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      • Wide-field and two-photon imaging of brain activity with voltage- and calcium-sensitive dyes.

        Homma, Ryota,Baker, Bradley J,Jin, Lei,Garaschuk, Olga,Konnerth, Arthur,Cohen, Lawrence B,Zecevic, Dejan Royal Society of London 2009 Philosophical transactions. Biological sciences Vol.364 No.1529

        <P>This review presents three examples of using voltage- or calcium-sensitive dyes to image the activity of the brain. Our aim is to discuss the advantages and disadvantages of each method with particular reference to its application to the study of the brainstem. Two of the examples use wide-field (one-photon) imaging; the third uses two-photon scanning microscopy. Because the measurements have limited signal-to-noise ratio, the paper also discusses the methodological aspects that are critical for optimizing the signal. The three examples are the following. (i) An intracellularly injected voltage-sensitive dye was used to monitor membrane potential in the dendrites of neurons in in vitro preparations. These experiments were directed at understanding how individual neurons convert complex synaptic inputs into the output spike train. (ii) An extracellular, bath application of a voltage-sensitive dye was used to monitor population signals from different parts of the dorsal brainstem. We describe recordings made during respiratory activity. The population signals indicated four different regions with distinct activity correlated with inspiration. (iii) Calcium-sensitive dyes can be used to label many individual cells in the mammalian brain. This approach, combined with two-photon microscopy, made it possible to follow the spike activity in an in vitro brainstem preparation during fictive respiratory rhythms. The organic voltage- and ion-sensitive dyes used today indiscriminatively stain all of the cell types in the preparation. A major effort is underway to develop fluorescent protein sensors of activity for selectively staining individual cell types.</P>

      • NMDA receptor-dependent long-term potentiation comprises a family of temporally overlapping forms of synaptic plasticity that are induced by different patterns of stimulation

        Park, Pojeong,Volianskis, Arturas,Sanderson, Thomas M.,Bortolotto, Zuner A.,Jane, David E.,Zhuo, Min,Kaang, Bong-Kiun,Collingridge, Graham L. Royal Society of London 2014 Philosophical transactions. Biological sciences Vol.369 No.1633

        N-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) is extensively studied since it is believed to use the same molecular mechanisms that are required for many forms of learning and memory. Unfortunately, many controversies exist, not least the seemingly simple issue concerning the locus of expression of LTP. Here, we review our recent work and some of the extensive literature on this topic and present new data that collectively suggest that LTP can be explained, during its first few hours, by the coexistence of at least three mechanistically distinct processes that are all triggered by the synaptic activation of NMDARs.

      • Long-term depression-inducing stimuli promote cleavage of the synaptic adhesion molecule NGL-3 through NMDA receptors, matrix metalloproteinases and presenilin/gamma-secretase

        Lee, Hyejin,Lee, Eun-Jae,Song, Yoo Sung,Kim, Eunjoon Royal Society of London 2014 Philosophical transactions. Biological sciences Vol.369 No.1633

        Long-term depression (LTD) reduces the functional strength of excitatory synapses through mechanisms that include the removal of AMPA glutamate receptors from the postsynaptic membrane. LTD induction is also known to result in structural changes at excitatory synapses, including the shrinkage of dendritic spines. Synaptic adhesion molecules are thought to contribute to the development, function and plasticity of neuronal synapses largely through their trans-synaptic adhesions. However, little is known about how synaptic adhesion molecules are altered during LTD. We report here that NGL-3 (netrin-G ligand-3), a postsynaptic adhesion molecule that trans-synaptically interacts with the LAR family of receptor tyrosine phosphatases and intracellularly with the postsynaptic scaffolding protein PSD-95, undergoes a proteolytic cleavage process. NGL-3 cleavage is induced by NMDA treatment in cultured neurons and low-frequency stimulation in brain slices and requires the activities of NMDA glutamate receptors, matrix metalloproteinases (MMPs) and presenilin/gamma-secretase. These results suggest that NGL-3 is a novel substrate of MMPs and gamma-secretase and that NGL-3 cleavage may regulate synaptic adhesion during LTD.

      • Forecasting phenology under global warming.

        Ibá,ñ,ez, Iné,s,Primack, Richard B,Miller-Rushing, Abraham J,Ellwood, Elizabeth,Higuchi, Hiroyoshi,Lee, Sang Don,Kobori, Hiromi,Silander, John A Royal Society of London 2010 Philosophical transactions. Biological sciences Vol.365 No.1555

        <P>As a consequence of warming temperatures around the world, spring and autumn phenologies have been shifting, with corresponding changes in the length of the growing season. Our understanding of the spatial and interspecific variation of these changes, however, is limited. Not all species are responding similarly, and there is significant spatial variation in responses even within species. This spatial and interspecific variation complicates efforts to predict phenological responses to ongoing climate change, but must be incorporated in order to build reliable forecasts. Here, we use a long-term dataset (1953-2005) of plant phenological events in spring (flowering and leaf out) and autumn (leaf colouring and leaf fall) throughout Japan and South Korea to build forecasts that account for these sources of variability. Specifically, we used hierarchical models to incorporate the spatial variability in phenological responses to temperature to then forecast species' overall and site-specific responses to global warming. We found that for most species, spring phenology is advancing and autumn phenology is getting later, with the timing of events changing more quickly in autumn compared with the spring. Temporal trends and phenological responses to temperature in East Asia contrasted with results from comparable studies in Europe, where spring events are changing more rapidly than are autumn events. Our results emphasize the need to study multiple species at many sites to understand and forecast regional changes in phenology.</P>

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