source_doi stringlengths 13 57 | source_mag_paper_id int64 490k 157M | source_abstract stringlengths 8 10.7k | target_doi stringlengths 14 27 | target_summary stringlengths 42 889 |
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10.1046/j.1365-2826.2003.00960.x | 26,467,835 | Abstract Cocaine‐ and amphetamine‐regulated transcript (CART) is present in a number of hypothalamic nuclei. Besides actions in circuits regulating feeding behaviour and stress responses, the hypothalamic functions of CART are largely unknown. We report that CART immunoreactivity is present in hypothalamic neuroendocri... | 10.1038/nrn2493 | This study demonstrated the presence of CART peptides in the portal blood, which is fundamental to a role for them in endocrine regulation. |
10.1046/j.1365-2826.1997.00651.x | 41,310,362 | CART peptide specific polyclonal antisera were raised in rabbits. The antisera were raised to CART peptide fragments that span most of the predicted CART protein. The specificity of each antisera was demonstrated by blockade of immunostaining by the immunizing peptide but not by the other CART peptide fragments. In the... | 10.1038/nrn2493 | This paper and reference 14 presented a detailed description of CART peptide distribution. The distribution suggested many roles for the CART system in endocrine function, stress and feeding. |
10.2337/diabetes.50.9.2157 | 42,500,894 | Cocaine- and amphetamine-regulated transcript (CART) inhibits feeding and induces the expression of c-Fos in hypothalamic areas implicated in appetite regulation. Furthermore, the CART peptide is found in neurons regulating sympathetic outflow, which in turn play an integral role in regulating body temperature and ener... | 10.1038/nrn2493 | This paper demonstrated a relationship between a mutation in the CART gene and obesity among family members. The mutation disrupts CART peptide processing and levels (see reference 74 |
10.1046/j.1432-1327.2000.01565.x | 58,527,430 | In neurons, calcium ions control gene transcription induced by synaptic activity. The states and histories of neuronal activity are represented by a calcium code that comprises the site of calcium entry, and the amplitude, duration and spatial properties of signal‐evoked calcium transients. The calcium code is used to ... | 10.1038/nrn3531 | This paper was the first to suggest that nuclear calcium functions as a common regulator of different forms of transcription-dependent adaptations in the nervous system. |
10.1126/science.3775383 | 20,778,488 | Both long-term and short-term sensitization of the gill and siphon withdrawal reflex in Aplysia involve facilitation of the monosynaptic connections between the sensory and motor neurons. To analyze the relationship between these two forms of synaptic facilitation at the cellular and molecular level, this monosynaptic ... | 10.1038/nrn3531 | This is a landmark paper that provided evidence for the requirement of RNA and protein synthesis for long-lasting synaptic and behavioural plasticity. |
10.1126/science.8066450 | 62,101,841 | Repeated high-frequency trains of stimuli induce long-term potentiation (LTP) in the CA1 region that persists for up to 8 hours in hippocampal slices and for days in intact animals. This long time course has made LTP an attractive model for certain forms of long-term memory in the mammalian brain. A hallmark of long-te... | 10.1038/nrn3531 | This study identified the transcription dependency of late-phase long-term potentiation in the rat hippocampus. The close parallels with the transcription dependency of long-term facilitation in A. californica (reference 14) revealed a commonality between mammals and invertebrates, suggesting the possibility of similar... |
10.1126/scisignal.2003598 | 16,919,027 | Blocking nuclear calcium signaling reversibly inhibits long-term memory formation in flies. | 10.1038/nrn3531 | This study provided the first evidence for a learning-associated nuclear calcium signal in vivo and identified nuclear calcium as an evolutionary conserved signal required for long-term memory formation. |
10.1126/science.8097060 | 60,078,228 | Calcium ions (Ca 2+ ) act as an intracellular second messenger and can enter neurons through various ion channels. Influx of Ca 2+ through distinct types of Ca 2+ channels may differentially activate biochemical processes. N -Methyl-D-aspartate (NMDA) receptors and L-type Ca 2+ channels, two major sites of Ca 2+ entry ... | 10.1038/nrn3531 | This study identified calcium as the principal second messenger in the control of neuronal activity-dependent gene expression in hippocampal neurons and defined two distinct signalling pathways that couple calcium entry into neurons to the activation of transcription. |
10.1152/jn.1994.72.1.471 | 10,314,137 | 1. We investigated the effects of metabotropic glutamate (mGlu) receptor activation on intracellular Ca2+ concentration ([Ca2+]i) in the soma and dendrites of hippocampal CA1 pyramidal neurons. Changes in [Ca2+]i were measured using confocal imaging simultaneously with whole-cell recording techniques. Differences in [C... | 10.1038/nrn3531 | The authors were the first to report calcium waves in hippocampal dendrites that were triggered by a focally applied metabotropic glutamate receptor agonist, suggesting a role for IP3 receptor-mediated calcium release in wave initiation and propagation. |
10.1126/science.281.5382.1505 | 38,581,811 | Recruitment of the coactivator, CREB binding protein (CBP), by signal-regulated transcription factors, such as CREB [adenosine 3′,5′-monophosphate (cAMP) response element binding protein], is critical for stimulation of gene expression. The mouse pituitary cell line AtT20 was used to show that the CBP recruitment step ... | 10.1038/nrn3531 | This study showed that CBP, a co-activator that interacts with CREB and numerous other transcription factors, is a target of nuclear calcium–CaMKIV signalling. Through recruitment of CBP, nuclear calcium inducibility may be conferred to many transcription factors, providing a mechanism for the regulation of a large num... |
10.1523/jneurosci.1022-04.2004 | 81,791,668 | The neuronal response to a Ca 2+ stimulus is a complex process involving direct Ca 2+ /calmodulin (CaM) actions as well as secondary activation of multiple signaling pathways such as cAMP and ERK (extracellular signal-regulated kinase). These signals can act in both the cytoplasm and the nucleus to control gene express... | 10.1038/nrn3531 | Using transgenic mice that express an inhibitor of nuclear calcium/calmodulin signalling in the forebrain, the authors provided the first evidence for a role of nuclear calcium signalling in the formation of long-term memory. |
10.1523/jneurosci.5019-04.2005 | 82,902,030 | The mechanism by which physiological synaptic NMDA receptor activity promotes neuronal survival is not well understood. Here, we show that that an episode of synaptic activity can promote neuroprotection for a long time after that activity has ceased. This long-lasting or “late phase” of neuroprotection is dependent on... | 10.1038/nrn3531 | This paper was the first to show a role for nuclear calcium signalling in acquired neuroprotection. |
10.1126/science.276.5313.734 | 62,606,536 | Over three decades of molecular-phylogenetic studies, researchers have compiled an increasingly robust map of evolutionary diversification showing that the main diversity of life is microbial, distributed among three primary relatedness groups or domains: Archaea, Bacteria, and Eucarya. The general properties of repres... | 10.1038/nrmicro3400 | An early review summarizing molecular phylogenetic methods for studying microbial ecosystems. |
10.1073/pnas.0605127103 | 104,393,044 | The evolution of marine microbes over billions of years predicts that the composition of microbial communities should be much greater than the published estimates of a few thousand distinct kinds of microbes per liter of seawater. By adopting a massively parallel tag sequencing strategy, we show that bacterial communit... | 10.1038/nrmicro3400 | This study was the first to recognize and describe the rare biosphere with the use of HTS. |
10.1073/pnas.0908284106 | 20,214,642 | Understanding the role of microbes in the oceans has focused on taxa that occur in high abundance; yet most of the marine microbial diversity is largely determined by a long tail of low-abundance taxa. This rare biosphere may have a cosmopolitan distribution because of high dispersal and low loss rates, and possibly re... | 10.1038/nrmicro3400 | This study explores the ecology, taxonomy and biogeographic trends of rare marine microorganisms. |
10.1038/ismej.2012.50 | 58,634,092 | Abstract Next-generation sequencing technologies have led to recognition of a so-called ‘rare biosphere’. These microbial operational taxonomic units (OTUs) are defined by low relative abundance and may be specifically adapted to maintaining low population sizes. We hypothesized that mining of low-abundance next-genera... | 10.1038/nrmicro3400 | This study used phylogenetic mining of HTS data to identify taxonomic blind spots through targeted gene recovery. |
10.1126/science.1174012 | 42,526,537 | Monitoring Massive Microbial Dispersal Quantifying the relative influence of present-day environmental conditions and geological history on the spatial distribution of species represents a major challenge in microbial ecology. Ecological approaches to distinguish between these two biogeographic controls are limited by ... | 10.1038/nrmicro3400 | This study demonstrates thermophilic bacterial immigration and preservation within Arctic sediment and identifies influences on community composition. |
10.1038/ismej.2011.162 | 99,131,860 | Abstract Robust seasonal dynamics in microbial community composition have previously been observed in the English Channel L4 marine observatory. These could be explained either by seasonal changes in the taxa present at the L4 site, or by the continuous modulation of abundance of taxa within a persistent microbial comm... | 10.1038/nrmicro3400 | Deep sequencing of a single time point, compared to a 6-year time series, resulted in the identification of recruitment from the rare biosphere or microbial seed bank rather than extinction and recolonization. |
10.1073/pnas.1217767110 | 83,479,694 | Do bacterial taxa demonstrate clear endemism, like macroorganisms, or can one site’s bacterial community recapture the total phylogenetic diversity of the world’s oceans? Here we compare a deep bacterial community characterization from one site in the English Channel (L4-DeepSeq) with 356 datasets from the Internationa... | 10.1038/nrmicro3400 | Single-location (English Channel station L4) deep sequencing shows substantial taxonomic overlap with global marine sampling and strongly suggests that there is a rich and persistent microbial seed bank. |
10.1523/jneurosci.1183-06.2006 | 103,783,884 | Developing neurons have greater capacity in experience-dependent plasticity than adult neurons but the molecular mechanism is not well understood. Here we report a developmentally regulated long-term synaptic plasticity through actin-dependent activation of presynaptic silent synapses in cultured hippocampal neurons. L... | 10.1038/nrn2373 | This paper detailed how repetitive neuronal stimulation converts presynaptic silent synapses into functional release sites through a process that is dependent on actin polymerization in developing neurons. |
10.1523/jneurosci.2015-07.2007 | 38,871,886 | Physiological and morphological alterations occur with long-term synaptic modifications, such as long-term potentiation (LTP) and long-term depression (LTD), but whether these two processes are independent or interactive is unclear. It is also unknown whether or how morphological modifications, like spine remodeling, m... | 10.1038/nrn2373 | This paper demonstrated that there is a clear dissociation between functional LTD and structural LTD (spine shrinkage). |
10.1523/jneurosci.3918-05.2006 | 122,960,497 | The changes in synaptic morphology and receptor content that underlie neural plasticity are poorly understood. Here, we use a pH-sensitive green fluorescent protein to tag recombinant glutamate receptors and monitor their dynamics onto dendritic spine surfaces. We show that chemically induced long-term potentiation (ch... | 10.1038/nrn2373 | This study showed that synaptic incorporation of the GluR1 cytosolic C terminus is required to permit a stable increase in spine size upon LTP induction. |
10.1073/pnas.162223099 | 100,736,912 | Programmed −1 ribosomal frameshifting is necessary for translation of the polymerase genes of many viruses. In addition to the consensus elements in the mRNA around the frameshift site, we found previously that frameshifting on Barley yellow dwarf virus RNA requires viral sequence located four kilobases downstream. By ... | 10.1038/nrmicro3288 | This paper provides the first experimental evidence for a long-range interaction that facilitates frameshifting. |
10.1101/gad.1444206 | 81,114,430 | The mechanisms of RNA replication of plus-strand RNA viruses are still unclear. Here, we identified the first promoter element for RNA synthesis described in a flavivirus. Using dengue virus as a model, we found that the viral RdRp discriminates the viral RNA by specific recognition of a 5′ element named SLA. We demons... | 10.1038/nrmicro3288 | This study reports the identification of a 5′-proximal RNA element that is recognized by the viral RdRp and proposes a model that involves the relocation of the RdRp to the 3′-terminus via long-range RNA–RNA base pairing. |
10.1126/science.2321027 | 83,489,406 | Molecular excitation by the simultaneous absorption of two photons provides intrinsic three-dimensional resolution in laser scanning fluorescence microscopy. The excitation of fluorophores having single-photon absorption in the ultraviolet with a stream of strongly focused subpicosecond pulses of red laser light has ma... | 10.1038/nrn2338 | This study provided the first demonstration that two-photon excitation can be used to image fluorescently stained living cells and cellular substructures. |
10.1073/pnas.1232232100 | 20,580,675 | Two-photon calcium imaging is a powerful means for monitoring the activity of distinct neurons in brain tissue in vivo . In the mammalian brain, such imaging studies have been restricted largely to calcium recordings from neurons that were individually dye-loaded through microelectrodes. Previous attempts to use membra... | 10.1038/nrn2338 | This was the first study to image Ca 2+ transients in vivo from neuronal populations bulk-loaded with membrane-permeable Ca 2+ -indicator dyes. Most commercially available Ca 2+ -indicator dyes were tried. |
10.1073/pnas.0506029102 | 125,138,857 | Neural activity manifests itself as complex spatiotemporal activation patterns in cell populations. Even for local neural circuits, a comprehensive description of network activity has been impossible so far. Here we demonstrate that two-photon calcium imaging of bulk-labeled tissue permits dissection of local input and... | 10.1038/nrn2338 | Using simultaneous imaging and targeted electrical recordings, this study showed that it was possible to infer electrical activity with single-cell and single-AP accuracy from Ca 2+ transients measured in populations of bulk-loaded neurons (see also references 35, 103 and 155). |
10.1073/pnas.0604791103 | 41,586,247 | The image quality of a two-photon microscope is often degraded by wavefront aberrations induced by the specimen. We demonstrate here that resolution and signal size in two-photon microcopy can be substantially improved, even in living biological specimens, by adaptive wavefront correction based on sensing the wavefront... | 10.1038/nrn2338 | This study showed how both imaging resolution and signal size were improved by measuring beam wavefront distortions and compensating for these distortions using adaptive optics. This technology will be of great benefit to imaging in preparations in which both intact dura and skull are required. |
10.1126/science.1109886 | 19,368,192 | Signaling by heterotrimeric GTP-binding proteins (G proteins) drives numerous cellular processes. The number of G protein molecules activated by a single membrane receptor is a determinant of signal amplification, although in most cases this parameter remains unknown. In retinal rod photoreceptors, a long-lived photois... | 10.1038/nrn2789 | This paper shows that olfactory signalling in mammals does not require high amplification. |
10.1126/science.1106267 | 103,112,140 | We describe two male-specific olfactory receptors (ORs) in the silk moth, Bombyx mori , that are mutually exclusively expressed in a pair of adjacent pheromone-sensitive neurons of male antennae: One is specifically tuned to bombykol, the sex pheromone, and the other to bombykal, its oxidized form. Both pheromone ORs a... | 10.1038/nrn2789 | The first indication that insect chemosensory receptors form functional heteromers. |
10.1146/annurev.cellbio.21.012804.093915 | 27,036,606 | The main olfactory epithelium of the mouse is a mosaic of 2000 populations of olfactory sensory neurons (OSNs). Each population expresses one allele of one of the 1000 intact odorant receptor (OR) genes. An OSN projects a single unbranched axon to a single glomerulus, from an array of 1600–1800 glomeruli in the main ol... | 10.1038/nrn2789 | A critical and comprehensive review on the instructive role of ORs for axonal targeting of the olfactory bulb. |
10.1073/pnas.1213515110 | 122,485,010 | Hepatitis C virus (HCV) replication is dependent on microRNA 122 (miR-122), a liver-specific microRNA that recruits Argonaute 2 to the 5′ end of the viral genome, stabilizing it and slowing its decay both in cell-free reactions and in infected cells. Here we describe the RNA degradation pathways against which miR-122 p... | 10.1038/nrmicro3506 | References 15 and 23 provide the first direct evidence that miR-122, acting in association with AGO2, stabilizes and protects the HCV RNA genome from XRN1-mediated decay. |
10.1128/jvi.00339-11 | 41,423,901 | ABSTRACT Sequences in the 5′ untranslated region (5′UTR) of hepatitis C virus (HCV) RNA is important for modulating both translation and RNA replication. The translation of the HCV genome depends on an internal ribosome entry site (IRES) located within the 341-nucleotide 5′UTR, while RNA replication requires a smaller ... | 10.1038/nrmicro3506 | This paper provides evidence that PCBP2 mediates circularization of the HCV genome through a protein–protein bridge. |
10.1073/pnas.0704894104 | 81,656,878 | Recently identified hepatitis C virus (HCV) isolates that are infectious in cell culture provide a genetic system to evaluate the significance of virus–host interactions for HCV replication. We have completed a systematic RNAi screen wherein siRNAs were designed that target 62 host genes encoding proteins that physical... | 10.1038/nrmicro3506 | This investigation consists of a comprehensive RNAi screen of protein factors suspected of interacting with or otherwise regulating HCV RNA replication. |
10.1126/science.1178178 | 62,449,592 | The liver-expressed microRNA-122 (miR-122) is essential for hepatitis C virus (HCV) RNA accumulation in cultured liver cells, but its potential as a target for antiviral intervention has not been assessed. We found that treatment of chronically infected chimpanzees with a locked nucleic acid (LNA)–modified oligonucleot... | 10.1038/nrmicro3506 | This report details the impact of therapeutic sequestration of miR-122 on HCV replication and the intrahepatic transcriptome in chimpanzees. |
10.1126/science.1113329 | 62,604,554 | MicroRNAs are small RNA molecules that regulate messenger RNA (mRNA) expression. MicroRNA 122 (miR-122) is specifically expressed and highly abundant in the human liver. We show that the sequestration of miR-122 in liver cells results in marked loss of autonomously replicating hepatitis C viral RNAs. A genetic interact... | 10.1038/nrmicro3506 | This paper demonstrates that miR-122 interacts directly with the HCV 5′ UTR and promotes amplification of the genome. |
10.1523/jneurosci.1940-04.2004 | 19,830,400 | Although the basic molecular components that promote regulated neurotransmitter release are well established, the contribution of these proteins as regulators of the plasticity of neurotransmission and refinement of synaptic connectivity during development is elaborated less fully. For example, during the period of syn... | 10.1038/nrn2237 | In this study, the authors use targeted mutagenesis in the mouse to demonstrate the requirement for two SNAP25 isoforms in postnatal development. |
10.1101/gad.1558107 | 123,943,928 | Many metazoan gene transcripts exhibit neuron-specific splicing patterns, but the developmental control of these splicing events is poorly understood. We show that the splicing of a large group of exons is reprogrammed during neuronal development by a switch in expression between two highly similar polypyrimidine tract... | 10.1038/nrn2237 | This study demonstrates that, during differentiation into neurons, cells switch from expressing PTB to nPTB. This switch induces a series of new alternative splicing patterns in the differentiating cells. |
10.1126/science.1118265 | 45,567,022 | The Prader-Willi syndrome is a congenital disease that is caused by the loss of paternal gene expression from a maternally imprinted region on chromosome 15. This region contains a small nucleolar RNA (snoRNA), HBII-52, that exhibits sequence complementarity to the alternatively spliced exon Vb of the serotonin recepto... | 10.1038/nrn2237 | This study was the first to identify a regulatory RNA for alternative splicing. |
10.1146/annurev.biophys.35.040405.101958 | 59,726,316 | Exocytosis is initiated within a highly localized region of contact between two biological membranes. Small areas of these membranes draw close, molecules on the two surfaces interact, and structural transformations take place. Membrane fusion requires the action of proteins specialized for this task, and these protein... | 10.1038/nrn2191 | An excellent review of the issues regarding the mechanism by which the fusion pore is generated. |
10.1152/jn.00258.2004 | 122,371,583 | We have used Monte Carlo simulations to understand the generation of quantal responses at the single active zones of CA1 synapses. We constructed a model of AMPA channel activation that accounts for the responses to controlled glutamate application and a model of glutamate diffusion in the synaptic cleft. With no furth... | 10.1038/nrn2191 | This paper used Monte-Carlo simulations to show how the glutamate released from a vesicle diffuses in the cleft and activates AMPA channels. |
10.1098/rstb.2002.1249 | 38,557,110 | Working on the idea that postsynaptic and presynaptic mechanisms of long-term potentiation (LTP) expression are not inherently mutually exclusive, we have looked for the existence and functionality of presynaptic mechanisms for augmenting transmitter release in hippocampal slices. Specifically, we asked if changes in g... | 10.1038/nrn2191 | A review of experiments pointing to the importance of the mode of vesicle release in AMPA channel activation. Experiments suggesting a role for this process in synaptic plasticity are also reviewed. |
10.1126/science.280.5369.1596 | 38,398,771 | The subunit stoichiometry of several ligand-gated ion channel receptors is still unknown. A counting method was developed to determine the number of subunits in one family of brain glutamate receptors. Successful application of this method in an HEK cell line provides evidence that ionotropic glutamate receptors share ... | 10.1038/nrn2191 | An important paper demonstrating the tetrameric structure of AMPA channels and the fact that different channel occupancy by glutamate leads to different single-channel conductance. |
10.1046/j.1365-2958.2000.02006.x | 103,474,011 | Plasmids are extrachromosomal elements built from a selection of generally quite well understood survival and propagation functions, including replication, partitioning, multimer resolution, post‐segregational killing and conjugative transfer. Evolution has favoured clustering of these modules to form plasmid cores or ... | 10.1038/nrmicro2882 | This review concisely explores the structural traits, as well as the survival and propagation strategies, of plasmids. |
10.1111/j.1365-2958.2004.04366.x | 45,319,483 | Summary The repABC replicons contain an operon encoding the initiator protein (RepC) and partitioning proteins (RepA and RepB). The latter two proteins negatively regulate the transcription of the operon. In this article we have identified two novel regulatory elements, located within the conserved repB–repC intergenic... | 10.1038/nrmicro2882 | A comprehensive study that, together with references 18 and 20, demonstrates the role of antisense regulation in repC expression. |
10.1111/j.1365-2958.2011.07789.x | 60,872,638 | Summary Vegetative replication and partitioning of many plasmids and some chromosomes of alphaproteobacteria are directed by their repABC operons. RepA and RepB proteins direct the partitioning of replicons to daughter cells, while RepC proteins are replication initiators, although they do not resemble any characterize... | 10.1038/nrmicro2882 | The first biochemical study of RepC and its interaction with the putative origin of replication. |
10.1128/mmbr.62.2.434-464.1998 | 123,195,808 | SUMMARY An essential feature of bacterial plasmids is their ability to replicate as autonomous genetic elements in a controlled way within the host. Therefore, they can be used to explore the mechanisms involved in DNA replication and to analyze the different strategies that couple DNA replication to other critical eve... | 10.1038/nrmicro2882 | A comprehensive review of plasmid replication mechanisms and their controls. |
10.1073/pnas.0503458102 | 29,264,041 | The vir genes of Agrobacterium tumefaciens tumor-inducing (Ti) plasmids direct the transfer of oncogenic portion of the Ti (tumor-inducing) plasmid that is transferred to plant cells (T-DNA) into plant cells and are coordinately induced by plant-released phenolic chemical signals. We have used DNA microarrays, represen... | 10.1038/nrmicro2882 | This study, together with references 65 and 32, shows that extracellular signalling cues can increase the copy number of replicons containing repABC systems. |
10.1046/j.1365-2958.2000.02005.x | 122,897,168 | Bacterial plasmids maintain their number of copies by negative regulatory systems that adjust the rate of replication per plasmid copy in response to fluctuations in the copy number. Three general classes of regulatory mechanisms have been studied in depth, namely those that involve directly repeated sequences (iterons... | 10.1038/nrmicro2882 | This review describes the mechanisms that regulate plasmid copy number in response to fluctuations of cis - or trans -acting elements. |
10.1002/glia.22477 | 104,281,662 | Müller cells, the major type of glial cells in the retina, are responsible for the homeostatic and metabolic support of retinal neurons. By mediating transcellular ion, water, and bicarbonate transport, Müller cells control the composition of the extracellular space fluid. Müller cells provide trophic and anti‐oxidativ... | 10.1038/nrn3723 | An excellent review of recently discovered functions of Müller glia. |
10.1073/pnas.1312009110 | 102,183,497 | Significance Retinal injury in zebrafish stimulates Müller glia (MG) to undergo a reprogramming event that transitions their identity from quiescent supportive cells to multipotent progenitors capable of repairing the damaged retina. Understanding the mechanisms underlying this reprogramming event may provide insights ... | 10.1038/nrn3723 | This paper identifies a changing DNA methylation landscape as Müller glia transition to stem cells. |
10.1242/dev.090738 | 39,235,293 | Müller glia function as retinal stem cells in adult zebrafish. In response to loss of retinal neurons, Müller glia partially dedifferentiate, re-express neuroepithelial markers and re-enter the cell cycle. We show that the immunoglobulin superfamily adhesion molecule Alcama is a novel marker of multipotent retinal stem... | 10.1038/nrn3723 | This study demonstrates interkinetic nuclear migration, asymmetrical division and the participation of N-cadherin in the generation of a Müller glial cell-derived progenitor. |
10.1002/cne.21730 | 107,300,555 | Abstract Müller glial cells are the major type of glia in the mammalian retina. To identify the molecular machinery that defines Müller glial cell identity and function, single cell gene expression profiling was performed on Affymetrix microarrays. Identification of a cluster of genes expressed at high levels suggests ... | 10.1038/nrn3723 | An analysis of the mouse Müller glial cell transcriptome at the single cell level suggests some similarity with retinal progenitors and that there may be heterogeneity among Müller glia. |
10.1073/pnas.0402129101 | 123,079,233 | It has long been believed that the retina of mature mammals is incapable of regeneration. In this study, using the N -methyl- d -aspartate neurotoxicity model of adult rat retina, we observed that some Müller glial cells were stimulated to proliferate in response to a toxic injury and produce bipolar cells and rod phot... | 10.1038/nrn3723 | This study identified Müller glia as a source of new neurons in the mammalian retina. |
10.1523/jneurosci.4193-06.2007 | 38,881,954 | Regeneration in the mammalian CNS is severely limited. Unlike in the chick, current models hold that retinal neurons are never regenerated. Previously we demonstrated that, in the adult mammalian retina, Müller glia dedifferentiate and produce retinal cells, including photoreceptors, after acute neurotoxic injury in vi... | 10.1038/nrn3723 | This study indicates that WNT signalling may control the generation of Müller glial cell-derived progenitors in mammals. |
10.1242/dev.091355 | 62,622,355 | Non-mammalian vertebrates have a robust ability to regenerate injured retinal neurons from Müller glia (MG) that activate the gene encoding the proneural factor Achaete-scute homolog 1 (Ascl1; also known as Mash1 in mammals) and de-differentiate into progenitor cells. By contrast, mammalian MG have a limited regenerati... | 10.1038/nrn3723 | This report shows ASCL1 overexpresssion can drive Müller glial cell reprogramming in postnatal mice. Interestingly, this protein also drives Müller glial cell reprogramming in zebrafish (see references 10, 63 and 64). |
10.1073/pnas.1107220108 | 82,931,883 | Key to successful retina regeneration in zebrafish are Müller glia (MG) that respond to retinal injury by dedifferentiating into a cycling population of retinal progenitors. Although recent studies have identified several genes involved in retina regeneration, the signaling mechanisms underlying injury-dependent MG pro... | 10.1038/nrn3723 | This paper shows that Wnt signalling is necessary for retina regeneration in the injured zebrafish retina and that Gsk3β inhibition suffices to drive Müller glial cell reprogramming in the uninjured retina. |
10.1523/jneurosci.3838-12.2013 | 20,238,277 | Intense light exposure causes photoreceptor apoptosis in dark-adapted adult albino zebrafish ( Danio rerio ). Subsequently, Müller glia increase expression of the Achaete-scute complex-like 1a (Ascl1a) and Signal transducer and activator of transcription 3 (Stat3) transcription factors and re-enter the cell cycle to yi... | 10.1038/nrn3723 | This paper suggests Tnfα may initiate the injury response in Müller glia, as it is produced by injured cells and is necessary for stimulating the proliferation of Müller glia. |
10.1002/cne.23213 | 104,189,861 | Abstract We analyzed the role of Stat3, Ascl1a, and Lin28a in Müller glia reentry into the cell cycle following damage to the zebrafish retina. Immunohistochemical analysis was employed to determine the temporal and spatial expression of Stat3 and Ascl1a proteins following rod and cone photoreceptor cell apoptosis. Sta... | 10.1038/nrn3723 | This paper identifies a range of Müller glial cell populations that increase Stat3 expression following retinal injury and suggests multiple roles for Stat3 in the injured retina. |
10.1113/jphysiol.1973.sp010327 | 82,469,831 | 1. The facilitation of neuromuscular transmission, which occurs during repetitive activation, was examined in the proximal accessory flexor muscle in walking legs of the lobster using electrophysiological techniques. 2. Post‐synaptic potentials (p.s.p.s) in different muscle fibres facilitated to markedly different degr... | 10.1038/nrn876 | Introduces the case for a retrograde influence of target cells on synapses, with a clear-cut example from crustacean neuromuscular physiology. |
10.1126/science.7904774 | 21,920,200 | As changes in synaptic strength are thought to be critical for learning and memory, it would be useful to monitor the activity of individual identified synapses on mammalian central neurons. Calcium imaging of cortical neurons grown in primary culture was used to visualize the activation of individual postsynaptic elem... | 10.1038/nrn876 | References 31 and 32 used optical methods to analyse synaptic transmission, and revealed heterogeneous release properties of synapses in tissue culture. |
10.1523/jneurosci.19-19-08419.1999 | 19,247,541 | Synaptic functional differentiation of crayfish phasic and tonic motor neurons is large. For one impulse, quantal release of neurotransmitter is typically 100–1000 times higher for phasic synapses. We tested the hypothesis that differences in synaptic strength are determined by differences in synaptic calcium entry. Ca... | 10.1038/nrn876 | For crustacean synapses, Ca 2+ entry per active zone cannot explain the difference in transmitter release between phasic and tonic synapses. |
10.1523/jneurosci.19-02-00726.1999 | 41,134,335 | We studied how Ca 2+ influx through different subtypes of Ca 2+ channels couples to release at a calyx-type terminal in the rat medial nucleus of the trapezoid body by simultaneously measuring the presynaptic Ca 2+ influx evoked by a single action potential and the EPSC. Application of subtype-specific toxins showed th... | 10.1038/nrn876 | Differential localization of Ca 2+ channel types at active zones can account for their relative effectiveness in releasing transmitter. |
10.1111/j.1469-7793.1997.585ba.x | 67,154,740 | Action potential (AP)‐induced fluorescence transients were measured, using Ca 2+ indicators and a spot‐detection method, at single nerve terminals of a cultured Xenopus neuromuscular junction preparation with simultaneous measurement of neurotransmitter release. Transients obtained using the low affinity Ca 2+ indicato... | 10.1038/nrn876 | Highly resolved observation of Ca 2+ transients at active zones of the amphibian NMJ. |
10.1523/jneurosci.15-12-07940.1995 | 85,600,057 | Augmentation and posttetanic potentiation--two forms of short-term synaptic enhancement produced by repetitive presynaptic action potentials--are dependent on the buildup and decay of nerve terminal residual calcium that occurs on the seconds to minutes time scale. With the goal of providing a quantitative understandin... | 10.1038/nrn876 | Presents the single-compartment model of Ca 2+ signals in individual boutons. |
10.1523/jneurosci.11-06-01496.1991 | 58,973,054 | A number of calcium buffers were examined for their ability to reduce evoked transmitter release when injected into the presynaptic terminal of the squid giant synapse. Injection of EGTA was virtually ineffective at reducing transmitter release, even at estimated intracellular concentrations up to 80 mM. Conversely, th... | 10.1038/nrn876 | The first examination of the effects of introduced Ca 2+ buffers on transmission. 'Slow' buffers were ineffective at the squid giant synapse, whereas 'fast' buffers were effective. |
10.1523/jneurosci.20-04-01374.2000 | 124,392,723 | Synapses display remarkable alterations in strength during repetitive use. Different types of synapses exhibit distinctive synaptic plasticity, but the factors giving rise to such diversity are not fully understood. To provide the experimental basis for a general model of short-term plasticity, we studied three synapse... | 10.1038/nrn876 | Descriptions of case I and case II synaptic differentiation are presented in references 157–159 for both crustacean and mammalian CNS synaptic connections. |
10.1002/cne.903510313 | 60,116,853 | Abstract The specific inhibitory motoneuron to the crayfish (Procambarus clarkii) opener muscle provides neuromuscular synapses to the muscle fibers and axoaxonal synapses to the excitatory motor nerve terminals. Freeze fracture of the membrane in both types of synapses show that the presynaptic active zone consists of... | 10.1038/nrn876 | Non-uniform separation of Ca 2+ channels and docked vesicles is illustrated in the freeze-fracture studies of crustacean synapses described in references 161 and 163 |
10.1073/pnas.96.24.14043 | 62,077,663 | Plague, one of the most devastating diseases of human history, is caused by Yersinia pestis . In this study, we analyzed the population genetic structure of Y. pestis and the two other pathogenic Yersinia species, Y. pseudotuberculosis and Y. enterocolitica . Fragments of five housekeeping genes and a gene involved in ... | 10.1038/nrmicro730 | Use of molecular clock (MLST) analysis to show that Y. pestis evolved from Y. pseudotuberculosis between the last 1,500 and 20,000 years. |
10.1126/science.1069972 | 104,325,146 | Transmission by flea bite is a relatively recent adaptation that distinguishes Yersinia pestis , the plague bacillus, from closely related enteric bacteria. Here, a plasmid-encoded phospholipase D (PLD), previously characterized as Yersinia murine toxin (Ymt), was shown to be required for survival of Y. pestis in the m... | 10.1038/nrmicro730 | Shows a clear role for the so called 'murine toxin' on the acquired plasmid pMT1 as a phospholipase that is important for the survival of Y. pestis in the flea midgut. |
10.1073/pnas.94.10.5395 | 38,578,223 | Local translation of proteins in distal dendrites is thought to support synaptic structural plasticity. We have previously shown that metabotropic glutamate receptor (mGluR1) stimulation initiates a phosphorylation cascade, triggering rapid association of some mRNAs with translation machinery near synapses, and leading... | 10.1038/nrn1667 | Initial description of neurotransmitter activation of FMRP synthesis at the synapse (see also reference 25). |
10.1523/jneurosci.0099-04.2004 | 80,183,823 | Fragile X syndrome is caused by the absence of the mRNA-binding protein Fragile X mental retardation protein (FMRP), which may play a role in activity-regulated localization and translation of mRNA in dendrites and at synapses. We investigated whether neuronal activity and glutamatergic signals regulate trafficking of ... | 10.1038/nrn1667 | Shows clearly, for the first time, evidence of activity-dependent regulation of FMRP and FMR1 mRNA trafficking in dendrites and synapses. In particular, the authors show that synaptic activation through the mGluR5 receptor regulates the localization of FMRP and FMR1 mRNA in dendrites. |
10.1073/pnas.151231598 | 81,666,835 | The absence of the fragile X mental retardation protein (FMRP), encoded by the FMR1 gene, is responsible for pathologic manifestations in the Fragile X Syndrome, the most frequent cause of inherited mental retardation. FMRP is an RNA-binding protein associated with polysomes as part of a messenger ribonucleoprotein (mR... | 10.1038/nrn1667 | The authors characterized two cytoplasmic FMRP-interacting proteins, both of which are also present at synapses.This work represents one of the first links between FMRP and the cytoskeleton (see also reference 68). |
10.1101/gad.1025202 | 41,626,470 | RNA interference (RNAi) is a flexible gene silencing mechanism that responds to double-stranded RNA by suppressing homologous genes. Here, we report the characterization of RNAi effector complexes (RISCs) that contain small interfering RNAs and microRNAs (miRNAs). We identify two putative RNA-binding proteins, the Dros... | 10.1038/nrn1667 | This study provides the first evidence that the D. melanogaster FMRP is part of the RNAi-related machinery (see also reference 88). |
10.1101/gad.1022002 | 125,244,144 | Fragile X syndrome is a common form of inherited mental retardation caused by the loss of FMR1 expression. The FMR1 gene encodes an RNA-binding protein that associates with translating ribosomes and acts as a negative translational regulator. In Drosophila , the fly homolog of the FMR1 protein (dFMR1) binds to and repr... | 10.1038/nrn1667 | The authors of this study suggest a model in which the RNAi pathway and D. melanogaster FMRP-mediated translational control intersect with each other (see also reference 86). |
10.1101/gad.2055511 | 99,061,410 | Histone H3 variant H3.3, while differing from canonical H3 (H3.1) by only five amino acids, is assembled into nucleosomes, along with histone H4, at genic regions by the histone chaperone HIRA, whereas H3.1 is assembled into nucleosomes in a CAF-1-dependent reaction. Here, we show that phosphorylation of histone H4 Ser... | 10.1038/nsmb.2461 | Shows that phosphorylation of histone H4 Ser47 by Pak2 differentially regulates H3.1–H4 and H3.3–H4 deposition by promoting the association of HIRA with H3.3–H4 and inhibiting the association of CAF-1 with H3.1–H4 |
10.1523/jneurosci.2621-05.2005 | 38,228,097 | Recent reports of a high response to bodies in the fusiform face area (FFA) challenge the idea that the FFA is exclusively selective for face stimuli. We examined this claim by conducting a functional magnetic resonance imaging experiment at both standard (3.125 × 3.125 × 4.0 mm) and high resolution (1.4 × 1.4 × 2.0 mm... | 10.1038/nrn2314 | This study demonstrated the power of high-resolution fMRI to dissociate the selectivity of two adjacent functional regions (one face-selective, the other body-selective) that are lumped together as one larger region with less clear selectivity by standard-resolution fMRI. |
10.1146/annurev.neuro.27.070203.144220 | 4,589,739 | ▪ Abstract The discovery and analysis of cortical visual areas is a major accomplishment of visual neuroscience. In the past decade the use of noninvasive functional imaging, particularly functional magnetic resonance imaging (fMRI), has dramatically increased our detailed knowledge of the functional organization of th... | 10.1038/nrn2314 | This paper provides a detailed review of what fMRI has taught us about the organization of the object-vision pathway in the human cortex. |
10.1126/science.1063736 | 82,868,626 | The functional architecture of the object vision pathway in the human brain was investigated using functional magnetic resonance imaging to measure patterns of response in ventral temporal cortex while subjects viewed faces, cats, five categories of man-made objects, and nonsense pictures. A distinct pattern of respons... | 10.1038/nrn2314 | This seminal paper introduced the basic thinking behind the now widely used multi-voxel pattern analyses. |
10.1126/science.1119983 | 82,004,581 | Face perception is a skill crucial to primates. In both humans and macaque monkeys, functional magnetic resonance imaging (fMRI) reveals a system of cortical regions that show increased blood flow when the subject views images of faces, compared with images of objects. However, the stimulus selectivity of single neuron... | 10.1038/nrn2314 | This study gave the first demonstration that a strong clustering of face-selective neurons underlies the strongly face-selective regions found with fMRI in both humans and monkeys. |
10.1098/rstb.2005.1623 | 104,056,516 | This year, the field of neuroscience celebrates the 50th anniversary of Mountcastle's discovery of the cortical column. In this review, we summarize half a century of research and come to the disappointing realization that the column may have no function. Originally, it was described as a discrete structure, spanning t... | 10.1038/nrn2314 | This extensive review of decades of studies on cortical columns reaches the challenging conclusion that, despite the great amount of work that has been carried out, there is no clear evidence that a columnar structure serves any purpose. |
10.1523/jneurosci.2481-06.2006 | 103,216,410 | Visual object recognition relies critically on learning. However, little is known about the effect of object learning in human visual cortex, and in particular how the spatial distribution of training effects relates to the distribution of object and face selectivity across the cortex before training. We scanned human ... | 10.1038/nrn2314 | This paper demonstrated that object-discrimination training alters the pattern of activity for trained objects across the extrastriate cortex in a way that is not predicted by either the pattern of activity before training or the distribution of face selectivity. |
10.1002/per.629 | 17,803,871 | Genetic influences on personality differences are ubiquitous, but their nature is not well understood. A theoretical framework might help, and can be provided by evolutionary genetics. We assess three evolutionary genetic mechanisms that could explain genetic variance in personality differences: selective neutrality, m... | 10.1038/nrn2793 | A theoretical argument that intergenerationally accumulated rare variants (mutation load) underlie much of the genetic variance in intelligence. |
10.1126/science.1167371 | 125,305,857 | Little is known about the genetic contribution to individual differences in neural networks subserving cognition function. In this functional magnetic resonance imaging (fMRI) twin study, we found a significant genetic influence on brain activation in neural networks supporting digit working memory tasks. Participants ... | 10.1038/nrn2793 | An empirical demonstration of heritable individual differences in fMRI activation patterns underlying distinct cognitive strategies to solve a working memory task in remembering exposure to digits. |
10.1523/jneurosci.1413-09.2009 | 20,556,996 | Here, we map a quantitative trait locus (QTL) with a large effect on predisposition to barbiturate (pentobarbital) withdrawal to a 0.44 Mb interval of mouse chromosome 1 syntenic with human 1q23.2. We report a detailed analysis of the genes within this interval and show that it contains 15 known and predicted genes, 12... | 10.1038/nrn2834 | This paper documents a search for genes in a quantitative trait locus associated with withdrawal. Mice containing a knockout of one these genes, Girk3 , exhibit less severe withdrawal from sedatives. |
10.1159/000227772 | 64,311,516 | Many neurotransmitters activate G-protein-gated inwardly rectifying K<sup>+</sup> (Kir3) channels by stimulating G-protein-coupled receptors. However, in native systems, only receptors coupled to pertussis-toxin (PTX)-sensitive G proteins (Gi/Go) have been shown to be able to activate Kir3 channels through ... | 10.1038/nrn2834 | This study and references 84 and 85 show that PTX-sensitive Gα subunits alter GIRK function by interacting directly with the channel. |
10.1523/jneurosci.3251-06.2007 | 19,248,799 | Two determinants of dopamine release from terminals in striatal and limbic structures are the pattern and rate of dopamine neuron firing in the ventral midbrain. This activity is regulated in part by somatodendritic release of dopamine and subsequent feedback inhibition through activation of D 2 receptors on dopamine n... | 10.1038/nrn2834 | This study reports that the dopamine-dependent slow IPSC is persistently reduced after strong dendrodendritic release of dopamine. |
10.1073/pnas.0811685106 | 82,767,452 | Excitatory synapses in the brain undergo activity-dependent changes in the strength of synaptic transmission. Such synaptic plasticity as exemplified by long-term potentiation (LTP) is considered a cellular correlate of learning and memory. The presence of G protein-activated inwardly rectifying K + (GIRK) channels nea... | 10.1038/nrn2834 | This paper provides evidence that adenosine-dependent reversal of glutamatergic LTP (depotentiation) involves activation of GIRK channels. |
10.1523/jneurosci.4899-04.2005 | 19,249,026 | Opioids can evoke analgesia by inhibiting neuronal targets in either the brain or spinal cord, and multiple presynaptic and postsynaptic inhibitory mechanisms have been implicated. The relative significance of presynaptic and postsynaptic inhibition to opioid analgesia is essentially unknown, as are the identities and ... | 10.1038/nrn2834 | This study and references 135, 137 and 138 implicate GIRK channels in the analgesic effects of opioids. |
10.1073/pnas.94.3.923 | 81,720,513 | G protein-gated, inwardly rectifying K + channels (GIRK) are effectors of G protein-coupled receptors for neurotransmitters and hormones and may play an important role in the regulation of neuronal excitability. GIRK channels may be important in neurodevelopment, as suggested by the recent finding that a point mutation... | 10.1038/nrn2834 | This study is the first to use the GIRK-knockout mouse and shows that the loss of GIRK channels leads to spontaneous convulsions and a propensity for generalized seizures. |
10.1523/jneurosci.2699-07.2008 | 82,443,875 | The pan neurotrophin receptor p75 NTR signals programmed cell death both during nervous system development and after neural trauma and disease in the adult. However, the molecular pathways by which death is mediated remain poorly understood. Here, we show that this cell death is initiated by activation of G-protein-cou... | 10.1038/nrn2834 | This paper reports that activation of the nerve growth factor receptor leads to enhanced GIRK channel activity and generates a sustained K + efflux that triggers apoptosis in dorsal root ganglion neurons. |
10.1126/science.186.4169.1126 | 79,748,875 | Golgi studies reveal abnormally long, thin spines and the absence of short, thick spines on dendrites of cortical neurons in retarded children with normal karyotypes. The degree of dendritic spine loss and abnormality appears to be related to age and the severity of developmental retardation. Dendritic spine "dysgenesi... | 10.1038/nrn.2018.16 | This seminal study observes the presence of microstructural pathology in the brains of individuals with intellectual disability. |
10.1152/jn.1998.80.2.832 | 121,927,057 | Kobayashi, Yasushi, Kenji Kawano, Aya Takemura, Yuka Inoue, Toshihiro Kitama, Hiroaki Gomi, and Mitsuo Kawato. Temporal firing patterns of Purkinje cells in cerebellar ventral paraflocculus during ocular following responses in monkeys. II. Complex spikes. J. Neurophysiol. 80: 832–848, 1998. Many theories of cerebellar ... | 10.1038/nrn1646 | A single-unit study in awake monkeys of climbing fibre and simple spike activity in the ventral paraflocculus during ocular following responses. Results indicate that climbing fibre signals have properties that are transitional between sensory and motor information. |
10.1152/physrev.2001.81.2.539 | 81,537,900 | This review explores how proprioceptive sensory information is organized at spinal cord levels as it relates to a sense of body position and movement. The topic is considered in an historical context and develops a different framework that may be more in tune with current views of sensorimotor processing in other centr... | 10.1038/nrn1646 | A review article that summarizes this group's important studies on the dorsal spinocerebellar tract (DSCT) system in the cat. A key conclusion is that mossy fibre inputs to the cerebellum conveyed by the DSCT system seem to encode whole-hindlimb kinematics. |
10.1046/j.0953-816x.2001.01499.x | 65,296,170 | Abstract In cats decerebrated at the intercollicular level, the cutaneous parallel fibre receptive fields of Purkinje cells, molecular layer interneurons and Golgi cells in the cerebellar C3 zone were delineated by natural stimulation of the skin during extracellular unitary recordings. The locations of these receptive... | 10.1038/nrn1646 | A single-unit mapping study in decerebrate cats showing that skin receptive fields of climbing fibres and local interneurons in individual microzones are similar, whereas the parallel fibre receptive fields of the same Purkinje cells are different. An important conclusion is that excitatory input to Purkinje cells depe... |
10.1152/jn.2000.84.4.1988 | 123,268,403 | We previously showed that inactivating the anterior interpositus nucleus in cats disrupts prehension; paw paths, normally straight and accurate, become curved, hypometric, and more variable. In the present study, we determined the joint kinematic and dynamic origins of this impairment. Animals were restrained in a hamm... | 10.1038/nrn1646 | Reversible lesions with muscimol of the NIA in awake cats showed that the cerebellar paravermal system is important in the anticipatory control of interactions between different limb segments involved in a reaching task. |
10.1126/science.287.5451.248 | 38,447,845 | The memory consolidation hypothesis proposed 100 years ago by Müller and Pilzecker continues to guide memory research. The hypothesis that new memories consolidate slowly over time has stimulated studies revealing the hormonal and neural influences regulating memory consolidation, as well as molecular and cellular mec... | 10.1038/nrn.2016.155 | This comprehensive review of memory consolidation research focuses on the role of the amygdala and of the noradrenergic system in the basolateral amygdala in modulating long-term memory consolidation in other brain regions. |
10.1073/pnas.0601874103 | 38,817,112 | Considerable evidence indicates that glucocorticoid hormones enhance the consolidation of long-term memories for emotionally arousing experiences but not that for less arousing or neutral information. However, previous studies have not determined the basis of such arousal-induced selectivity. Here we report the finding... | 10.1038/nrn.2016.155 | This study shows that glucocorticoids require emotional arousal-induced noradrenergic activation in the basolateral amygdalato influence memory consolidation. |
10.1073/pnas.0900835106 | 102,712,175 | Extensive evidence indicates that the basolateral complex of the amygdala (BLA) modulates the consolidation of memories for emotionally arousing experiences, an effect that involves the activation of the glucocorticoid system. Because the BLA expresses high densities of cannabinoid CB1 receptors, the present experiment... | 10.1038/nrn.2016.155 | This article shows that activation of cannabinoid type 1 receptorsin the basolateral amygdalaenhances memory consolidation and provides the first in vivo demonstration in mammals that endocannabinoid activity is required to enable the memory-enhancing effects of glucocorticoids. |
10.1101/lm.435807 | 59,458,619 | Animal studies provided evidence that stress modulates multiple memory systems, favoring caudate nucleus-based “habit” memory over hippocampus-based “cognitive” memory. However, effects of stress on learning strategy and memory consolidation were not differentiated. We specifically address the effects of psychosocial s... | 10.1038/nrn.2016.155 | This study showed for the first time in humans that stress may promote simple S–R learning at the expense of cognitively more-demanding spatial learning. |
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