Microglia sense neuronal activity via GABA in the early postnatal hippocampus

Microglia, the resident macrophages in the central nervous system, express receptors for classical neurotransmitters, such as γ-aminobutyric acid (GABA) and glutamate, suggesting that they sense synaptic activity. To detect microglial Ca(2+) responses to neuronal activity, we generate transgenic mouse lines expressing the fluorescent Ca(2+) indicator GCaMP6m, specifically in microglia and demonstrate that electrical stimulation of the Schaffer collateral pathway results in microglial Ca(2+) responses in early postnatal but not adult hippocampus. Preceding the microglial responses, we also observe similar Ca(2+) responses in astrocytes, and both are sensitive to tetrodotoxin. Blocking astrocytic glutamate uptake or GABA transport abolishes stimulation-induced microglial responses as well as antagonizing the microglial GABA(B) receptor. Our data, therefore, suggest that the neuronal activity-induced glutamate uptake and the release of GABA by astrocytes trigger the activation of GABA(B) receptors in microglia. This neuron, astrocyte, and microglia communication pathway might modulate microglial activity in developing neuronal networks

Hydrographic influence on the spawning habitat suitability of western Baltic cod (Gadus morhua)

Recruitment variability of marine fish is influenced by the reproductive potential of the stock (i.e. stock characteristics and abundance) and the survival of early life stages, mediated by environmental conditions of both a physical (water temperature, salinity and oxygen conditions, ocean currents) and a biological nature (i.e. food, predators). The objective of this study is to assess the importance of variability in environmental conditions within different western Baltic cod spawning grounds for egg survival. Habitat identification was based on environmental threshold levels for egg survival and development and ambient hydrographical conditions at different times during the spawning season. The long-term resolution of environmental conditions allowing survival of western Baltic cod eggs indicates that favourable conditions predominantly occurred during the late spawning season in April/May, while minimum survival rates could be expected from January to March. Unsuitable time periods and habitats exhibiting the highest mortality rates are exclusively characterized by ambient water temperatures below the critical survival threshold. Despite the strong influence of water temperature on habitat suitability, the impact of habitat suitability on recruitment was not clearly defined, suggesting that other mechanisms regulate year class strength

Modeling transport and fate of riverine dissolved organic carbon in the Arctic Ocean

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 23 (2009): GB4006, doi:10.1029/2008GB003396.The spatial distribution and fate of riverine dissolved organic carbon (DOC) in the Arctic may be significant for the regional carbon cycle but are difficult to fully characterize using the sparse observations alone. Numerical models of the circulation and biogeochemical cycles of the region can help to interpret and extrapolate the data and may ultimately be applied in global change sensitivity studies. Here we develop and explore a regional, three-dimensional model of the Arctic Ocean in which, for the first time, we explicitly represent the sources of riverine DOC with seasonal discharge based on climatological field estimates. Through a suite of numerical experiments, we explore the distribution of DOC-like tracers with realistic riverine sources and a simple linear decay to represent remineralization through microbial degradation. The model reproduces the slope of the DOC-salinity relationship observed in the eastern and western Arctic basins when the DOC tracer lifetime is about 10 years, consistent with published inferences from field data. The new empirical parameterization of riverine DOC and the regional circulation and biogeochemical model provide new tools for application in both regional and global change studies.I.M.M. and M.J.F. are grateful to National Science Foundation for financial support

Sex-specific microglia state in the neuroligin-4 knock-out mouse model of autism spectrum disorder

Neuroligin-4 (NLGN4) loss-of-function mutations are associated with monogenic heritable autism spectrum disorder (ASD) and cause alterations in both synaptic and behavioral phenotypes. Microglia, the resident CNS macrophages, are implicated in ASD development and progression. Here we studied the impact of NLGN4 loss in a mouse model, focusing on microglia phenotype and function in both male and female mice. NLGN4 depletion caused lower microglia density, less ramified morphology, reduced response to injury and purinergic signaling specifically in the hippocampal CA3 region predominantly in male mice. Proteomic analysis revealed disrupted energy metabolism in male microglia and provided further evidence for sexual dimorphism in the ASD associated microglial phenotype. In addition, we observed impaired gamma oscillations in a sex-dependent manner. Lastly, estradiol application in male NLGN4(-/-) mice restored the altered microglial phenotype and function. Together, these results indicate that loss of NLGN4 affects not only neuronal network activity, but also changes the microglia state in a sex-dependent manner that could be targeted by estradiol treatment

A decade of acoustic thermometry in the North Pacific Ocean

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94643/1/jgrc11250.pd

Predicting climate change using response theory: global averages and spatial patterns

The provision of accurate methods for predicting the climate response to anthropogenic and natural forcings is a key contemporary scientific challenge. Using a simplified and efficient open-source general circulation model of the atmosphere featuring O(105105) degrees of freedom, we show how it is possible to approach such a problem using nonequilibrium statistical mechanics. Response theory allows one to practically compute the time-dependent measure supported on the pullback attractor of the climate system, whose dynamics is non-autonomous as a result of time-dependent forcings. We propose a simple yet efficient method for predicting—at any lead time and in an ensemble sense—the change in climate properties resulting from increase in the concentration of CO22 using test perturbation model runs. We assess strengths and limitations of the response theory in predicting the changes in the globally averaged values of surface temperature and of the yearly total precipitation, as well as in their spatial patterns. The quality of the predictions obtained for the surface temperature fields is rather good, while in the case of precipitation a good skill is observed only for the global average. We also show how it is possible to define accurately concepts like the inertia of the climate system or to predict when climate change is detectable given a scenario of forcing. Our analysis can be extended for dealing with more complex portfolios of forcings and can be adapted to treat, in principle, any climate observable. Our conclusion is that climate change is indeed a problem that can be effectively seen through a statistical mechanical lens, and that there is great potential for optimizing the current coordinated modelling exercises run for the preparation of the subsequent reports of the Intergovernmental Panel for Climate Change

Interdomain Interactions Control Ca2+-Dependent Potentiation in the Cation Channel TRPV4

Several Ca2+-permeable channels, including the non-selective cation channel TRPV4, are subject to Ca2+-dependent facilitation. Although it has been clearly demonstrated in functional experiments that calmodulin (CaM) binding to intracellular domains of TRP channels is involved in this process, the molecular mechanism remains elusive. In this study, we provide experimental evidence for a comprehensive molecular model that explains Ca2+-dependent facilitation of TRPV4. In the resting state, an intracellular domain from the channel N terminus forms an autoinhibitory complex with a C-terminal domain that includes a high-affinity CaM binding site. CaM binding, secondary to rises in intracellular Ca2+, displaces the N-terminal domain which may then form a homologous interaction with an identical domain from a second subunit. This represents a novel potentiation mechanism that may also be relevant in other Ca2+-permeable channels

Modeling Recent Climate Variability in the Arctic Ocean

Dramatic changes in the circulation of sea ice and the upper layers of the Arctic Ocean have been reported during the last decade. Similar variability is modeled using a regional, coupled ice-ocean model. Realistic atmospheric forcing elds for 1979-93 are the only interannual signal prescribed in the model. Our results show large-scale changes in sea ice and oceanic conditions when comparing results for the late 1970s / early 1980s and the 1990s. We hypothesize that these changes are in response to even larger scale atmospheric variability in the Northern Hemisphere that can be de ned as either the Arctic Oscillation or the North Atlantic Oscillation. Agreement between the direction and scale of change in the model and observations, in the absence of interannual forcing from the global ocean thermohaline circulation, suggests that the atmospheric variability by itself is su cient to produce basin-scale changes in the Arctic Ocean and sea ice system