Diurnal inhibition of NMDA-EPSCs at rat hippocampal mossy fibre synapses through orexin-2 receptors.

Diurnal release of the orexin neuropeptides orexin-A (Ox-A, hypocretin-1) and orexin-B (Ox-B, hypocretin-2) stabilises arousal, regulates energy homeostasis and contributes to cognition and learning. However, whether cellular correlates of brain plasticity are regulated through orexins, and whether they do so in a time-of-day-dependent manner, has never been assessed. Immunohistochemically we found sparse but widespread innervation of hippocampal subfields through Ox-A- and Ox-B-containing fibres in young adult rats. The actions of Ox-A were studied on NMDA receptor (NMDAR)-mediated excitatory synaptic transmission in acute hippocampal slices prepared around the trough (Zeitgeber time (ZT) 4-8, corresponding to 4-8 h into the resting phase) and peak (ZT 23) of intracerebroventricular orexin levels. At ZT 4-8, exogenous Ox-A (100 nm in bath) inhibited NMDA receptor-mediated excitatory postsynaptic currents (NMDA-EPSCs) at mossy fibre (MF)-CA3 (to 55.6 ± 6.8% of control, P = 0.0003) and at Schaffer collateral-CA1 synapses (70.8 ± 6.3%, P = 0.013), whereas it remained ineffective at non-MF excitatory synapses in CA3. Ox-A actions were mediated postsynaptically and blocked by the orexin-2 receptor (OX2R) antagonist JNJ10397049 (1 μm), but not by orexin-1 receptor inhibition (SB334867, 1 μm) or by adrenergic and cholinergic antagonists. At ZT 23, inhibitory effects of exogenous Ox-A were absent (97.6 ± 2.9%, P = 0.42), but reinstated (87.2 ± 3.3%, P = 0.002) when endogenous orexin signalling was attenuated for 5 h through i.p. injections of almorexant (100 mg kg(-1)), a dual orexin receptor antagonist. In conclusion, endogenous orexins modulate hippocampal NMDAR function in a time-of-day-dependent manner, suggesting that they may influence cellular plasticity and consequent variations in memory performance across the sleep-wake cycle

c-Jun N-terminal kinase has a key role in Alzheimer disease synaptic dysfunction in vivo.

Altered synaptic function is considered one of the first features of Alzheimer disease (AD). Currently, no treatment is available to prevent the dysfunction of excitatory synapses in AD. Identification of the key modulators of synaptopathy is of particular significance in the treatment of AD. We here characterized the pathways leading to synaptopathy in TgCRND8 mice and showed that c-Jun N-terminal kinase (JNK) is activated at the spine prior to the onset of cognitive impairment. The specific inhibition of JNK, with its specific inhibiting peptide D-JNKI1, prevented synaptic dysfunction in TgCRND8 mice. D-JNKI1 avoided both the loss of postsynaptic proteins and glutamate receptors from the postsynaptic density and the reduction in size of excitatory synapses, reverting their dysfunction. This set of data reveals that JNK is a key signaling pathway in AD synaptic injury and that its specific inhibition offers an innovative therapeutic strategy to prevent spine degeneration in AD

Estimation of Carbon Sequestration by Combining Remote Sensing and Net Ecosystem Exchange Data for Northern Mixed-Grass Prairie and Sagebrush–Steppe Ecosystems

Carbon sequestration was estimated a northern mixed-grass prairie site and a sagebrush–steppe site in southeastern Wyoming using an approach that integrates remote sensing, CO2 flux measurements, and meteorological data. Net ecosystem exchange (NEE) of CO2 was measured using aircraft and ground flux techniques and was linearly related to absorbed photosynthetically active radiation (APAR). The slope of this relationship is the radiation use efficiency (ε = 0.51 g C/MJ APAR); there were no significant differences in the regression coefficients between the two sites. Furthermore, ecosystem chamber measurements of total respiration in 1998 and 1999 were used to develop a functional relationship with daily average temperature; the Q10 of the relationship was 2.2. Using the Advanced Very High Resolution radiometer. Normalized Difference Vegetation Index and meteorological data, annual gross primary production and respiration were calculated from 1995 to 1999 for the two sites. Overall, the sagebrush– steppe site was a net carbon sink, whereas the northern mixed-grass prairie site was in carbon balance. There was no significant relationship between NEE and APAR for a coniferous forest site, indicating this method for scaling up CO2 flux data may be only applicable to rangeland ecosystems. The combination of remote sensing with data from CO2 flux networks can be used to estimate carbon sequestration regionally in rangeland ecosystems

Lacustrine leaf wax hydrogen isotopes indicate strong regional climate feedbacks in Beringia since the last ice age

The Late-Quaternary climate of Beringia remains unresolved despite the region\u27s role in modulating glacial-interglacial climate and as the likely conduit for human dispersal into the Americas. Here, we investigate Beringian temperature change using an ~32,000-year lacustrine record of leaf wax hydrogen isotope ratios (δ2Hwax) from Arctic Alaska. Based on Monte Carlo iterations accounting for multiple sources of uncertainty, the reconstructed summertime temperatures were ~3 oC colder (range: -8 to +3 oC) during the Last Glacial Maximum (LGM; 21-25 ka) than the pre-industrial era (PI; 2-0.1 ka). This ice-age summer cooling is substantially smaller than in other parts of the Arctic, reflecting altered atmospheric circulation and increased continentality which weakened glacial cooling in the region. Deglacial warming was punctuated by abrupt events that are largely synchronous with events seen in Greenland ice cores that originate in the North Atlantic but which are also controlled locally, such as by the opening of the Bering Strait between 13.4 and 11 ka. Our reconstruction, together with climate modeling experiments, indicates that Beringia responds more strongly to North Atlantic freshwater forcing under modern-day, open-Bering Strait conditions than under glacial conditions. Furthermore, a 2 oC increase (Monte Carlo range: -1 to +5 oC) over the anthropogenic era reverses a 6 oC decline (Monte Carlo range: -10 to 0 oC) through the Holocene, indicating that recent warming in Arctic Alaska has not surpassed peak Holocene summer warmth

Identifying Archaeological Bone via Non-Destructive ZooMS and the Materiality of Symbolic Expression: Examples from Iroquoian Bone Points.

Today, practical, functional and symbolic choices inform the selection of raw materials for worked objects. In cases where we can discern the origin of worked bone, tooth, ivory and antler objects in the past, we assume that similar choices are being made. However, morphological species identification of worked objects is often impossible due to the loss of identifying characteristics during manufacture. Here, we describe a novel non-destructive ZooMS (Zooarchaeology by Mass Spectrometry) method which was applied to bone points from Pre-Contact St. Lawrence Iroquoian village sites in southern Quebec, Canada. The traditional ZooMS technique requires destructive analysis of a sample, which can be problematic when dealing with artefacts. Here we instead extracted proteins from the plastic bags in which the points had been stored. ZooMS analysis revealed hitherto unexpected species, notably black bear (Ursus americanus) and human (Homo sapiens sapiens), used in point manufacture. These surprising results (confirmed through genomic sequencing) highlight the importance of advancing biomolecular research in artefact studies. Furthermore, they unexpectedly and exceptionally allow us to identify and explore the tangible, material traces of the symbolic relationship between bears and humans, central to past and present Iroquoian cosmology and mythology

The prion protein family member Shadoo induces spontaneous ionic currents in cultured cells

Some mutant forms of the cellular prion protein (PrPC) carrying artificial deletions or point mutations associated with familial human prion diseases are capable of inducing spontaneous ionic currents across the cell membrane, conferring hypersensitivity to certain antibiotics to a wide range of cultured cells and primary cerebellar granular neurons (CGNs). These effects are abrogated when the wild type (WT) form is co-expressed, suggesting that they might be related to a physiological activity of PrPC. Interestingly, the prion protein family member Shadoo (Sho) makes cells hypersensitive to the same antibiotics as mutant PrP-s, an effect that is diminished by the co-expression of WT-PrP. Here, we report that Sho engages in another mutant PrP-like activity: it spontaneously induces large ionic currents in cultured SH-SY5Y cells, as detected by whole-cell patch clamping. These currents are also decreased by the co-expression of WT-PrP. Furthermore, deletion of the N-terminal (RXXX)8 motif of Sho, mutation of the eight arginine residues of this motif to glutamines, or replacement of the hydrophobic domain by that of PrP, also diminish Sho-induced ionic currents. Our results suggest that the channel activity that is also characteristic to some pathogenic PrP mutants may be linked to a physiological function of Sho

The three hundred project: thermodynamical properties, shocks and gas dynamics in simulated galaxy cluster filaments and their surroundings

Using cosmological simulations of galaxy cluster regions from The Three Hundred project we study the nature of gas in filaments feeding massive clusters. By stacking the diffuse material of filaments throughout the cluster sample, we measure average gas properties such as density, temperature, pressure, entropy and Mach number and construct one-dimensional profiles for a sample of larger, radially-oriented filaments to determine their characteristic features as cosmological objects. Despite the similarity in velocity space between the gas and dark matter accretion patterns onto filaments and their central clusters, we confirm some differences, especially concerning the more ordered radial velocity dispersion of dark matter around the cluster and the larger accretion velocity of gas relative to dark matter in filaments. We also study the distribution of shocked gas around filaments and galaxy clusters, showing that the surrounding shocks allow an efficient internal transport of material, suggesting a laminar infall. The stacked temperature profile of filaments is typically colder towards the spine, in line with the cosmological rarefaction of matter. Therefore, filaments are able to isolate their inner regions, maintaining lower gas temperatures and entropy. Finally, we study the evolution of the gas density-temperature phase diagram of our stacked filament, showing that filamentary gas does not behave fully adiabatically through time but it is subject to shocks during its evolution, establishing a characteristic z = 0, entropy-enhanced distribution at intermediate distances from the spine of about 1 - 2 $h^{-1}$ Mpc for a typical galaxy cluster in our sample.Comment: 16 pages, 13 figures. Accepted for publication in MNRA

Subbarrel patterns in somatosensory cortical barrels can emerge from local dynamic instabilities

Complex spatial patterning, common in the brain as well as in other biological systems, can emerge as a result of dynamic interactions that occur locally within developing structures. In the rodent somatosensory cortex, groups of neurons called "barrels" correspond to individual whiskers on the contralateral face. Barrels themselves often contain subbarrels organized into one of a few characteristic patterns. Here we demonstrate that similar patterns can be simulated by means of local growth-promoting and growth-retarding interactions within the circular domains of single barrels. The model correctly predicts that larger barrels contain more spatially complex subbarrel patterns, suggesting that the development of barrels and of the patterns within them may be understood in terms of some relatively simple dynamic processes. We also simulate the full nonlinear equations to demonstrate the predictive value of our linear analysis. Finally, we show that the pattern formation is robust with respect to the geometry of the barrel by simulating patterns on a realistically shaped barrel domain. This work shows how simple pattern forming mechanisms can explain neural wiring both qualitatively and quantitatively even in complex and irregular domains. © 2009 Ermentrout et al