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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10.1523/jneurosci.1711-05.2005 | 26,744,036 | Although the induction of persistent behavioral alterations by drugs of abuse requires the regulation of gene transcription, the precise intracellular signaling pathways that are involved remain mainly unknown. Extracellular signal-regulated kinase (ERK) is critical for the expression of immediate-early genes in the st... | 10.1038/nrn2132 | Explores the signal transduction cascades, and their effect on downstream chromatin remodelling and associated gene expression, in striatal neurons in response to cocaine. It shows that cocaine causes induction of H4 acetylation, H3 phosphorylation and CREB phosphorylation through MSK1. |
10.1111/j.1471-4159.2004.02569.x | 82,762,279 | Abstract Antipsychotic drugs regulate gene transcription in striatal neurons by blocking dopamine D 2 ‐like receptors. Little is known about the underlying changes in chromatin structure, including covalent modifications at histone N‐terminal tails that are epigenetic regulators of gene expression. We show that treatme... | 10.1038/nrn2132 | Demonstrates that acute administration of antipsychotic drugs to rodents increases global levels of histone acetylation in the striatum and provides evidence for the signal transduction mechanisms that mediate this effect. |
10.1523/jneurosci.0589-04.2004 | 42,505,391 | The mechanism of action of electroconvulsive seizures (ECS), one of the most effective treatments of major depression, may involve the regulation of gene expression. Chromatin remodeling at gene promoter regions is increasingly recognized as a key control point of gene expression and may, therefore, partly mediate acut... | 10.1038/nrn2132 | Outlines a standardized approach to performing chromatin immunoprecipitation assays in rodent brain tissue. It also provides a detailed analysis of several transient and lasting changes in histone modifications after acute and chronic seizure, in correlation with changes in gene expression at the specific gene promoter... |
10.1126/science.1120972 | 82,369,498 | Mice experiencing repeated aggression develop a long-lasting aversion to social contact, which can be normalized by chronic, but not acute, administration of antidepressant. Using viral-mediated, mesolimbic dopamine pathway–specific knockdown of brain-derived neurotrophic factor (BDNF), we showed that BDNF is required ... | 10.1038/nrn2132 | The authors use chronic social defeat stress as an animal model of depression and demonstrate a crucial role for the neurotrophic factor BDNF in the mesolimbic dopamine pathway in mediating some of the deleterious molecular and behavioural sequelae of this stress paradigm. |
10.1073/pnas.0509735102 | 80,727,546 | Remodeling chromatin is essential for cAMP-regulated gene expression, necessary not only for development but also for memory storage and other enduring mental states. Histone acetylation and deacetylation mediate long-lasting forms of synaptic plasticity in Aplysia as well as cognition in mice. Here, we show that histo... | 10.1038/nrn2132 | Characterizes the influence of chromatin remodelling on cocaine action in the brain. In particular, it shows that recruitment of CBP to the FosB promoter and the resulting H4 acetylation are essential for normal levels of FosB expression, for accumulation of the transcription factor ΔFOSB, and for normal sensitivity to... |
10.1126/science.1138389 | 41,682,339 | Rett syndrome is an autism spectrum disorder caused by mosaic expression of mutant copies of the X-linked MECP2 gene in neurons. However, neurons do not die, which suggests that this is not a neurodegenerative disorder. An important question for future therapeutic approaches to this and related disorders concerns pheno... | 10.1038/nrn2132 | Shows that Rett-like symptoms induced in mice as a result of loss of function mutations in MeCP2 can be largely reversed upon correction of the MeCP2 deficit. This supports the notion that it may be possible to treat Rett syndrome in humans even after it has become symptomatic. |
10.1073/pnas.0505394102 | 79,418,608 | Reduction of prefrontal cortex glutamic acid decarboxylase (GAD 67 ) and reelin (mRNAs and proteins) expression is the most consistent finding reported by several studies of postmortem schizophrenia (SZ) brains. Converging evidence suggests that the reduced GAD 67 and reelin expression in cortical GABAergic interneuron... | 10.1038/nrn2132 | Provides evidence to support their hypothesis that epigenetic abnormalities, specifically, altered methylation of the reelin and Gad67 gene promoters, contribute to the pathophysiology of schizophrenia in a mouse model. |
10.1126/science.1124147 | 107,158,894 | The mammalian Target of Rapamycin (mTOR) protein is a serine-threonine kinase that regulates cell-cycle progression and growth by sensing changes in energy status. We demonstrated that mTOR signaling plays a role in the brain mechanisms that respond to nutrient availability, regulating energy balance. In the rat, mTOR ... | 10.1038/nrn3409 | An early demonstration that mTOR is a fuel sensor within the hypothalamus and regulates energy balance. |
10.1126/science.1072327 | 123,882,297 | D-fenfluramine (d-FEN) was once widely prescribed and was among the most effective weight loss drugs, but was withdrawn from clinical use because of reports of cardiac complications in a subset of patients. Discerning the neurobiology underlying the anorexic action of d-FEN may facilitate the development of new drugs t... | 10.1038/nrn3409 | A seminal paper that demonstrated that the melanocortin neurocircuitry interacts with the 5-HT system to modulate energy balance. |
10.1126/science.1130164 | 104,090,091 | Small noncoding RNAs regulate processes essential for cell growth and development, including mRNA degradation, translational repression, and transcriptional gene silencing (TGS). During a search for candidate mammalian factors for TGS, we purified a complex that contains small RNAs and Riwi, the rat homolog to human Pi... | 10.1038/s41467-017-01049-7 | Results in Referenes 31-34 independently demonstrate the existence of piRNAs as a new class of small RNAs with regulatory potential in the rodent germline. |
10.1126/science.1136567 | 122,819,559 | IKKϵ is an IKK (inhibitor of nuclear factor κBkinase)–related kinase implicated in virus induction of interferon-β (IFNβ). We report that, although mice lacking IKKϵ produce normal amounts of IFNβ, they are hypersusceptible to viral infection because of a defect in the IFN signaling pathway. Specifically, a subset of t... | 10.1038/nrmicro2950 | This work identifies a novel phosphorylation event by IKKɛ on serine 708 of STAT1. |
10.1073/pnas.172195399 | 106,595,815 | A mouse model has been established to investigate the genetic determinism of host susceptibility to West Nile (WN) virus, a member of the genus flavivirus and family Flaviviridae . Whereas WN virus causes encephalitis and death in most laboratory inbred mouse strains after peripheral inoculation, most strains derived f... | 10.1038/nrmicro2950 | This report identifies the mutated flavivirus resistance gene that is present in all inbred mice and allows for a viable WNV mouse model. |
10.1146/annurev.physiol.63.1.647 | 62,614,501 | ▪ Abstract In mammals, a master circadian “clock” resides in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. The SCN clock is composed of multiple, single-cell circadian oscillators, which, when synchronized, generate coordinated circadian outputs that regulate overt rhythms. Eight clock genes have been ... | 10.1038/nrn895 | An excellent review of mammalian circadian biology at the level of the SCN's intranuclear genetic and intracellular biology, and of the output of the SCN to cells of the anterior hypothalamus and peripheral oscillators. |
10.1126/science.284.5423.2177 | 83,414,551 | Regulation of circadian period in humans was thought to differ from that of other species, with the period of the activity rhythm reported to range from 13 to 65 hours (median 25.2 hours) and the period of the body temperature rhythm reported to average 25 hours in adulthood, and to shorten with age. However, those obs... | 10.1038/nrn895 | An important paper that used a forced-desynchrony protocol to show that the endogenous human circadian period is closer to exactly 24 h than was previously believed. |
10.1126/science.2305266 | 100,648,768 | The pacemaker role of the suprachiasmatic nucleus in a mammalian circadian system was tested by neural transplantation by using a mutant strain of hamster that shows a short circadian period. Small neural grafts from the suprachiasmatic region restored circadian rhythms to arrhythmic animals whose own nucleus had been ... | 10.1038/nrn895 | This transplantation study definitively showed that the SCN of the anterior hypothalamus contains the mammalian circadian pacemaker. |
10.1126/science.288.5465.483 | 62,270,073 | The tau mutation is a semidominant autosomal allele that dramatically shortens period length of circadian rhythms in Syrian hamsters. We report the molecular identification of the tau locus using genetically directed representational difference analysis to define a region of conserved synteny in hamsters with both the ... | 10.1038/nrn895 | This study established that the tau locus encodes the protein casein kinase 1ɛ, which is the homologue of the Drosophila gene double-time ; its function in the mammalian circadian clock is to phosphorylate the protein products of Per genes. |
10.1126/science.274.5290.1211 | 19,136,857 | Several transcription factors are expressed at higher levels in the waking than in the sleeping brain. In experiments with rats, the locus coeruleus, a noradrenergic nucleus with diffuse projections, was found to regulate such expression. In brain regions depleted of noradrenergic innervation, amounts of c-Fos and nerv... | 10.1038/nrn895 | A pioneering study of state-dependent gene expression that describes the dependency of such expression during waking on a state-dependent neuromodulatory system — that of noradrenaline, which is itself associated with waking. |
10.1126/science.1094539 | 20,216,031 | During the sleep cycle in cats, neurons localized to the posterolateral pole of the nucleus locus coeruleus and the nucleus subcoeruleus undergo discharge rate changes that are the opposite of those of the pontine reticular giant cells. The inverse rate ratios and activity curves of these two interconnected populations... | 10.1038/nrn895 | A presentation of the reciprocal-interaction model of sleep-state control, in which the regular alternation of REM and NREM results from an interaction in the mesopontine brainstem between aminergic REM-on and cholinergic REM-off cell populations (see also reference 45 |
10.1126/science.271.5246.216 | 123,170,299 | The rostral hypothalamus and adjacent basal forebrain participate in the generation of sleep, but the neuronal circuitry involved in this process remains poorly characterized. Immunocytochemistry was used to identify the FOS protein, an immediate-early gene product, in a group of ventrolateral preoptic neurons that is ... | 10.1038/nrn895 | A landmark study of sleep–wake control by the hypothalamus, showing projection from the sleep-promoting VLPO of the anterior hypothalamus to the wake-promoting TMN of the posterior hypothalamus, with corresponding sleep-dependent activation of the VLPO. |
10.1126/science.276.5316.1265 | 38,274,811 | Both subjective and electroencephalographic arousal diminish as a function of the duration of prior wakefulness. Data reported here suggest that the major criteria for a neural sleep factor mediating the somnogenic effects of prolonged wakefulness are satisfied by adenosine, a neuromodulator whose extracellular concent... | 10.1038/nrn895 | One of the first studies to indicate a role for adenosine as the endogenous somnogen whose build-up during waking leads to homeostatic sleep pressure (see also reference 117 |
10.1126/science.1067262 | 104,374,991 | Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker—the suprachiasmatic nucleus (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor cones, the only known retinal photoreceptors. Here, we show that retinal ganglion cells i... | 10.1038/nrn895 | A demonstration that it is a subset of the RGCs themselves that transduce photic input into a circadian signal to the SCN through the RHT. |
10.1126/science.1470919 | 20,870,598 | Arachidonylethanolamide, an arachidonic acid derivative in porcine brain, was identified in a screen for endogenous ligands for the cannabinoid receptor. The structure of this compound, which has been named "anandamide," was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed b... | 10.1038/nrn1247 | This paper outlines the ground-breaking isolation of anandamide from pig brain and the ability of this lipid derivative to activate cannabinoid receptors. |
10.1073/pnas.96.21.12198 | 121,956,023 | Synthetic cannabinoids produce behavioral analgesia and suppress pain neurotransmission, raising the possibility that endogenous cannabinoids serve naturally to modulate pain. Here, the development of a sensitive method for measuring cannabinoids by atmospheric pressure-chemical ionization mass spectrometry permitted m... | 10.1038/nrn1247 | By showing that anandamide is produced in and released from brain neurons under physiological conditions, references 14–16 established the role of this compound as an endogenous ligand for cannabinoid receptors. |
10.1126/science.277.5329.1094 | 84,360,108 | Anandamide, an endogenous ligand for central cannabinoid receptors, is released from neurons on depolarization and rapidly inactivated. Anandamide inactivation is not completely understood, but it may occur by transport into cells or by enzymatic hydrolysis. The compound N -(4-hydroxyphenyl)arachidonylamide (AM404) was... | 10.1038/nrn1247 | Together with reference 50, this paper identifies facilitated transport as the first step in anandamide deactivation and introduces the first anandamide transport inhibitor, AM404. |
10.1126/science.290.5489.150 | 83,124,376 | Memapsin 2 (β-secretase) is a membrane-associated aspartic protease involved in the production of β-amyloid peptide in Alzheimer's disease and is a major target for drug design. We determined the crystal structure of the protease domain of human memapsin 2 complexed to an eight-residue inhibitor at 1.9 angstrom resolut... | 10.1038/nrn1495 | Crystal structure of β-secretase, which was crucial for rational inhibitor design. |
10.1113/jphysiol.1979.sp012969 | 100,697,218 | 1. Propagation of action potentials at high frequency was studied in a branching axon of the lobster by means of simultaneous intracellular recording both before and after the branch point. 2. Although the branching axon studied has a geometrical ratio close to one (perfect impedance matching) conduction across the bra... | 10.1038/nrn1397 | Demonstration and analysis of differential propagation block at the branch point of a lobster peripheral axon. |
10.1073/pnas.95.14.8345 | 60,348,095 | A rapid, reversible enhancement of synaptic transmission from a sensory neuron is reported and explained by impulses that reverse direction, or reflect, at axon branch points. In leech mechanosensory neurons, where one can detect reflection because it is possible simultaneously to study electrical activity in separate ... | 10.1038/nrn1397 | Experimental evidence that action potential propagation might reflect at branch points of invertebrate axons. Reflected action potentials facilitates synaptic transmission. |
10.1152/jn.00057.2002 | 40,315,813 | The mitral cell primary dendrite plays an important role in transmitting distal olfactory nerve input from olfactory glomerulus to the soma-axon initial segment. To understand how dendritic active properties are involved in this transmission, we have combined dual soma and dendritic patch recordings with computational ... | 10.1038/nrn1397 | First experimental evidence for reflection of action potential propagation in an axon-like dendrite of mammalian neuron. |
10.1073/pnas.0902963106 | 2,682,101 | In 1999, the population of Vancouver Island, Canada, began to experience an outbreak of a fatal fungal disease caused by a highly virulent lineage of Cryptococcus gattii . This organism has recently spread to the Canadian mainland and Pacific Northwest, but the molecular cause of the outbreak remains unknown. Here we s... | 10.1038/nrmicro2522 | This paper demonstrates that isolates from the British Columbia outbreak have an increased capacity to proliferate in macrophages, and show an altered mitochondrial morphology after phagocytosis. These results suggest that intracellular parasitic capability is an important component of the outbreak. |
10.1242/dev.111.4.895 | 26,904,989 | We used retrovirus-mediated gene transfer to study the lineage of neural crest cells in chick embryos. Individual crest cells were infected before they migrated from the neural tube, and their clonal progeny were subsequently revealed in sensory ganglia and associated structures by a histochemical stain for the viral g... | 10.1038/nrn2057 | The only in vivo clonal analysis of the fate of NCCs, showing the two main waves of sensory neurogenesis in the DRG and their respective progenies. |
10.1242/dev.01553 | 40,679,938 | The neural crest is a migratory population of cells that produces many diverse structures within the embryo. Trunk neural crest cells give rise to such structures as the dorsal root ganglia (DRG) and sympathetic ganglia (SG),which form in a metameric pattern along the anterior-posterior axis of the embryo. While static... | 10.1038/nrn2057 | A beautiful live-recording study, imaging for the first time the migration and complex dynamics interaction of NCCs. |
10.1126/science.1091611 | 29,232,759 | Wnt signaling has recently emerged as a key factor in controlling stem cell expansion. In contrast, we show here that Wnt/β-catenin signal activation in emigrating neural crest stem cells (NCSCs) has little effect on the population size and instead regulates fate decisions. Sustained β-catenin activity in neural crest ... | 10.1038/nrn2057 | Demonstration, using mouse genetics, of the importance of WNT signalling for the generation of NCCs. |
10.1083/jcb.84.2.404 | 104,155,191 | The pathway by which semliki forest virus (SFV), a membrane-containing animal virus, enters BHK-21 cells was studied morphologically and biochemically. After attaching to the cell surface, the majority of viruses was rapidly trapped into coated pits, internalized by endocytosis in coated vesicles, and sequestered into ... | 10.1038/nsmb.1456 | One of several papers in which Helenius, Simons and their co-workers showed that the acidic pH of an endosome is a trigger for viral fusion. The demonstration that viruses have evolved to 'sense' the local proton concentration was a contribution both to our knowledge of viral entry mechanisms and to our understanding o... |
10.1073/pnas.79.4.968 | 19,012,519 | A conformational change in the hemagglutinin glycoprotein of influenza virus has been observed to occur to pH values corresponding to those optimal for the membrane fusion activity of the virus. CD, electron microscopic, and sedimentation analyses show that, in the pH range 5.2-4.9, bromelain-solubilized hemagglutinin ... | 10.1038/nsmb.1456 | The discovery that proton binding (low pH) triggers a profound conformational change in influenza virus hemagglutinin. The authors were able to infer the essential characteristics (although not yet the extent) of the conformational change in hemagglutinin, by insightful use of selective proteolysis and by thoughtful in... |
10.1126/science.148.3676.1485 | 21,861,509 | In two different experiments, subjects reported on the visual direction of a flash presented during a voluntary saccade relative to the visual direction of a stimulus viewed prior to the saccade. Under the conditions of the first experiment the report given by the subject was primarily determined by the relative retina... | 10.1038/nrn750 | Although not the first one on this topic, this is the most influential paper to have drawn attention to mislocalization near the time of saccades. |
10.1126/science.7063881 | 63,189,930 | In darkness, observers partially paralyzed with curare make large (> 20 degrees) gaze- and dosage-dependent errors in visually localizing eye-level-horizontal and median planes, in matching the location of a sound to a light, and in pointing at a light. In illuminated, structured visual fields visual localization an... | 10.1038/nrn750 | Probably the most elegant demonstration of the role of the internal EPS in stimulus localization and of its overriding by ambient visual cues. |
10.1128/jvi.01174-13 | 67,543,170 | ABSTRACT Highly divergent vaccine-derived polioviruses (VDPVs) have been isolated from sewage in Tallinn, Estonia, since 2002. Sequence analysis of VDPVs of serotypes 2 and 3 showed that they shared common noncapsid region recombination sites, indicating origination from a single trivalent oral polio vaccine dose, esti... | 10.1038/nrmicro906 | A thorough review of outbreaks caused by circulating vaccine-derived polioviruses. |
10.1128/mcb.00815-07 | 80,984,007 | ABSTRACT SorLA/LR11 (250 kDa) is the largest and most composite member of the Vps10p-domain receptors, a family of type 1 proteins preferentially expressed in neuronal tissue. SorLA binds several ligands, including neurotensin, platelet-derived growth factor-bb, and lipoprotein lipase, and via complex-formation with th... | 10.1038/nrn2516 | Demonstrated Golgi-to-endosome sorting by SORLA and SORLA downregulation in response to retromer (SNX1 and VPS35) knock down. |
10.1242/jcs.009654 | 102,251,006 | The cation-independent mannose 6-phosphate receptor (CIMPR) cycles between the trans-Golgi network (TGN) and endosomes to mediate sorting of lysosomal hydrolases. The endosome-to-TGN retrieval of the CIMPR requires the retromer complex. Genetic, biochemical and structural data support the hypothesis that the retromer c... | 10.1038/nrn2516 | Identified motifs for retromer interaction in the cytoplasmic domains of CI-MPR and sortilin. |
10.1073/pnas.0503689102 | 41,574,965 | sorLA (sorting protein-related receptor) is a type-1 membrane protein of unknown function that is expressed in neurons. Its homology to sorting receptors that shuttle between the plasma membrane, endosomes, and the Golgi suggests a related function in neuronal trafficking processes. Because expression of sorLA is reduc... | 10.1038/nrn2516 | A demonstration of SORLA's role as the neuronal trafficking receptor for APP and a description of a defect in this receptor's gene in the mouse. |
10.1111/j.1467-8721.2008.00570.x | 62,290,585 | The most unexpected and intriguing result from functional brain imaging studies of cognitive aging is evidence for age-related overactivation: greater activation in older adults than in younger adults, even when performance is age-equivalent. Here we examine the hypothesis that age-related overactivation is compensator... | 10.1038/nrn3256 | This paper presents the CRUNCH model of brain function and ageing, and suggests a mechanism to explain both under and over-recruitment of brain activity in older adults. |
10.1073/pnas.1015297108 | 122,599,940 | Multitasking negatively influences the retention of information over brief periods of time. This impact of interference on working memory is exacerbated with normal aging. We used functional MRI to investigate the neural basis by which an interruption is more disruptive to working memory performance in older individual... | 10.1038/nrn3256 | This study suggests the intriguing possibility that older adults show a reduced ability to resolve interference (a type of inhibition deficit) because interfering stimuli disrupt functional connectivity in task-relevant brain networks, which does not return to normal as quickly as in young adults. |
10.1196/annals.1440.011 | 62,670,226 | Thirty years of brain imaging research has converged to define the brain's default network—a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined bra... | 10.1038/nrn3256 | This review paper presents a comprehensive summary of the DN and the potential relevance of disrupted network function to dementia. |
10.1126/science.273.5283.1868 | 62,058,128 | Evoked activity in the mammalian cortex and the resulting behavioral responses exhibit a large variability to repeated presentations of the same stimulus. This study examined whether the variability can be attributed to ongoing activity. Ongoing and evoked spatiotemporal activity patterns in the cat visual cortex were ... | 10.1038/nrn3256 | An early landmark study addressing variability in brain activity by showing that intrinsic, ongoing brain activity influences the way in which stimulus-evoked activity is expressed. The authors describe the effect of such stimuli as: “the additional ripples caused by tossing a stone into a wavy sea.” |
10.1242/dev.121.9.3121 | 41,624,311 | Vertebrate neural development is initiated during gastrulation by the inductive action of the dorsal mesoderm (Spemann's organizer in amphibians) on neighbouring ectoderm, which eventually gives rise to the central nervous system from forebrain to spinal cord. Here we present evidence that bFGF can mimic the organizer ... | 10.1038/nrn2189 | References 20?22 were the first studies to implicate FGFs in neural induction. |
10.1101/gad.1153603 | 38,968,679 | How do very diverse signaling pathways induce neural differentiation in Xenopus ? Anti-BMP (Chordin), FGF8, and IGF2 signals are integrated in the embryo via the regulation of Smad1 phosphorylation. Neural induction results from the combined inhibition of BMP receptor serine/threonine kinases and activation of receptor... | 10.1038/nrn2189 | This paper integrates FGF action with the inhibition of BMP signalling proposed by the default model of neural induction in Xenopus |
10.1242/dev.127.1.177 | 41,558,964 | Current evidence suggests that the anterior segment of the vertebrate hindbrain, rhombomere 1, gives rise to the entire cerebellum. It is situated where two distinct developmental patterning mechanisms converge: graded signalling from an organising centre (the isthmus) located at the midbrain/hindbrain boundary confron... | 10.1038/nrn2189 | References 56 and 57 show that FGF8 from the MHB determines the spatial extent of adjacent brain segments, in addition to imparting their identity and polarity. |
10.1242/dev.02465 | 81,924,569 | Sonic hedgehog (SHH) is required to generate ventral cell types throughout the central nervous system. Its role in directly specifying ventral cells,however, has recently been questioned because loss of the Shh gene has little effect on ventral development if the Gli3 gene is also mutant. Consequently, another ventral ... | 10.1038/nrn2189 | A key study that shows that FGF signalling has ventralizing activity in the forebrain that is distinct from that of sonic hedgehog. |
10.1073/pnas.0337736100 | 38,196,481 | FGF8 is known to be an important regulator of forebrain development. Here, we investigated the effects of varying the level of Fgf8 expression in the mouse forebrain. We detected two distinct responses, one that was proportionate with Fgf8 expression and another that was not. The latter response, which led to effects o... | 10.1038/nrn2189 | This study emphasizes the precise dosage requirement for FGF signalling in order for it to promote neural survival in vivo |
10.1242/dev.02009 | 81,026,106 | Epiblast cells adjacent to the regressing primitive streak behave as a stem zone that progressively generates the entire spinal cord and also contributes to paraxial mesoderm. Despite this fundamental task, this cell population is poorly characterised, and the tissue interactions and signalling pathways that specify th... | 10.1038/nrn2189 | References 82 and 83 demonstrate the requirement for FGF signals in maintaining a stem-cell niche within the developing CNS. |
10.1242/dev.00978 | 60,987,078 | Induction of the otic placode, which gives rise to all tissues comprising the inner ear, is a fundamental aspect of vertebrate development. A number of studies indicate that fibroblast growth factor (Fgf), especially Fgf3, is necessary and sufficient for otic induction. However, an alternative model proposes that Fgf m... | 10.1038/nrn2189 | References 99?102 show that the same FGFs that pattern the hindbrain also induce the adjacent otic placode, thereby spatially and temporally coordinating the development of both brain and placode. |
10.1152/jn.1998.80.3.1584 | 28,102,606 | Everling, Stefan, Michael C. Dorris, and Douglas P. Munoz. Reflex suppression in the anti-saccade task is dependent on prestimulus neural processes. J. Neurophysiol. 80: 1584–1589, 1998. Reflexive responses often must be suppressed to correctly execute a voluntary behavior. It is largely unknown why this control someti... | 10.1038/nrn1345 | This study demonstrates that errors in the anti-saccade task are associated with a high level of pretarget excitation of saccade neurons in the primate superior colliculus. |
10.1152/jn.00504.2003 | 18,918,070 | The lateral intraparietal area (LIP) contains neurons that are active during the memory interval of memory saccades. We call these “persistent neurons.” Here we study the activity of the persistent neurons in memory antisaccades, “motor” (the saccade is made toward the response field, although the response field is not... | 10.1038/nrn1345 | References 32 and 33 describe paradoxical visual responses in LIP neurons in an anti-saccade task. |
10.1152/jn.00562.2002 | 122,221,165 | Previous studies have shown that the BOLD functional MRI (fMRI) signal is increased in several cortical areas when subjects perform anti-saccades compared with pro-saccades. It remains unknown, however, whether this increase is due to an increased cortical motor signal for anti-saccades or due to differences in prepara... | 10.1038/nrn1345 | Strong fMRI evidence that differences between pro-saccades and anti-saccades originate from differences in preparatory activity and not motor activity. |
10.1126/science.1978759 | 45,461,362 | Glutamate has been found to play an unexpectedly important role in neuroendocrine regulation in the hypothalamus, as revealed in converging experiments with ultrastructural immunocytochemistry, optical physiology with a calcium-sensitive dye, and intracellular electrical recording. There were large amounts of glutamate... | 10.1038/nrn3881 | This was the first demonstration of glutamate as a fast, excitatory synaptic signal in the PVN. |
10.1126/science.1095505 | 41,741,062 | Neural stem cells are reported to lie in a vascular niche, but there is no direct evidence for a functional relationship between the stem cells and blood vessel component cells. We show that endothelial cells but not vascular smooth muscle cells release soluble factors that stimulate the self-renewal of neural stem cel... | 10.1038/nrn2761 | This study provided data suggesting the presence of an endothelial niche that regulates NSC activity in the brain. |
10.1101/gad.1616208 | 123,112,819 | Neural stem cells (NSCs) yield both neuronal and glial progeny, but their differentiation potential toward multiple region-specific neuron types remains remarkably poor. In contrast, embryonic stem cell (ESC) progeny readily yield region-specific neuronal fates in response to appropriate developmental signals. Here we ... | 10.1038/nrn2761 | This study was the first to demonstrate that hESC-derived neural rosettes can be maintained for some passages in vitro by SHH and Notch receptor agonists. In the same paper it was also shown that this cell population can also be directly isolated, by means of the combination of Forse-1 and N-cadherin cell-sorting strat... |
10.1073/pnas.0808387106 | 58,402,431 | An intriguing question in human embryonic stem cell (hESC) biology is whether these pluripotent cells can give rise to stably expandable somatic stem cells, which are still amenable to extrinsic fate instruction. Here, we present a pure population of long-term self-renewing rosette-type hESC-derived neural stem cells (... | 10.1038/nrn2761 | This paper demonstrated that a well-defined hESC-derived population of post-rosette-stage neuroepithelial cells can retain some developmental plasticity following long-term propagation in the presence of EGF and FGF2. |
10.1126/science.1553558 | 123,058,509 | Neurogenesis in the mammalian central nervous system is believed to end in the period just after birth; in the mouse striatum no new neurons are produced after the first few days after birth. In this study, cells isolated from the striatum of the adult mouse brain were induced to proliferate in vitro by epidermal growt... | 10.1038/nrn2761 | This landmark paper was the first to report culture conditions that allow the in vitro expansion (in a neurosphere system) of multipotent stem or progenitor cells present in the adult mammalian brain. |
10.1073/pnas.96.17.9932 | 40,067,626 | Exogenous application of agonists at the kainate subtype of glutamate receptors has been shown to depress evoked monosynaptic inhibition by γ-aminobutyric acid (GABA)ergic interneurons in the hippocampus. This observation has led to the hypothesis that synaptic release of endogenous glutamate might have a disinhibitory... | 10.1038/nrn1118 | Examines the effect of synaptically released glutamate on monosynaptic inhibitory signalling. Describes that brief bursts of activity in glutamatergic afferent fibres reduce GABA-mediated transmission. Concludes that the net kainate receptor-mediated effect of synaptically released glutamate is to reduce monosynaptic i... |
10.1073/pnas.90.24.11688 | 16,765,125 | Glutamate mediates fast synaptic transmission at the majority of excitatory synapses throughout the central nervous system by interacting with different types of receptor channels. Cloning of glutamate receptors has provided evidence for the existence of several structurally related subunit families, each composed of s... | 10.1038/nrn1118 | Provided the first functional evidence that there are pure kainate receptors in central neurons. |
10.1128/aem.60.5.1565-1571.1994 | 20,723,311 | Euprymna scolopes, a Hawaiian species of bioluminescent squid, harbors Vibrio fischeri as its specific light organ symbiont. The population of symbionts grew inside the adult light organ with an average doubling time of about 5 h, which produced an excess of cells that were expelled into the surrounding seawater on a d... | 10.1038/nrmicro957 | Demonstrated that populations of the squid host dramatically influence the concentration of V. fischeri in the bacterioplankton, which in turn affects the efficiency with which juvenile squid are colonized at hatching. |
10.1073/pnas.97.18.10231 | 103,976,709 | While most animal–bacterial symbioses are reestablished each successive generation, the mechanisms by which the host and its potential microbial partners ensure tissue colonization remain largely undescribed. We used the model association between the squid Euprymna scolopes and Vibrio fischeri to examine this process. ... | 10.1038/nrmicro957 | Provided the first mechanism by which an aquatic animal could harvest relatively scarce symbionts from the environment. |
10.1146/annurev.micro.50.1.591 | 29,131,179 | Although the study of microbe-host interactions has been traditionally dominated by an interest in pathogenic associations, there is an increasing awareness of the importance of cooperative symbiotic interactions in the biology of many bacteria and their animal and plant hosts. This review examines a model system for t... | 10.1038/nrmicro957 | Compares the colonization determinants of pathogenic and beneficial vibrios, and outlines the genetic tools available in Vibrio fischeri |
10.1113/jphysiol.1972.sp009698 | 124,756,939 | 1. In foetal lambs from 40 days gestation (0·27 of term) onwards delivered into a warm saline bath, apparently spontaneous breathing movements were present intermittently. They became deeper and more rapid with increasing age. 2. In foetal lambs (from 0·66 of term) in which observations were made for many days after ch... | 10.1038/nrn2716 | A technical tour de force that documents the occurrence of brain activation in utero |
10.1093/oso/9780195126877.003.0003 | 149,032,306 | Abstract A mind when functioning well is designed, on most every view, be it theistic or naturalistic, to track reality, to provide reliable information about the world-to yield the truth. The mind’s job is to help us live well as “living well” is conceived by the relevant background theory. | 10.1038/nrn2716 | A serious philosophical suggestion that dreaming itself may be epiphenomenal. |
10.1126/science.3629249 | 123,894,114 | Contemporary research in cognitive psychology reveals the impact of nonconscious mental structures and processes on the individual's conscious experience, thought, and action. Research on perceptual-cognitive and motoric skills indicates that they are automatized through experience, and thus rendered unconscious. In ad... | 10.1038/nrn2716 | A review of the evidence indicating that much adaptive information processing is not conscious. |
10.1098/rspb.1912.0051 | 79,769,446 | In a communication upon the intrinsic factors in progression presented to the Society in July of last year the author drew the conclusion that the rhythm of progression is of central origin. In then enquiring into the nature of that central origin Re suggested that the movements are determined by a balance between equa... | 10.1038/nrn2716 | This report claims that oscillators (or clocks) are as fundamental as reflexes in determining CNS activity. |
10.1523/jneurosci.1378-09.2009 | 62,545,676 | Previous research indicates a critical role of the hippocampus in memory for events in the context in which they occur. However, studies to date have not provided compelling evidence that hippocampal neurons encode event–context conjunctions directly associated with this kind of learning. Here we report that, as animal... | 10.1038/nrn3492 | This paper reveals that in rats, hippocampal neurons exhibit context-dependent firing patterns that represent odour–reward associations in specific places. |
10.1523/jneurosci.1651-08.2008 | 122,358,016 | Lesion studies in animals have identified a critical role of the hippocampus in context fear conditioning. To extend these findings to human volunteers, we used functional magnetic resonance imaging to investigate neural responses associated with context fear conditioning in humans. Our novel conditioning paradigm cons... | 10.1038/nrn3492 | This paper differentiates amygdala and hippocampal activity during cued and context fear conditioning in humans. |
10.1523/jneurosci.2021-06.2006 | 102,331,993 | In fear extinction, an animal learns that a conditioned stimulus (CS) no longer predicts a noxious stimulus [unconditioned stimulus (UCS)] to which it had previously been associated, leading to inhibition of the conditioned response (CR). Extinction creates a new CS–noUCS memory trace, competing with the initial fear (... | 10.1038/nrn3492 | This study is among the first to report that the ventromedial prefrontal–hippocampal network is involved in context-dependent recall of human extinction memory. |
10.1002/hipo.20954 | 60,871,667 | Abstract Fear can be extinguished by repeated exposure to a cue that signals threat. However, extinction does not erase fear, as an extinguished cue presented in a context distinct from that of extinction results in renewed fear of that cue. The hippocampus, which is involved in the formation of contextual representati... | 10.1038/nrn3492 | This paper reveals that the hippocampus has a critical role in the context-dependent retrieval of extinction memories but that animals that underwent extinction without a hippocampus exhibit contextual control under some conditions. |
10.1073/pnas.1202087109 | 101,457,854 | The memory of fear extinction is context dependent: fear that is suppressed in one context readily renews in another. Understanding of the underlying neuronal circuits is, therefore, of considerable clinical relevance for anxiety disorders. Prefrontal cortical and hippocampal inputs to the amygdala have recently been s... | 10.1038/nrn3492 | This study uses a novel transgenic rat to localize convergent hippocampal and prefrontal projections onto amygdala neurons that are differentially active during the expression of extinction or during the renewal of fear. |
10.1152/physrev.1997.77.4.1165 | 122,713,663 | The properties and roles of ATP-sensitive (KATP) and inwardly rectifying (KIR) potassium channels are reviewed. Potassium channels regulate the membrane potential of smooth muscle, which controls calcium entry through voltage-dependent calcium channels, and thereby contractility through changes in intracellular calcium... | 10.1038/nrn1246 | An encyclopaedic review of K+ channels that are involved in regulation of the vasculature. |
10.1161/01.atv.21.1.28 | 124,038,336 | Abstract —Potassium ion (K + ) channel activity is a major regulator of vascular muscle cell membrane potential ( E m ) and is therefore an important determinant of vascular tone. There is growing evidence that the function of several types of vascular K + channels is altered during major cardiovascular diseases, such ... | 10.1038/nrn1246 | This review describes the variety of K+ channels that are involved in the control of vascular tone, specifically focusing on how they can be altered by hypertension, diabetes and hypercholesterolaemia. |
10.1162/089892900564046 | 28,247,851 | Brain imaging based on functional MRI (fMRI) provides a powerful tool for characterizing age-related changes in functional anatomy. However, between-population comparisons confront potential differences in measurement properties. The present experiment explores the feasibility of conducting fMRI studies in nondemented ... | 10.1038/nrn1246 | An important paper that examined the haemodynamic response characteristics and summation properties of sensorimotor and visual cortex in young, healthy older and demented older patients. Regional haemodynamic differences were observed but summation properties were preserved across groups. |
10.1161/hs0102.100482 | 82,173,877 | Background and Purpose — Blood oxygenation level–dependent (BOLD) functional MRI (fMRI) is a promising method for defining brain recovery after stroke quantitatively. Applications thus far have assumed that the BOLD hemodynamic response in patients after stroke is identical to that in healthy controls. However, because... | 10.1038/nrn1246 | One of the first studies to investigate BOLD haemodynamic response characteristics in patients with subcortical strokes. It indicates that BOLD signal changes might result from diffuse microvascular changes in certain patient populations. |
10.1146/annurev.psych.50.1.243 | 38,368,995 | ▪ Abstract Three areas of high-level scene perception research are reviewed. The first concerns the role of eye movements in scene perception, focusing on the influence of ongoing cognitive processing on the position and duration of fixations in a scene. The second concerns the nature of the scene representation that i... | 10.1038/nrn1476 | A systematic review that elaborates on the opposition to the notion that context can facilitate object recognition. |
10.1162/089892903321662976 | 62,247,203 | The majority of the research related to visual recognition has so far focused on bottom-up analysis, where the input is processed in a cascade of cortical regions that analyze increasingly complex information. Gradually more studies emphasize the role of top-down facilitation in cortical analysis, but it remains someth... | 10.1038/nrn1476 | Describes some of the conceptual bases for the model of contextual facilitation that is proposed in this review. |
10.1111/j.1467-9280.1994.tb00500.x | 125,120,496 | In very fast recognition tasks, scenes are identified as fast as isolated objects How can this efficiency be achieved, considering the large number of component objects and interfering factors, such as cast shadows and occlusions? Scene categories tend to have distinct and typical spatial organizations of their major c... | 10.1038/nrn1476 | An elegant study showing that observers can categorize a scene briefly on the basis of the low-spatial-frequency content in the image. |
10.1146/annurev.neuro.27.070203.144130 | 83,500,126 | ▪ Abstract The medial temporal lobe includes a system of anatomically related structures that are essential for declarative memory (conscious memory for facts and events). The system consists of the hippocampal region (CA fields, dentate gyrus, and subicular complex) and the adjacent perirhinal, entorhinal, and parahip... | 10.1038/nrn1476 | A clear and thorough review of the controversy surrounding the functional distinction of the various sub-regions within the medial temporal lobe. |
10.1128/aem.66.2.578-587.2000 | 41,698,329 | ABSTRACT Bacterial community composition, enzymatic activities, and carbon dynamics were examined during diatom blooms in four 200-liter laboratory seawater mesocosms. The objective was to determine whether the dramatic shifts in growth rates and ectoenzyme activities, which are commonly observed during the course of p... | 10.1038/nrmicro3326 | This is one of the initial papers that reports the phenotypic and phylogenetic changes that occur to the bacterial community during the formation and decay of a phytoplankton bloom. |
10.1146/annurev-marine-120710-100827 | 38,395,502 | Genomic and functional genomic methods applied to both model organisms and natural communities have rapidly advanced understanding of bacterial dimethylsulfoniopropionate (DMSP) degradation in the ocean. The genes for the two main pathways in bacterial degradation, routing DMSP to distinctly different biogeochemical fa... | 10.1038/nrmicro3326 | This is a comprehensive review of DMSP transformation pathways in marine bacteria. |
10.1073/pnas.1102457108 | 107,159,260 | Marine microgels play an important role in regulating ocean basin-scale biogeochemical dynamics. In this paper, we demonstrate that, in the high Arctic, marine gels with unique physicochemical characteristics originate in the organic material produced by ice algae and/or phytoplankton in the surface water. The polymers... | 10.1038/nrmicro3326 | This study reports the role of microgels (which are produced by phytoplankton) in cloud formation and their possible effects on climate. |
10.1073/pnas.1403051111 | 13,469,713 | Significance Ion-translocating, light-activated membrane proteins known as rhodopsins are found in all three domains of life. Proton-pumping rhodopsins, such as proteorhodopsin, are known to be broadly distributed in marine bacteria. The first known sodium-pumping rhodopsin was recently described in marine flavobacteri... | 10.1038/nrmicro3326 | This paper describes the first example of a rhodopsin chloride pump found in flavobacteria. |
10.1523/jneurosci.5693-09.2010 | 17,714,843 | Endocannabinoids (eCBs) function as retrograde signaling molecules at synapses throughout the brain, regulate axonal growth and guidance during development, and drive adult neurogenesis. There remains a lack of genetic evidence as to the identity of the enzyme(s) responsible for the synthesis of eCBs in the brain. Diac... | 10.1038/nrn3846 | This paper reports the generation of DAGL-null mice and provides genetic evidence on the requirement of DAGL function for continued neurogenesis in the mouse forebrain during postnatal life. |
10.1126/science.1470919 | 20,870,598 | Arachidonylethanolamide, an arachidonic acid derivative in porcine brain, was identified in a screen for endogenous ligands for the cannabinoid receptor. The structure of this compound, which has been named "anandamide," was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed b... | 10.1038/nrn3846 | In this paper, the authors identify anandamide as the first endogenous ligand of CB1Rs in the brain. This landmark paper marks the advent of contemporary endocannabinoid research. |
10.1523/jneurosci.3101-05.2006 | 123,242,389 | Endocannabinoids exert an important neuromodulatory role via presynaptic cannabinoid CB 1 receptors and may also participate in the control of neural cell death and survival. The function of the endocannabinoid system has been extensively studied in differentiated neurons, but its potential role in neural progenitor ce... | 10.1038/nrn3846 | This paper provides the molecular identity and describes the expression sites and signalling mechanisms of cannabinoid receptors and the key metabolic enzymes for endocannabinoids in astroglia. Moreover, it establishes the role of endocannabinoids in cell fate decisions and lineage commitment. |
10.1126/science.1137406 | 80,140,146 | The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB 1 cannabinoid receptors (CB 1 Rs) are enriched in the axonal growth cones of γ-aminobutyric acid–containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB 1 R... | 10.1038/nrn3846 | In this paper, the authors show that axonal CB1Rs can sense extracellular ligand gradients and can induce growth cone repulsion or collapse. This mechanism is then implicated in disrupted synaptogenesis in the cortex of mice lacking CB1Rs in GABAergic cortical interneurons. |
10.1111/j.0021-8782.2004.00325.x | 100,480,256 | Abstract The role of the CB1 cannabinoid receptor and endocannabinoid signalling has been widely studied in the adult nervous system. However, an emerging body of evidence suggests that the CB1 receptor may also play a role during development. Here we have scrutinized the expression profile of the CB1 receptor from the... | 10.1038/nrn3846 | This paper reports that neuronal commitment coincides with the upregulation of CB1R in the earliest-born neurons of the chick embryo. This proposal led to subsequent mechanistic studies implicating CB1R functions in a broad range of developmental processes. |
10.1083/jcb.200305129 | 124,853,158 | Diacylglycerol (DAG) lipase activity is required for axonal growth during development and for retrograde synaptic signaling at mature synapses. This enzyme synthesizes the endocannabinoid 2-arachidonoyl-glycerol (2-AG), and the CB1 cannabinoid receptor is also required for the above responses. We now report on the clon... | 10.1038/nrn3846 | This paper identifies the DAGLs, shows their distribution in both the developing and adult nervous system and suggests a striking switch in DAGL expression sites during synaptogenesis. The substrate and product specificity of DAGL is also defined. |
10.1126/science.1152662 | 47,988,898 | Cannabinoid receptor 1 (CB1R) regulates neuronal differentiation. To understand the logic underlying decision-making in the signaling network controlling CB1R-induced neurite outgrowth, we profiled the activation of several hundred transcription factors after cell stimulation. We assembled an in silico signaling networ... | 10.1038/nrn3846 | In this paper, the authors define a minimal transcription factor network downstream from CB1Rs that is required for neurite outgrowth. They also implicate BRCA1 in cannabinoid signalling, which was shown as a candidate to control MAGL stability by Keimpema in 2013. |
10.1083/jcb.200210164 | 81,339,017 | Akey role for DAG lipase activity in the control of axonal growth and guidance in vitro and in vivo has been established. For example, DAG lipase activity is required for FGF-stimulated calcium influx into neuronal growth cones, and this response is both necessary and sufficient for an axonal growth response. The mecha... | 10.1038/nrn3846 | In this paper, the authors suggest that endocannabinoid signalling is regulated by FGFRs and that this coupling underpins FGF-induced neurite outgrowth. |
10.1073/pnas.96.10.5780 | 81,900,780 | Δ 9 -Tetrahydrocannabinol (Δ 9 -THC), the major psychoactive ingredient in preparations of Cannabis sativa (marijuana, hashish), elicits central nervous system (CNS) responses, including cognitive alterations and euphoria. These responses account for the abuse potential of cannabis, while other effects such as analgesi... | 10.1038/nrn3846 | This paper describes the initial characterization of CB1R-null mice, showing their premature death during aging. However, this study failed to identify developmental abnormalities. |
10.1126/science.3453112 | 60,054,180 | The primary structure of human uromodulin, a 616-amino acid, 85-kilodalton glycoprotein with in vitro immunosuppressive properties, was determined through isolation and characterization of complementary DNA and genomic clones. The amino acid sequence encoded by one of the exons of the uromodulin gene has homology to th... | 10.1038/nrneph.2017.101 | Identification of uromodulin as Tamm-Horsfall glycoprotein and of its key properties, including glycosylation and kidney-specific synthesis. |
10.1038/ncomms10023 | 104,112,071 | Abstract Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 4... | 10.1038/nrneph.2017.101 | The largest meta-analysis for eGFR and CKD reported so far, demonstrating the predominant size effect of the UMOD locus. |
10.1073/pnas.1519803113 | 102,950,791 | Uromodulin (UMOD)/Tamm–Horsfall protein, the most abundant human urinary protein, plays a key role in chronic kidney diseases and is a promising therapeutic target for hypertension. Via its bipartite zona pellucida module (ZP-N/ZP-C), UMOD forms extracellular filaments that regulate kidney electrolyte balance and innat... | 10.1038/nrneph.2017.101 | Crystal structure of uromodulin suggesting the possible mechanism of polymerization. |
10.1152/ajprenal.00143.2004 | 102,917,112 | The Tamm-Horsfall protein (THP; uromodulin), the dominant protein in normal urine, is produced exclusively in the thick ascending limb of Henle's loop. THP mutations are associated with disease; however, the physiological role of THP remains obscure. We generated THP gene-deficient mice (THP −/−) and compared them with... | 10.1038/nrneph.2017.101 | Study of the effects of lack of uromodulin on murine kidney physiology. |
10.1042/cs0680529 | 28,931,322 | 1. A recently developed, simple and sensitive radioimmunoassay has been used to examine 24 h excretion and plasma levels of Tamm-Horsfall glycoprotein (THG) in normal subjects, stone formers and patients with stable chronic renal disease. 2. In normal subjects THG excretion ranged from 22 to 66 mg/24 h, with no sex dif... | 10.1038/nrneph.2017.101 | Demonstration of a correlation between plasma and urine levels of uromodulin; differences in concentrations; and influence by CKD. |
10.1242/dmm.029488 | 38,503,873 | Renal fibrosis is a common feature of renal failure resulting from multiple aetiologies, including diabetic nephropathy, hypertension and inherited renal disorders. However, the mechanisms of renal fibrosis are incompletely understood and we therefore explored these by establishing a mouse model for a renal tubular dis... | 10.1038/nrneph.2017.101 | First knock-in mouse model of uromodulin-associated kidney disease, with ER stress as a key pathogenic mechanism. |
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