activity in mPFC during a period of memory consolidation, and reduced mobility in a novel environment accompanied by reduced theta-gamma phase-amplitude coupling in HPC. Finally, we found alterations in the number of interneuron subtypes in mPFC and HPC that may contribute to the observed phenotypes and highlight potential approaches to ameliorate the effects of human trisomy 21

Neogene calcareous nannofossils in DSDP Site 93-603

Calcareous nannofossils are sufficiently numerous in the upper 900 m of the Neogene sediment drift cored beneath the lower continental rise at DSDP Site 603 to permit delineation of zones, correlations with the paleomagnetic data (Pliocene-Pleistocene only), and the detection of major Miocene hiatuses and their correlation with seismic stratigraphy. Holes 603, 603B, and 6O3C were spudded in lower Pleistocene sediments just east of the crest of the Hatteras Outer Ridge, and all nannofossil zones and subzones are accounted for down to a hiatus within the middle Tortonian (late Miocene) Zone CN8. This hiatus lies some 30 m above a more extensive disconformity between 661 and 672 m where sediments of Subzone CN7a and a portion of Zone CN6 have been removed. The resulting hiatus is correlated with local reflection Horizon M2, which is considered equivalent to the regional Reflector Merlin. The hiatus between 661 and 672 m dates Merlin at this site between about 9.6 and 10.4 Ma. A strong, parallel, unnamed reflector is correlated with the superjacent hiatus within CN8, and is dated between 8.5 and 9 Ma. These disconformities help delineate a "condensed" interval, which falls within the Vail et al. (1980) cycle TM3.1. This eustatic event has been characterized as the sharpest and most profound sea-level drop of the late Miocene. The lower Tortonian "condensed" interval at Site 603 is closely correlative with spectacular debris flows cored in presumed canyon fill deposits immediately above reflection Horizon M2/Merlin at DSDP Site 604 on the upper rise off New Jersey. We suggest that the erosion along the lower rise at Site 603 and the synchronous canyon cutting evidenced by the debris flows on the upper rise at Site 604, both associated with the regional Reflector Merlin, are linked closely to Southern Hemisphere glacial activity which led to the formation of the West Antarctic Ice Sheet. Apart from the lower Tortonian "condensed" interval, the drift sediments of the Hatteras Outer Ridge are primarily muddy contourites, augmented to some extent by fine turbidites in the lower portion. Most were deposited at a rate of about 87 m/Ma. Just after the late Miocene erosional events, sedimentation rates during nannofossil Zone CN8b time were 192 m/Ma, about double that for the overlying section. This suggests that the site was then the locus of deposition for material eroded during canyon-cutting events along the slope and shelf. The lowest sample dated (911 m) is assigned to Subzone CN5b (not older than 13.1 Ma). A rare glauconitic silty sand turbidite at 834.8 m contains upper Eocene coccoliths, probably eroded from submarine outcrops along the slope, perhaps during a brief middle Miocene canyon-cutting episode

Affordable optical clearing and immunolabelling in mouse brain slices

Abstract Traditional histological analysis is conducted on thin tissue sections, limiting the data capture from large tissue volumes to 2D profiles, and requiring stereological methods for 3D assessment. Recent advances in microscopical and tissue clearing methods have facilitated 3D reconstructions of tissue structure. However, staining of large tissue blocks remains a challenge, often requiring specialised and expensive equipment to clear and immunolabel tissue. Here, we present the Affordable Brain Slice Optical Clearing (ABSOC) method: a modified iDISCO protocol which enables clearing and immunolabeling of mouse brain slices up to 1 mm thick using inexpensive reagents and equipment, with no intensive expert training required. We illustrate the use of ABSOC in 1 mm C57BL/6J mouse coronal brain slices sectioned through the dorsal hippocampus and immunolabelled with an anti-calretinin antibody. The ABSOC method can be readily used for histological studies of mouse brain in order to move from the use of very thin tissue sections to large volumes of tissue – giving more representative analysis of biological samples, without the need for sampling of small regions only

Chronic Hippocampal Abnormalities and Blunted HPA Axis in an Animal Model of Repeated Unpredictable Stress

Incidence of post-traumatic stress disorder (PTSD) ranges from 3 to 30% in individuals exposed to traumatic events, with the highest prevalence in groups exposed to combat, torture, or rape. To date, only a few FDA approved drugs are available to treat PTSD, which only offer symptomatic relief and variable efficacy. There is, therefore, an urgent need to explore new concepts regarding the biological responses causing PTSD. Animal models are an appropriate platform for conducting such studies. Herein, we examined the chronic behavioral and neurobiological effects of repeated unpredictable stress (RUS) in a mouse model. 12 weeks-old C57BL/6J male mice were exposed to a 21-day RUS paradigm consisting of exposures to a predator odor (TMT) whilst under restraint, unstable social housing, inescapable footshocks and social isolation. Validity of the model was assessed by comprehensive examination of behavioral outcomes at an acute timepoint, 3 and 6 months post-RUS; and molecular profiling was also conducted on brain and plasma samples at the acute and 6 months timepoints. Stressed mice demonstrated recall of traumatic memories, passive stress coping behavior, acute anxiety, and weight gain deficits when compared to control mice. Immunoblotting of amygdala lysates showed a dysregulation in the p75NTR/ProBDNF, and glutamatergic signaling in stressed mice at the acute timepoint. At 6 months after RUS, stressed mice had lower plasma corticosterone, reduced hippocampal CA1 volume and reduced brain-derived neurotrophic factor levels. In addition, glucocorticoid regulatory protein FKBP5 was downregulated in the hypothalamus of stressed mice at the same timepoint, together implicating an impaired hypothalamus-pituitary-adrenal-axis. Our model demonstrates chronic behavioral and neurobiological outcomes consistent with those reported in human PTSD cases and thus presents a platform through which to understand the neurobiology of stress and explore new therapeutic interventions

Data_Sheet_1_Chronic Hippocampal Abnormalities and Blunted HPA Axis in an Animal Model of Repeated Unpredictable Stress.DOCX

<p>Incidence of post-traumatic stress disorder (PTSD) ranges from 3 to 30% in individuals exposed to traumatic events, with the highest prevalence in groups exposed to combat, torture, or rape. To date, only a few FDA approved drugs are available to treat PTSD, which only offer symptomatic relief and variable efficacy. There is, therefore, an urgent need to explore new concepts regarding the biological responses causing PTSD. Animal models are an appropriate platform for conducting such studies. Herein, we examined the chronic behavioral and neurobiological effects of repeated unpredictable stress (RUS) in a mouse model. 12 weeks-old C57BL/6J male mice were exposed to a 21-day RUS paradigm consisting of exposures to a predator odor (TMT) whilst under restraint, unstable social housing, inescapable footshocks and social isolation. Validity of the model was assessed by comprehensive examination of behavioral outcomes at an acute timepoint, 3 and 6 months post-RUS; and molecular profiling was also conducted on brain and plasma samples at the acute and 6 months timepoints. Stressed mice demonstrated recall of traumatic memories, passive stress coping behavior, acute anxiety, and weight gain deficits when compared to control mice. Immunoblotting of amygdala lysates showed a dysregulation in the p75NTR/ProBDNF, and glutamatergic signaling in stressed mice at the acute timepoint. At 6 months after RUS, stressed mice had lower plasma corticosterone, reduced hippocampal CA1 volume and reduced brain-derived neurotrophic factor levels. In addition, glucocorticoid regulatory protein FKBP5 was downregulated in the hypothalamus of stressed mice at the same timepoint, together implicating an impaired hypothalamus-pituitary-adrenal-axis. Our model demonstrates chronic behavioral and neurobiological outcomes consistent with those reported in human PTSD cases and thus presents a platform through which to understand the neurobiology of stress and explore new therapeutic interventions.</p

Overview of the large-scale biosphere–atmosphere experiment in Amazonia data model intercomparison project (LBA-DMIP)

A fundamental question connecting terrestrial ecology and global climate change is the sensitivity of key terrestrial biomes to climatic variability and change. The Amazon region is such a key biome: it contains unparalleled biological diversity, a globally significant store of organic carbon, and it is a potent engine driving global cycles of water and energy. The importance of understanding how land surface dynamics of the Amazon region respond to climatic variability and change is widely appreciated, but despite significant recent advances, large gaps in our understanding remain. Understanding of energy and carbon exchange between terrestrial ecosystems and the atmosphere can be improved through direct observations and experiments, as well as through modeling activities. Land surface/ecosystem models have become important tools for extrapolating local observations and understanding to much larger terrestrial regions. They are also valuable tools to test hypothesis on ecosystem functioning. Funded by NASA under the auspices of the LBA (the Large-Scale Biosphere–Atmosphere Experiment in Amazonia), the LBA Data Model Intercomparison Project (LBA-DMIP) uses a comprehensive data set from an observational network of flux towers across the Amazon, and an ecosystem modeling community engaged in ongoing studies using a suite of different land surface and terrestrial ecosystem models to understand Amazon forest function. Here an overview of this project is presented accompanied by a description of the measurement sites, data, models and protocol

(Table 1) Summary of biostratigraphic and magnetostratigraphic datum levels for ODP Leg 127/128 sites

This paper summarizes the biostratigraphic and magnetostratigraphic results from the recovery of holes drilled during Legs 127 and 128 in the Sea of Japan. Siliceous microfossils (i.e., diatoms, radiolarians, silicoflagellates, and ebridians) were most useful as biostratigraphic datum markers in the upper part of the section (Pliocene-Pleistocene), as was the magnetostratigraphy. Time series of other biostratigraphic, climatostratigraphic, and lithostratigraphic markers indicate that a high-resolution picture of the late Pliocene-Pleistocene oceanographic and climatic history of the Sea of Japan is possible. These data include coiling direction changes in Neogloboquadrina pachyderma, oxygen isotopes, percent opal, and alternating dark/light rhythms. Although the magnetostratigraphy was somewhat ambiguous in corroborating age determinations in the older part of the sections, calcareous microfossils and foraminifers indicate that some of the holes penetrated as far back in time as the early Miocene. These data provide a new time frame for theories on the age of formation and early history of the Sea of Japan