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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10.1101/gad.852400 | 82,117,971 | Spatial variations in the levels of bone morphogenetic protein (BMP) signaling are a critical determinant of dorsoanterior-ventroposterior pattern in vertebrate embryos. Whereas BMP overexpression abolishes both head and trunk development, known single and double loss-of-function mutations in BMP inhibitors have less d... | 10.1038/nrn786 | Zebrafish double mutants for chordin and bozozok showed synergistic elimination of head and trunk structures. Chordin blocks BMP activity extracellularly and bozozok is a homeobox gene that acts to repress bmp2 and wnt expression. The genetic inactivation of BMP signalling suppressed the defects of the chordino/bozozok... |
10.1073/pnas.97.21.11307 | 19,282,051 | Human embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of in vitro fertilized human blastocysts. We examined the potential of eight growth factors [basic fibroblast growth factor (bFGF), transforming growth factor β1 (TGF-β1), activin-A, bone morphogenic protein 4 (BMP-4), hepatocyte gro... | 10.1038/nrn786 | The first attempt to use exogenous growth factors to mediate the determination of cell fates in human ES cells. It highlighted the conservation of molecular pathways during vertebrate embryogenesis, and indicated pathways that might be used during embryogenesis to direct the differentiation of human ES cells. |
10.1111/1469-7610.00034 | 40,058,570 | Background: This article selectively reviews the biological bases of antisocial and aggressive behavior in children with a focus on low autonomic functioning, prefrontal deficits, and early health factors. Results: Low resting heart rate is thought to be the best‐replicated biological correlate of antisocial and aggres... | 10.1038/nrn2174 | This paper was the first to review the importance of reduced autonomic arousal in the development of antisocial and aggressive behaviour in children. |
10.1111/j.1749-6632.1999.tb09271.x | 41,704,481 | ABSTRACT: Hormonal and chemosensory signals regulate social behaviors in a wide variety of mammals. In the male Syrian hamster, these signals are integrated in nuclei of the medial extended amygdala, where olfactory and vomeronasal system transmission is modulated by populations of androgen‐ and estrogen‐sensitive neur... | 10.1038/nrn2174 | This review summarizes studies that examined the social behaviour brain circuit and highlights how brain nuclei function in different contexts. |
10.1046/j.1460-9568.2003.02447.x | 41,299,699 | Abstract Autonomic and limbic neural activities are linked to aggressive behavior, and it is hypothesized that activities in the cardiovascular and monoaminergic systems play a role in preparing for an aggressive challenge. The objective was to learn about the emergence of monoamine activity in nucleus accumbens before... | 10.1038/nrn2174 | This study is unique because it measures dynamic changes in neurotransmitter levels during aggressive encounters in male rats. Interestingly, when aggression tests were regularly scheduled, increased dopamine and decreased 5-HT levels were observed in anticipation of aggressive encounters. |
10.1146/annurev.neuro.22.1.197 | 103,818,825 | ▪ Abstract Cloning of MAO (monoamine oxidase) A and B has demonstrated unequivocally that these enzymes are made up of different polypeptides, and our understanding of MAO structure, regulation, and function has been significantly advanced by studies using their cDNA. MAO A and B genes are located on the X-chromosome (... | 10.1038/nrn2174 | This review summarizes converging evidence for the roles of MAOA and MAOB in the regulation of aggressive behaviour in mice. |
10.1126/science.1072290 | 26,771,260 | We studied a large sample of male children from birth to adulthood to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not. A functional polymorphism in the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A ( MAOA ) was found to moderate t... | 10.1038/nrn2174 | This report helped spark renewed interest in studying the mechanisms of gene–environment interactions in humans. It shows that individuals that are homozygous for the short allele of the 5-HT transporter promoter are more likely to suffer mental disorders, but only if they were maltreated as children. |
10.1073/pnas.0601674103 | 79,438,630 | The effect of life stress on depression is moderated by a repeat length variation in the transcriptional control region of the serotonin transporter gene, which renders carriers of the short variant vulnerable for depression. We investigated the underlying neural mechanisms of these epigenetic processes in individuals ... | 10.1038/nrn2174 | This study looked at how the interaction between the 5-HT transporter and the environment influences brain function. Life stressors were found to affect functional connectivity in the amygdala and hippocampus as a function of 5-HT transporter genotype. |
10.1073/pnas.0701819104 | 124,692,670 | Despite recent discoveries of the specific contributions of genes to behavior, the molecular mechanisms mediating contributions of the environment are understudied. We demonstrate that the behavioral effects of estrogens on aggression are completely reversed by a discrete environmental signal, day length. Selective act... | 10.1038/nrn2174 | This study used a precise environmental factor, day length, to probe gene function. When beach mice were exposed to 16 hours of light each day, oestrogen hormones decreased aggression, but when mice were exposed to only 8 hours of light each day, oestrogen hormones acted rapidly to increase aggression. |
10.1113/jphysiol.2007.149336 | 20,558,622 | Silent synapses are synapses whose activation evokes NMDA‐type glutamate receptor (NMDAR) but not AMPA‐type glutamate receptor (AMPAR) mediated currents. Silent synapses are prominent early in postnatal development and are thought to play a role in the activity‐ and sensory‐dependent refinement of neuronal circuits. Th... | 10.1038/nrn2501 | By using glutamate uncaging to trigger uEPSCs and thus to bypass the presynaptic terminal, this paper was the first to demonstrate unequivocally that silent synapses express no functional AMPARs in the postsynaptic membrane. |
10.1126/science.284.5421.1811 | 104,258,151 | To monitor changes in α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor distribution in living neurons, the AMPA receptor subunit GluR1 was tagged with green fluorescent protein (GFP). This protein (GluR1-GFP) was functional and was transiently expressed in hippocampal CA1 neurons. In dendrites visualiz... | 10.1038/nrn2501 | In hippocampal neurons that expressed a recombinant GluR1 AMPAR subunit tagged with GFP, these authors observed rapid delivery of tagged receptors to the postsynaptic membrane from intracellular stores following LTP induction, providing evidence that LTP occurs by trafficking AMPARs to synapses. |
10.1073/pnas.0700286104 | 61,698,306 | Animals house a community of bacterial symbionts in their digestive tracts that contribute to their well being. The medicinal leech, Hirudo verbana , has a remarkably simple gut population carrying two extracellular microbes in the crop where the ingested blood is stored. This simplicity renders it attractive for study... | 10.1038/nrmicro2894 | This study shows that a bacterial T3SS is required for both symbiotic competence and virulence in different animal hosts. |
10.1111/j.1462-2920.2008.01788.x | 82,394,593 | Summary The light organ crypts of the squid Euprymna scolopes permit colonization exclusively by the luminous bacterium Vibrio fischeri. Because the crypt interior remains in contact with seawater, the squid must not only foster the specific symbiosis, but also continue to exclude other bacteria. Investigation of the r... | 10.1038/nrmicro2894 | This work finds that colonization of the squid light organ might contribute to immune tolerance of the symbiont V. fischeri |
10.1126/science.1068883 | 62,555,470 | The innate immune system evolved several strategies of self/nonself discrimination that are based on the recognition of molecular patterns demarcating infectious nonself, as well as normal and abnormal self. These patterns are deciphered by receptors that either induce or inhibit an immune response, depending on the me... | 10.1038/nrmicro2894 | This paper highlights the concept of PAMPs and the importance of pattern recognition in innate immunity. |
10.1126/science.1102218 | 102,669,627 | Tracheal cytotoxin (TCT), a fragment of the bacterial surface molecule peptidoglycan (PGN), is the factor responsible for the extensive tissue damage characteristic of whooping cough and gonorrhea infections. Here, we report that Vibrio fischeri also releases TCT, which acts in synergy with lipopolysaccharide (LPS) to ... | 10.1038/nrmicro2894 | This article coins the term MAMP and shows that a bacterial toxin can be used as a signalling molecule to induce normal host development. |
10.1073/pnas.0703375104 | 41,493,976 | Epithelia in animals are colonized by complex communities of microbes. Although a topic of long-standing interest, understanding the evolution of the microbial communities and their role in triggering innate immune responses has resisted analysis. Cnidaria are among the simplest animals at the tissue grade of organizat... | 10.1038/nrmicro2894 | The results from this study suggest that Hydra spp. can actively determine the composition of their microbiota. |
10.1126/science.1071059 | 125,224,848 | For over 50 years immunologists have based their thoughts, experiments, and clinical treatments on the idea that the immune system functions by making a distinction between self and nonself. Although this paradigm has often served us well, years of detailed examination have revealed a number of inherent problems. This ... | 10.1038/nrmicro2894 | This paper highlights the danger model and the importance of DAMPs in the immune response. |
10.1152/jn.2001.86.1.402 | 29,192,012 | It is well accepted that pain is a multidimensional experience, but little is known of how the brain represents these dimensions. We used positron emission tomography (PET) to indirectly measure pain-evoked cerebral activity before and after hypnotic suggestions were given to modulate the perceived intensity of a painf... | 10.1038/nrn3538 | The second of two, now classic, studies in which hypnotic suggestions targeting either the affective or the sensory components of a physically induced pain experience resulted in activation in selective and different areas of the brain. |
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/nrn3538 | Using examples from automatic processes, subliminal perception, implicit memory and hypnosis, this influential paper helped to generate renewed interest in cognitive structures and processes outside conscious awareness. |
10.1073/pnas.1200575109 | 17,598,149 | We used in vivo amperometry to monitor changes in synaptic dopamine (DA) release in the striatum induced by overexpression of human wild-type α-synuclein in nigral DA neurons, induced by injection of an adeno-associated virus type 6 (AAV6)–α-synuclein vector unilaterally into the substantia nigra in adult rats. Impairm... | 10.1038/nrn.2017.75 | This study uses in vivo amperometry to measure dopamine changes in the striatum and shows that α-syn is involved in synaptic dopamine release in the basal ganglia. |
10.1126/science.1245296 | 18,958,028 | From Yeast to Therapeutic? Yeast has shown some promise as a model system to generate lead compounds that could have therapeutic potential for the cellular problems associated with neurodegenerative diseases. Along these lines, Tardiff et al. (p. 979 , published online 24 October) and Chung et al. (p. 983 , published o... | 10.1038/nrn.2017.75 | This important paper shows how patient-derived neurons and yeast models of α-synucleinopathy can direct drug target discovery programmes. |
10.1073/pnas.1309143110 | 41,288,904 | Significance Elevated expression of the presynaptic protein α-synuclein underlies familial and sporadic Parkinson disease (PD). However, our understanding of how increases in α-synuclein levels drive the sequence of events leading to PD is incomplete. Here, we apply a multidisciplinary longitudinal analysis to a new α-... | 10.1038/nrn.2017.75 | This key paper describes early events leading up to neurodegeneration, enhancing our understanding of physiological responses to α-syn overexpression. |
10.1126/science.1227157 | 20,881,057 | Synthetic Parkinson's Parkinson's disease (PD) and related α-synucleinopathies are defined by the accumulation of α-synuclein (α-Syn)–containing intraneuronal inclusions—Lewy bodies (LBs) and Lewy neurites (LNs)—in association with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and other ... | 10.1038/nrn.2017.75 | This study highlights how spreading of α-syn can occur in the normal mammalian brain, with implications for mechanisms of multisystem involvement in human PD. |
10.1073/pnas.0636123100 | 60,536,626 | The vomeronasal organ (VNO) detects pheromones in many vertebrate species but is likely to be vestigial in humans. TRPC2(TRP2) , a gene that is essential for VNO function in the mouse, is a pseudogene in humans. Because TRPC2 is expressed only in the VNO, the loss of selective pressure on this gene can serve as a molec... | 10.1038/nrn1140 | This detailed sequence analysis of the Trp2 gene across the evolutionary tree of primates provides a strong molecular argument for a progressive loss of the requirement for VNO function in Old World monkeys. |
10.1126/science.289.5484.1569 | 16,748,579 | The vomeronasal organ (VNO) of mammals plays an essential role in the detection of pheromones. We obtained simultaneous recordings of action potentials from large subsets of VNO neurons. These cells responded to components of urine by increasing their firing rate. This chemosensory activation required phospholipase C f... | 10.1038/nrn1140 | The recording of action potentials from VNO neurons with a flat electrode array permitted a systematic analysis of the response of large populations of VNO neurons to pheromonal stimuli, indicating striking differences in mechanisms of odorant detection by MOE neurons. |
10.1073/pnas.082127599 | 123,929,733 | We have used gene targeting to generate mice with a homozygous deficiency in trp2, a cation channel expressed in the vomeronasal organ (VNO). Trp2 mutant animals reveal a striking reduction in the electrophysiological response to pheromones in the VNO, suggesting that trp2 plays a central role in mediating the pheromon... | 10.1038/nrn1140 | References 68 and 69 describe the analysis of mutant mouse lines that are deficient in the Trp2 channel. They demonstrate a requirement for Trp2 function in the pheromone-evoked response and point to an exclusive role for the VNO in controlling aggressive behaviour, territorial marking and gender discrimination. |
10.1126/science.1082133 | 104,116,317 | Many mammalian species rely on pheromones—semiochemicals produced by other members of the same species—to communicate social status and reproductive readiness. To assess how the central nervous system integrates the complex repertoire of pheromones, we recorded from single neurons in the accessory olfactory bulb, a nuc... | 10.1038/nrn1140 | Recording of AOB mitral cells in the living mouse provided a unique description of the specificity of mitral cell activation in response to male and female conspecifics mice of various strains. |
10.1126/science.274.5292.1527 | 103,816,661 | Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in... | 10.1038/nrn2284 | This paper provided the first demonstration that a functional-repeat length variation in the transcriptional control region of the SLC6A4 gene is associated with anxiety-, depression-, and aggression-related personality traits. The authors also suggest a hypothesis for the SERT-specific genetic susceptibility of affect... |
10.1126/science.1101678 | 104,237,493 | Reduced serotonin transporter (5-HTT) expression is associated with abnormal affective and anxiety-like symptoms in humans and rodents, but the mechanism of this effect is unknown. Transient inhibition of 5-HTT during early development with fluoxetine, a commonly used serotonin selective reuptake inhibitor, produced ab... | 10.1038/nrn2284 | This work provided evidence that transient pharmacological inhibition of SERT during early development produced abnormal emotional behaviours in adult mice and thus mimicked the behavioural phenotype of Slc6a4 -mutant mice. The results suggest that a developmental mechanism explains how low SERT function increases vuln... |
10.1073/pnas.95.13.7699 | 103,860,413 | Cocaine and methylphenidate block uptake by neuronal plasma membrane transporters for dopamine, serotonin, and norepinephrine. Cocaine also blocks voltage-gated sodium channels, a property not shared by methylphenidate. Several lines of evidence have suggested that cocaine blockade of the dopamine transporter (DAT), pe... | 10.1038/nrn2284 | This paper, together with reference 66, used double-knockout mice to provide the first evidence that cocaine reward and dependence is mediated by both the dopamine transporter and SERT. |
10.1126/science.1083968 | 20,668,598 | In a prospective-longitudinal study of a representative birth cohort, we tested why stressful experiences lead to depression in some people but not in others. A functional polymorphism in the promoter region of the serotonin transporter (5-HT T) gene was found to moderate the influence of stressful life events on depre... | 10.1038/nrn2284 | This paper, together with strong replications (references 9 and 22), proposed that the effect of SLC6A4 -gene variation on depression risk in humans interacts with psychosocial stress. It also confirmed the findings in non-human-primate and rodent models of the existence of a neurodevelopmentally critical period of ear... |
10.1073/pnas.0601674103 | 79,438,630 | The effect of life stress on depression is moderated by a repeat length variation in the transcriptional control region of the serotonin transporter gene, which renders carriers of the short variant vulnerable for depression. We investigated the underlying neural mechanisms of these epigenetic processes in individuals ... | 10.1038/nrn2284 | This study, together with reference 108, used high-resolution functional MRI to demonstrate that serotonin transport efficiency is important for brain processes involving neural systems that control affective, cognitive and motor processes. The authors also showed that life stress differentially moderates the functiona... |
10.1002/ana.10105 | 84,442,101 | Abstract Memory function commonly declines in later life. Whether memory decline represents a disease process or whether it is part of normal aging remains unknown. Here we answer this question by assessing the function of multiple subregions that make up the hippocampal circuit across the human life span. A newly deve... | 10.1038/nrn1323 | A provocative paper that used structural imaging to show differential influences of normal ageing and pathology on hippocampal subregions. |
10.1162/089892900561814 | 20,882,148 | Age-related decline in working memory figures prominently in theories of cognitive aging. However, the effects of aging on the neural substrate of working memory are largely unknown. Positron emission tomography (PET) was used to investigate verbal and spatial short-term storage (3 sec) in older and younger adults. Pre... | 10.1038/nrn1323 | This study first suggested that bilateral activity in older adults might be due to compensatory mechanisms. |
10.1146/annurev.neuro.22.1.105 | 41,728,686 | ▪ Abstract The hippocampus is a target of stress hormones, and it is an especially plastic and vulnerable region of the brain. It also responds to gonadal, thyroid, and adrenal hormones, which modulate changes in synapse formation and dendritic structure and regulate dentate gyrus volume during development and in adult... | 10.1038/nrn1555 | A comprehensive review of the pioneer studies in which stress and glucocorticoids were shown to affect hippocampal structure and function. |
10.1126/science.6270791 | 107,984,884 | Mid-aged rats were either adrenalectomized and chronically maintained, or left intact and treated daily for a 9- to 10-month period with a potent analog of the peptide adrenocorticotropin (residues 4 to 9), which has some stimulant properties, or with the neural stimulant pentylenetetrazole. All three treatments reduce... | 10.1038/nrn1555 | A pioneering study, which showed that mid-life exposure to glucocorticoids contributes to the deleterious effects on brain structure and function that accompany the ageing process in rats. |
10.1111/j.1471-4159.1992.tb08477.x | 45,404,349 | Abstract: Intraventricular infusions of anti‐neural cell adhesion molecule (anti‐NCAM) are demonstrated to inhibit consolidation of a passive avoidance response when administered in the 6‐8‐h posttraining period. Anti‐NCAM was ineffective when administered during training or at any other time up to 10 h thereafter, and... | 10.1038/nrn1555 | This was the first study in which pharmacological interference with NCAM function was found to inhibit memory consolidation processes, implicating NCAM in the mechanisms that mediate the transfer of information into long-term memory. |
10.1046/j.1460-9568.1999.00593.x | 41,295,896 | Abstract The highly polysialylated neural cell adhesion molecule (PSA‐NCAM) is one of the most promising molecules that contributes to plasticity in the central nervous system. We evaluated PSA‐NCAM immunoreactivity in the hippocampal formation of Alzheimer's disease (AD) patients. We found significant increases over c... | 10.1038/nrn1555 | This report shows evidence in humans that implicates excessive concentrations of PSA–NCAM in neural damage and cognitive dysfunction. |
10.1046/j.0953-816x.2001.01685.x | 58,579,362 | Abstract Adrenal corticosteroids (CORT) have a profound effect on the function of the hippocampus. This is mediated in a coordinated manner by mineralocorticoid (MR) and glucocorticoid receptors (GR) via activation or repression of target genes. The aim of this study was to identify, using serial analysis of gene expre... | 10.1038/nrn1555 | This study shows that many hippocampal genes are regulated by corticosteroid receptors. It also implicates cell adhesion molecules as targets of glucocorticoid receptor function. |
10.1046/j.1460-9568.1998.00316.x | 58,527,471 | Abstract The gyrus dentatus is one of the few areas of the brain that continues to produce neurons after birth. The newborn cells differentiate into granule cells which project axons to their postsynaptic targets. This step is accompanied by the transient expression of the polysialylated isoforms of neuronal cell adhes... | 10.1038/nrn1555 | This paper showed for the first time that the hippocampal expression of PSA–NCAM is under the regulatory control of glucocorticoids. |
10.1126/science.1226339 | 104,292,993 | Transcription Around the Clock The biological clock that controls daily rhythms in mammalian physiology and behavior is thought to be regulated in large part by transcriptional events (see the Perspective by Doherty and Kay ). Koike et al. (p. 349 ; published online 30 August) produced a comprehensive analysis of these... | 10.1038/nsmb.3324 | This work mapped the circadian cistromes of many clock factors |
10.1101/gad.228536.113 | 83,384,616 | The mammalian circadian clock relies on the master genes CLOCK and BMAL1 to drive rhythmic gene expression and regulate biological functions under circadian control. Here we show that rhythmic CLOCK:BMAL1 DNA binding promotes rhythmic chromatin opening. Mechanisms include CLOCK:BMAL1 binding to nucleosomes and rhythmic... | 10.1038/nsmb.3324 | This study showed that BMAL1 and CLOCK function similarly to pioneer factors by binding to chromatin and evicting nucleosomes near E-boxes |
10.1126/science.1198125 | 62,496,189 | Circadian control of liver metabolism is mediated by cycles of recruitment of the histone deacetylase HDAC3. | 10.1038/nsmb.3324 | This study demonstrated that a clock factor recruits epigenomic machinery and consequently modifies local chromatin structure and regulates metabolic gene expression in the liver |
10.1101/gad.12.2.246 | 82,973,166 | POU transcription factors participate in cell-identity decisions during nervous system development, yet little is known about the regulatory networks controlling their expression. We report all known Drosophila POU genes require castor ( cas ) for correct CNS expression. drifter and I-POU depend on cas for full express... | 10.1038/nrn3618 | These authors were the first to identify laminar gene expression of Hb, Pdm and Cas in the late embryonic D. melanogaster CNS; this work set the stage for the functional characterization of temporal identity in embryonic neuroblasts by Isshiki et al . (reference 5). |
10.1126/science.1223616 | 20,370,106 | Generating the Cortex During development of the cerebral cortex, radial glial neural progenitor cells generate layer-specific subtypes of excitatory neurons in a defined temporal sequence, in which deep layers are formed before upper layers. The prevailing model for cortical neurogenesis over the last 20 years has been... | 10.1038/nrn3618 | This study suggests that a subset of cortical progenitors is fate-restricted to produce the upper-cortical-layer neurons from the beginning of neurogenesis. |
10.1073/pnas.1216793109 | 84,482,064 | Neurons within each layer in the mammalian cortex have stereotypic projections. Four genes— Fezf2, Ctip2, Tbr1 , and Satb2 —regulate these projection identities. These genes also interact with each other, and it is unclear how these interactions shape the final projection identity. Here we show, by generating double mu... | 10.1038/nrn3618 | This is an important work showing the complex interplay between cell-fate determinants that is required to establish correct cortical-neuron identity. |
10.1073/pnas.1215707110 | 103,923,093 | During cerebral cortex development, a series of projection neuron types is generated in a fixed temporal order. In Drosophila neuroblasts, the transcription factor hunchback encodes first-born identity within neural lineages. One of its mammalian homologs, Ikaros, was recently reported to play an equivalent role in ret... | 10.1038/nrn3618 | An important study showing that Ikaros acts as an early temporal-identity factor in the cortex but does not seem to extend the neurogenic competence window. The results shown here are remarkably similar to those observed for the Ikaros orthologue, Hb, in D. melanogaster neuroblasts. |
10.1242/dev.127.13.2863 | 62,570,795 | During early stages of cerebral cortical development, progenitor cells in the ventricular zone are multipotent, producing neurons of many layers over successive cell divisions. The laminar fate of their progeny depends on environmental cues to which the cells respond prior to mitosis. By the end of neurogenesis, howeve... | 10.1038/nrn3618 | This pioneering work used heterochronic transplantation to show that over time, mammalian cortical progenitors lose competence to specify early-born cortical laminar fates. |
10.1126/science.254.5029.282 | 82,984,284 | The neocortex is patterned in layers of neurons that are generated in an orderly sequence during development. This correlation between cell birthday and laminar fate prompted an examination of how neuronal phenotypes are determined in the developing cortex. At various times after labeling with [3H]thymidine, embryonic ... | 10.1038/nrn3618 | A pioneering work showing that progenitor competence to respond to environmental cues and produce specific cortical laminar fates is dependent on the cell cycle. |
10.1242/dev.126.3.555 | 38,274,163 | The seven major classes of cells of the vertebrate neural retina are generated from a pool of multipotent progenitor cells. Recent studies suggest a model of retinal development in which both the progenitor cells and the environment change over time (Cepko, C. L., Austin, C. P., Yang, X., Alexiades, M. and Ezzeddine, D... | 10.1038/nrn3618 | This is one of the first papers to show that mammalian retinal progenitors have limited competence to specify distinct cell fates. |
10.1242/dev.01912 | 83,248,192 | DNA methylation is a major epigenetic factor that has been postulated to regulate cell lineage differentiation. We report here that conditional gene deletion of the maintenance DNA methyltransferase I (Dnmt1) in neural progenitor cells (NPCs) results in DNA hypomethylation and precocious astroglial differentiation. The... | 10.1038/nrn3618 | An important paper showing that the neurogenesis-to-gliogenesis switch during mammalian development requires epigenetic changes in the progenitors. |
10.4049/jimmunol.165.11.6576 | 78,914,991 | Abstract Multiple sclerosis (MS) is a common and severe neurological disorder associated with an autoimmune response directed against myelin components within the CNS. Lymphocyte activation, extravasation, and recruitment, as well as effector function, involves the turning on and off of a number of genes, thus triggeri... | 10.1038/nrn784 | An analysis of cytokine expression in the lesions of patients with MS. |
10.1084/jem.194.5.669 | 81,574,264 | Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) characterized by plaques of infiltrating CD4+ and CD8+ T cells. Studies of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, focus on the contribution of CD4+ myelin-specific T cells. The role of CD8+ mye... | 10.1038/nrn784 | References 51 and 52 are the first reports on the potency of CD8 + T cells to induce EAE. |
10.1111/j.1750-3639.2001.tb00384.x | 38,412,248 | Viral induced demyelination, in both humans and rodent models, has provided unique insights into the cell biology of oligodendroglia, their complex cell‐cell interactions and mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections in which no infectious virus is re... | 10.1038/nrn784 | An excellent review on viral-induced demyelination in humans and animal models. |
10.4049/jimmunol.164.5.2782 | 82,592,867 | Abstract The accumulation of B lymphocyte clones in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and patients with other neurological disorders was investigated using PCR technologies. Oligoclonal B cell accumulations were detected in 10 of 10 MS patients, but only in 3 of 10 of the patients w... | 10.1038/nrn784 | References 86–88 established the occurrence of clonal expansion of B cells in the lesion and CSF of patients with MS. |
10.1084/jem.189.5.865 | 20,832,205 | Brain-derived neurotrophic factor (BDNF) has potent effects on neuronal survival and plasticity during development and after injury. In the nervous system, neurons are considered the major cellular source of BDNF. We demonstrate here that in addition, activated human T cells, B cells, and monocytes secrete bioactive BD... | 10.1038/nrn784 | The first report on the potential of myelin-specific T cells to secrete neurotrophins. |
10.4049/jimmunol.167.10.6009 | 28,999,415 | Abstract The presence of increased IgG in the brains of humans with infectious and inflammatory CNS diseases of unknown etiology such as multiple sclerosis may be a clue to the cause of disease. For example, the intrathecally synthesized oligoclonal bands in diseases such as subacute sclerosing panencephalitis (SSPE) o... | 10.1038/nrn784 | Successful identification of protein specificity of recombinantly expressed antibodies from the CNS of a patient with subacute sclerosing panencephalitis. |
10.1126/science.1062960 | 28,062,712 | Multiple sclerosis is a demyelinating disease, characterized by inflammation in the brain and spinal cord, possibly due to autoimmunity. Large-scale sequencing of cDNA libraries, derived from plaques dissected from brains of patients with multiple sclerosis (MS), indicated an abundance of transcripts for osteopontin (O... | 10.1038/nrn784 | A study of gene expression in MS lesions using a large-scale sequencing approach that was complemented by experiments in knockout animals. |
10.4049/jimmunol.161.2.692 | 139,057,476 | Abstract The intrathecal Ab response to Ag introduced into the normal brain has not been fully explored. Involvement of Ag-specific, peripheral B cells in an intrathecal response was studied using a normal rat model of Ag infusion through an indwelling cannula into defined brain sites, while maintaining a functionally ... | 10.1038/nrn784 | A study of the humoral immune response after administration of antigen in the CNS. |
10.1126/science.1089662 | 83,375,608 | Brains perform with remarkable efficiency, are capable of prodigious computation, and are marvels of communication. We are beginning to understand some of the geometric, biophysical, and energy constraints that have governed the evolution of cortical networks. To operate efficiently within these constraints, nature has... | 10.1038/nrn.2017.149 | This is an early (pre-connectomics) account that highlights the importance of economy and efficiency in network communication. |
10.1063/1.4980099 | 19,013,122 | Intrinsic brain activity is characterized by highly organized co-activations between different regions, forming clustered spatial patterns referred to as resting-state networks. The observed co-activation patterns are sustained by the intricate fabric of millions of interconnected neurons constituting the brain's wirin... | 10.1038/nrn.2017.149 | This paper introduces a measure that quantifies the propensity of two nodes to dynamically correlate, given the structural connectivity patterns that constrain the spread of information. |
10.1126/science.aab0551 | 104,018,719 | Signal flow during sensorimotor choices Little is known about the flow of task signals across the brain. Siegel et al. simultaneously recorded from multiple units in the sensory, parietal, prefrontal, and motor cortex while monkeys were cued to perform one among two possible simple tasks. The proportion of neurons codi... | 10.1038/nrn.2017.149 | This paper exemplifies how empirical studies can trace complex patterns of information flow in brain networks, for example between the frontal cortex and posterior cortex. |
10.1073/pnas.1616361113 | 38,248,518 | One challenge in contemporary neuroscience is to achieve an integrated understanding of the large-scale brain-wide interactions, particularly the spatiotemporal patterns of neural activity that give rise to functions and behavior. At present, little is known about the spatiotemporal properties of long-range neuronal ne... | 10.1038/nrn.2017.149 | This study demonstrates that long-range interactions in large-scale brain networks are governed by low-frequency activity. |
10.1098/rsif.2014.0881 | 81,716,741 | The structure of complex networks has attracted much attention in recent years. It has been noted that many real-world examples of networked systems share a set of common architectural features. This raises important questions about their origin, for example whether such network attributes reflect common design princip... | 10.1038/nrn.2017.149 | Combining concepts from evolutionary biology and network science, this article lays out the steps to conduct a network morphospace analysis, highlighting the potential of this framework to uncover the design rules and constraints that drive and shape the topology of a network. |
10.1523/jneurosci.2177-15.2016 | 82,905,864 | The performance of complex networks, like the brain, depends on how effectively their elements communicate. Despite the importance of communication, it is virtually unknown how information is transferred in local cortical networks, consisting of hundreds of closely spaced neurons. To address this, it is important to re... | 10.1038/nrn.2017.149 | This is a study of the network topology of directed functional interactions between neurons recorded at high temporal resolution. |
10.1084/jem.20070304 | 38,251,989 | Cerebrovascular dysfunction contributes to the pathology and progression of Alzheimer's disease (AD), but the mechanisms are not completely understood. Using transgenic mouse models of AD (TgCRND8, PDAPP, and Tg2576), we evaluated blood–brain barrier damage and the role of fibrin and fibrinolysis in the progression of ... | 10.1038/nrn3114 | A study showing BBB breakdown in models of Alzheimer's disease. |
10.1073/pnas.0608251104 | 104,325,615 | Cerebral angiopathy contributes to cognitive decline and dementia in Alzheimer's disease (AD) through cerebral blood flow (CBF) reductions and dysregulation. We report vascular smooth muscle cells (VSMC) in small pial and intracerebral arteries, which are critical for CBF regulation, express in AD high levels of serum ... | 10.1038/nrn3114 | A study showing that elevated levels of myocardin and serum response factor lead to a hypercontractile phenotype of brain arteries in Alzheimer's disease. |
10.1126/science.1194516 | 80,294,455 | Infectious Amyloid? Patients with Alzheimer's disease have characteristic lesions in the brains associated with masses of polymerized protein called β-amyloid. Recently, evidence from mouse models of Alzheimer's disease shows that brain extracts containing β-amyloid can “infect” otherwise healthy animals when injected ... | 10.1038/nrn3114 | A study showing that peripheral amyloid-β contributes to the development of cerebral β-amyloidosis in a mouse model of Alzheimer's disease. |
10.1126/science.1067568 | 125,254,979 | The deposition of amyloid-β (Aβ) peptides into amyloid plaques precedes the cognitive dysfunction of Alzheimer's disease (AD) by years. Biomarkers indicative of brain amyloid burden could be useful for identifying individuals at high risk for developing AD. As in AD in humans, baseline plasma Aβ levels in a transgenic ... | 10.1038/nrn3114 | A study showing that a circulating anti-amyloid-β antibody promotes efflux of this peptide from brain to blood. |
10.1126/science.1197623 | 20,845,807 | Alzheimer’s disease is associated with reduced β-amyloid clearance from the brain | 10.1038/nrn3114 | An important study demonstrating faulty amyloid-β clearance from the brain in patients with Alzheimer's disease. |
10.1126/science.1123511 | 20,833,246 | Dominant mutations in superoxide dismutase cause amyotrophic lateral sclerosis (ALS), a progressive paralytic disease characterized by loss of motor neurons. With the use of mice carrying a deletable mutant gene, expression within motor neurons was shown to be a primary determinant of disease onset and of an early phas... | 10.1038/nrn3114 | A study demonstrating that the toxicity conferred by an ALS-linked SOD1 mutant to microglia determines the lifespan of mice with an ALS-like disease. |
10.1152/ajpregu.00390.2012 | 123,072,313 | Insulin has long been hypothesized to cause sodium retention, potentially of enough magnitude to contribute to hypertension in obesity, metabolic syndrome, and Type II diabetes. There is an abundance of supportive evidence from correlational analyses in humans, acute insulin infusion studies in humans and animals, and ... | 10.1038/nrneph.2016.145 | This review unravels the controversy regarding the role of insulin in sodium transport in vivo |
10.1523/jneurosci.08-04-01411.1988 | 102,227,579 | Simultaneous intracellular recordings were obtained from stratum lacunosum-moleculare (L-M) interneurons and CA1 cells, and their local circuit synaptic interactions were examined. Synaptic interactions with pyramidal cells were evaluated in both intrasomatic and intradendritic pyramidal cell recordings. Stimulation of... | 10.1038/nrn3969 | An image in this paper may be the first of a filled NGF cell recorded in the CA1 stratum lacunosum moleculare. |
10.1523/jneurosci.5123-09.2010 | 103,216,807 | GABAergic interneurons critically regulate cortical computation through exquisite spatiotemporal control over excitatory networks. Precision of this inhibitory control requires a remarkable diversity within interneuron populations that is largely specified during embryogenesis. Although interneurons expressing the neur... | 10.1038/nrn3969 | This study shows that unlike cortical NGF cells which originate within the caudal ganglionic eminence, hippocampal NGF have their origins in both the medial and caudal ganglionic eminences. |
10.1523/jneurosci.1407-14.2014 | 104,150,875 | Cajal-Retzius cells orchestrate the development of cortical circuits by secreting the glycoprotein reelin. However, their computational functions are still unknown. In fact, the nature of their postsynaptic targets, major neurotransmitter released, as well as the class of postsynaptic receptors activated by their firin... | 10.1038/nrn3969 | This study shows a novel monosynaptic connection between reelin-positive Cajal–Retzius cells and NGF cells within the CA1 hippocampus. |
10.1073/pnas.0707204104 | 38,488,956 | Phasic (synaptic) and tonic (extrasynaptic) inhibition represent the two most fundamental forms of GABA A receptor-mediated transmission. Inhibitory postsynaptic currents (IPSCs) generated by GABA A receptors are typically extremely rapid synaptic events that do not last beyond a few milliseconds. Although unusually sl... | 10.1038/nrn3969 | This study shows that slow IPSCs generated by NGF cells in the cortex have characteristics of spillover-mediated transmission. |
10.1523/jneurosci.2727-09.2009 | 123,584,946 | Adult neurogenesis is the multistage process of generating neurons from adult neural stem cells. Accumulating evidence indicates that GABAergic depolarization is an important regulator of this process. Here, we examined GABAergic signaling to newly generated granule cells (GCs) of the adult mouse dentate gyrus. We show... | 10.1038/nrn3969 | This study shows that GABA A receptor-mediated synaptic signaling to adult-born neurons has characteristics of spillover-mediated transmission. |
10.1523/jneurosci.0781-13.2013 | 60,841,776 | Neural activity enhances adult neurogenesis, enabling experience to influence the construction of new circuits. GABA A receptor-mediated depolarization of newborn neurons in the adult and developing brain promotes glutamatergic synaptic integration since chronic reduction of GABA depolarization impairs morphological ma... | 10.1038/nrn3969 | This study shows that slow synaptic GABA signalling to adult born neurons provides depolarization needed for AMPA-receptor incorporation at silent synapses. |
10.1126/science.2475909 | 122,962,202 | During the development of the nervous system, growing axons must traverse considerable distances to find their targets. In insects, this problem is solved in part by pioneer neurons, which lay down the first axonal pathways when distances are at a minimum. Here the existence of a similar kind of neuron in the developin... | 10.1038/nrn1075 | The first detailed description of the pioneering projections from subplate to the internal capsule. |
10.1523/jneurosci.16-10-03219.1996 | 42,606,533 | In the nervous system of many species, growing axons associate transiently with cellular groupings along their path. Whether this mechanism applies to the development of corticothalamic and thalamocortical projections is unknown. Using carbocyanine dyes, we studied the early growth of both corticofugal and thalamocorti... | 10.1038/nrn1075 | The first description of the guidepost cells situated in the internal capsule with early dorsal thalamic projections. |
10.1242/dev.124.24.5063 | 20,881,368 | An intermediate target for axons leaving the cerebral cortex in embryonic mammals is the ganglionic eminence (GE), the embryonic precursor of the basal ganglia. The cues that direct these axons over the initial portion of their trajectory are not well understood, but could include both short-range and long-range attrac... | 10.1038/nrn1075 | The first study indicating the role of netrin 1 in the development of early cortical connectivity. |
10.1242/dev.00166 | 16,758,742 | The prevailing model to explain the formation of topographic projections in the nervous system stipulates that this process is governed by information located within the projecting and targeted structures. In mammals, different thalamic nuclei establish highly ordered projections with specific neocortical domains and t... | 10.1038/nrn1075 | This study supports the idea that early thalamic targeting in the cortex depends on signals within the ventral telencephalon and that it might be independent from early cortical gene expression. |
10.1126/science.285.5429.906 | 40,655,167 | There is a long-standing controversy regarding the mechanisms that generate the functional subdivisions of the cerebral neocortex. One model proposes that thalamic axonal input specifies these subdivisions; the competing model postulates that patterning mechanisms intrinsic to the dorsal telencephalon generate neocorti... | 10.1038/nrn1075 | References 50 and 51 provided the first evidence indicating that the early cortical gene expression pattern is independent of embryonic thalamic input. |
10.1242/dev.126.9.1903 | 125,326,449 | We have analyzed the pathfinding of thalamocortical axons (TCAs) from dorsal thalamus to neocortex in relation to specific cell domains in the forebrain of wild-type and Mash-1-deficient mice. In wild-type mice, we identified four cell domains that constitute the proximal part of the TCA pathway. These domains are dist... | 10.1038/nrn1075 | This study provides strong support for the early guiding role of the internal capsule cells and their projections in the early development of thalamic projections. |
10.1002/cne.10219 | 123,107,295 | Abstract During development, cortical areas establish precise reciprocal projections with corresponding thalamic nuclei. Pioneer axons from the cortex and thalamus first meet in the intermediate zone of the subcortical telencephalon (subpallium). Their close interactions in the subpallium suggest that they may use each... | 10.1038/nrn1075 | The experiments of this study indicate that an interaction between early corticofugal and thalamocortical projections is necessary for the correct development of both sets of fibres. |
10.1242/dev.127.23.5167 | 19,026,330 | The transcription factor Pax6 is widely expressed throughout the developing nervous system, including most alar regions of the newly formed murine diencephalon. Later in embryogenesis its diencephalic expression becomes more restricted. It persists in the developing anterior thalamus (conventionally termed “ventral” th... | 10.1038/nrn1075 | Using an elegant co-culture essay, this study provides evidence that thalamic cells are directly influenced by the lack of Pax6 , which might contribute to the pathfinding defects of early thalamocortical axons. |
10.1126/science.281.5376.559 | 19,215,199 | Connections in the developing nervous system are thought to be formed initially by an activity-independent process of axon pathfinding and target selection and subsequently refined by neural activity. Blockade of sodium action potentials by intracranial infusion of tetrodotoxin in cats during the early period when axon... | 10.1038/nrn1075 | This study shows that blocking action potentials during early stages of development in the occipital cortex disrupts the entry and areal targeting of thalamic projections. |
10.1046/j.0953-816x.2001.01554.x | 38,655,005 | Abstract The six layered cerebral cortex derives from cells that divide in the ventricular zone and migrate to their final destination in the cortical plate (future cortex). In the mouse, cortical layer III and IV neurons undergo their final mitotic division at around E16, at which time thalamic axons are beginning to ... | 10.1038/nrn1075 | This study demonstrates that thalamic input stimulates cortical neural migration. |
10.1111/j.1471-4159.1993.tb09796.x | 83,131,989 | Abstract— Recent studies have identified at least two homologous mitogen‐activated protein (MAP) kinases that are activated by phosphorylation of both tyrosine and threonine residues by an activator kinase. To help define the role of these MAP kinases in neuronal signalling, we have used primary cultures derived from f... | 10.1038/nrn1346 | The first report of ERK activation in response to glutamate receptor stimulation and synaptic activity. |
10.1126/science.1059075 | 103,212,700 | Experience-dependent plasticity in the developing visual cortex depends on electrical activity and molecular signals involved in stabilization or removal of inputs. Extracellular signal–regulated kinase 1,2 (also called p42/44 mitogen-activated protein kinase) activation in the cortex is regulated by both factors. We s... | 10.1038/nrn1346 | The first demonstration that ERK is required for cortical plasticity. |
10.1073/pnas.051634198 | 123,925,395 | The cAMP-responsive element binding protein (CREB), a key regulator of gene expression, is activated by phosphorylation on Ser-133. Several different protein kinases possess the capability of driving this phosphorylation, making it a point of potential convergence for multiple intracellular signaling cascades. Previous... | 10.1038/nrn1346 | This study, together with reference 73, reports that prolonged CREB phosphorylation is sensitive to MEK inhibitors in cultured neurons. |
10.1073/pnas.87.19.7668 | 18,657,947 | We have quantitatively analyzed the relationship between translational efficiency and the mRNA secondary structure in the initiation region. The stability of a defined hairpin structure containing a ribosome binding site was varied over 12 kcal/mol (1 cal = 4.184 J) by site-directed mutagenesis and the effects on prote... | 10.1038/nrmicro2730 | A seminal study on the relationship between mRNA secondary structure and translation efficiency. |
10.1073/pnas.92.2.507 | 60,572,954 | After the start of transcription, the 5' ends of eukaryotic mRNA molecules are modified by the addition of a guanylyl residue to form a cap structure, G(5')ppp(5')N. The guanylyltransferase (GTP:mRNA guanylyltransferase, EC 2.7.7.50) reaction responsible for cap formation usually proceeds via a covalent enzyme-GMP inte... | 10.1038/nrmicro2675 | The discovery of the unconventional RNA-capping pathway of alphaviruses, in which guanine-N7 methylation of GTP precedes m 7 GMP transfer onto the putative GTase, nsP1. |
10.1073/pnas.0807211105 | 79,642,183 | The minus strand and ambisense segmented RNA viruses include multiple important human pathogens and are divided into three families, the Orthomyxoviridae , the Bunyaviridae , and the Arenaviridae . These viruses all initiate viral transcription through the process of “cap-snatching,” which involves the acquisition of c... | 10.1038/nrmicro2675 | An article that casts light on how N protein binds preferentially to capped mRNAs, stores and protects these mRNAs in P-bodies, and potentially takes an active role in cap acquisition. |
10.1126/science.1132998 | 104,095,857 | Double-stranded RNA (dsRNA) produced during viral replication is believed to be the critical trigger for activation of antiviral immunity mediated by the RNA helicase enzymes retinoic acid–inducible gene I (RIG-I) and melanoma differentiation–associated gene 5 (MDA5). We showed that influenza A virus infection does not... | 10.1038/nrmicro2675 | The 5′-triphosphate of viral RNA is identified as a major component in the RIG-I-mediated host innate immune response. |
10.1073/pnas.96.7.4034 | 20,006,246 | It is now accepted that hippocampal lesions impair episodic memory. However, the precise functional role of the hippocampus in episodic memory remains elusive. Recent functional imaging data implicate the hippocampus in processing novelty, a finding supported by human in vivo recordings and event-related potential stud... | 10.1038/nrn3785 | The first experimental demonstration, using fMRI, of a double dissociation in anterior versus posterior human hippocampal responses. |
10.1523/jneurosci.13-09-03916.1993 | 125,071,488 | The hippocampus plays an essential role in spatial learning. To investigate whether the whole structure is equally important, we compared the effects of variously sized and localized hippocampal aspiration lesions on spatial learning in a Morris water maze. The volume of all hippocampal lesions was determined. Dorsal h... | 10.1038/nrn3785 | This study, along with that reported in reference 22, made an important advance in localizing rodent spatial function predominantly to the dorsal hippocampus. By controlling the size and locus of hippocampal lesions, this work demonstrated that restricted dorsal hippocampal lesions, but not similarly sized ventral lesi... |
10.1126/science.272.5267.1484 | 19,080,805 | The hippocampus has two major outputs: multisynaptic pathways to the cerebral cortex and a massive descending projection directly to the lateral septal part of the basal ganglia. Here it is shown that the descending output is organized in such a way that different hippocampal regions map in an orderly way onto hypothal... | 10.1038/nrn3785 | A beautiful demonstration of topographical hippocampal connectivity with subcortical areas, this is one of the earliest studies to imply that the hippocampal long axis could comprise multiple domains as opposed to a ventral–dorsal dichotomy. |
10.1126/science.1157086 | 107,325,584 | To determine how spatial scale is represented in the pyramidal cell population of the hippocampus, we recorded neural activity at multiple longitudinal levels of this brain area while rats ran back and forth on an 18-meter-long linear track. CA3 cells had well-defined place fields at all levels. The scale of representa... | 10.1038/nrn3785 | The first evidence for a gradient of function in the rodent hippocampal long axis. A gradual increase in place field size from the dorsal to ventral hippocampus also indicates that the ventral hippocampus may subserve similar spatial processing functions as the dorsal hippocampus, but at a larger spatial scale. |
10.1126/science.1077775 | 101,152,234 | The medial temporal lobe (MTL) is critical in forming new memories, but how subregions within the MTL carry out encoding and retrieval processes in humans is unknown. Using new high-resolution functional magnetic resonance imaging (fMRI) acquisition and analysis methods, we identified mnemonic properties of different s... | 10.1038/nrn3785 | This important methodological advance in human MRI of the hippocampus was the forerunner for now a large number of high-resolution hippocampal fMRI studies that localize activity to different hippocampal subregions. |
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