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10.1126/science.2326637
102,343,882
The organization of the visual cortex has been considered to be highly stable in adult mammals. However, 5° to 10° lesions of the retina in the contralateral eye markedly altered the systematic representations of the retina in primary and secondary visual cortex when matched inputs from the ipsilateral eye were also re...
10.1038/nrn2741
The first report suggesting that adult V1 reorganizes following retinal damage and that such reorganization may be important for normal adjustments of sensory systems to environmental contingencies.
10.1152/jn.00692.2001
62,274,273
Information is integrated across the visual field to transform local features into a global percept. We now know that V1 neurons provide more spatial integration than originally thought due to the existence of their nonclassical inhibitory surrounds. To understand spatial integration in the visual cortex, we have studi...
10.1038/nrn2741
A thorough attempt to quantify and model the properties of the V1 receptive field, with a particular emphasis on understanding size and sensitivity to contrast.
10.1073/pnas.96.7.3922
41,742,811
Amyloid β peptide (Aβ), the principal proteinaceous component of amyloid plaques in brains of Alzheimer’s disease patients, is derived by proteolytic cleavage of the amyloid precursor protein (APP). Proteolytic cleavage of APP by a putative α-secretase within the Aβ sequence precludes the formation of the amyloidogenic...
10.1038/nrn785
References 33–37 show that α-secretase cleavage is a physiological, regulated cleavage of APP, and that TACE and other members of the ADAM superfamily are good candidates for this enzymatic activity.
10.1073/pnas.110126897
20,782,678
γ-Secretase is a membrane-associated protease that cleaves within the transmembrane region of amyloid precursor protein to generate the C termini of the two Aβ peptide isoforms, Aβ40 and Aβ42. Here we report the detergent solubilization and partial characterization of γ-secretase. The activity of solubilized γ-secretas...
10.1038/nrn785
References 75–78 describe the discovery that PS1 is part of a multimeric, high-molecular-weight protein complex.
10.1068/p5563
61,290,212
Object recognition is a crucial component of both visual and auditory perception. It is also critical for olfaction. Most odours are composed of 10s or 100s of volatile components, yet they are perceived as unitary perceptual events against a continually shifting olfactory background (ie figure—ground segregation). We ...
10.1038/nrn2883
Drawing from psychological studies in humans and electrophysiological studies in rodents, this review provides a thoughtful account of odour object perception.
10.1002/cne.903460306
67,620,876
Abstract The connections between the olfactory bulb, primary olfactory cortex, and olfactory related areas of the orbital cortex were defined in macaque monkeys with a combination of anterograde and retrograde axonal tracers and electrophysiological recording. Anterograde tracers placed into the olfactory bulb labeled ...
10.1038/nrn2883
tour de force study combining anatomical tracers and electrophysiological recordings to delineate olfactory connectivity in primate olfactory cortex.
10.1152/jn.00133.2003
38,491,274
Current views of odorant discrimination by the mammalian olfactory system suggest that the piriform cortex serves as a site of odor object synthesis. Given the enormous number of odorant feature combinations possible in nature, however, it seems unlikely that cortical synthetic receptive fields (RFs) are innate but rat...
10.1038/nrn2883
References 117, 147 and 148 comprise an important set of studies establishing that odour configural processing occurs in rodent anterior piriform cortex as a consequence of olfactory habituation; a non-associative form of perceptual learning. Insights from this study paved the way for a similar but human-based study th...
10.1073/pnas.0504984102
16,673,654
Fragile X syndrome, the most frequent form of hereditary mental retardation, is due to a mutation of the fragile X mental retardation 1 ( FMR1 ) gene on the X chromosome. Like fragile X patients, FMR1 -knockout ( FMR1 -KO) mice lack the normal fragile X mental retardation protein (FMRP) and show both cognitive alterati...
10.1038/nrn1970
The first study to show that enrichment results in beneficial effects on both brain and behaviour in a mouse model of fragile X syndrome.
10.1101/gad.12.21.3394
81,301,906
Inductive factors are known to direct the regional differentiation of the vertebrate central nervous system (CNS) but their role in the specification of individual neuronal cell types is less clear. We have examined the function of GDF7, a BMP family member expressed selectively by roof plate cells, in the generation o...
10.1038/nrn1073
This paper provides the only genetic evidence to date that a BMP family member is necessary for dorsal neural tube patterning.
10.1101/gad.982802
38,571,643
Trigeminal nuclei and the dorsal spinal cord are first-order relay stations for processing somatic sensory information such as touch, pain, and temperature. The origins and development of these neurons are poorly understood. Here we show that relay somatic sensory neurons and D2/D4 dorsal interneurons likely derive fro...
10.1038/nrn1073
A detailed genetic analysis of how local interactions control cell fate in the neural tube.
10.1126/science.1192850
57,266,976
Mr. Blebby Vibrio parahaemolyticus , an important cause of contaminated fish-associated food poisoning, kills infected host cells within hours, using three sequential mechanisms: autophagy, cell rounding, and cell lysis. Broberg et al. (p. 1660 , published online 19 August) now describe a molecular mechanism of a bacte...
10.1038/nrmicro2602
Demonstrates a mechanism of action for an effector from V. parahaemolyticus that manipulates plasma membrane integrity via PI phosphatase activity.
10.1126/science.1166382
84,387,472
The Vibrio parahaemolyticus type III effector VopS is implicated in cell rounding and the collapse of the actin cytoskeleton by inhibiting Rho guanosine triphosphatases (GTPases). We found that VopS could act to covalently modify a conserved threonine residue on Rho, Rac, and Cdc42 with adenosine 5′-monophosphate (AMP)...
10.1038/nrmicro2602
Describes a bacterial effector that catalyses a novel post-translational modification, AMPylation, to modify RHO-family GTPases and disrupt the actin cytoskeleton.
10.1126/science.1130197
103,752,020
We used functional magnetic resonance imaging to demonstrate preserved conscious awareness in a patient fulfilling the criteria for a diagnosis of vegetative state. When asked to imagine playing tennis or moving around her home, the patient activated predicted cortical areas in a manner indistinguishable from that of h...
10.1038/nrn.2016.22
The first study to use fMRI to infer consciousness in a behaviourally non-responsive patient in a vegetative state.
10.1126/science.1117256
38,402,523
When we fall asleep, consciousness fades yet the brain remains active. Why is this so? To investigate whether changes in cortical information transmission play a role, we used transcranial magnetic stimulation together with high-density electroencephalography and asked how the activation of one cortical area (the premo...
10.1038/nrn.2016.22
The first study to use TMS and EEG to measure the breakdown of causal integration and differentiation during slow wave sleep.
10.1146/annurev-neuro-062012-170339
123,319,755
Significant advances have been made in the behavioral assessment and clinical management of disorders of consciousness (DOC). In addition, functional neuroimaging paradigms are now available to help assess consciousness levels in this challenging patient population. The success of these neuroimaging approaches as diagn...
10.1038/nrn.2016.22
A comprehensive review of clinical and neuroimaging aspects of disorders of consciousness.
10.1098/rstb.1998.0333
86,243,960
Figures that can be seen in more than one way are invaluable tools for the study of the neural basis of visual awareness, because such stimuli permit the dissociation of the neural responses that underlie what we perceive at any given time from those forming the sensory representation of a visual pattern. To study the ...
10.1038/nrn.2016.22
A review of Logothetis' classic single-neuron studies in the visual cortex of monkeys undergoing binocular competition.
10.1126/science.1169896
85,554,859
Consciousness and Intention Where in the brain are our intentions formed and how do we become aware of these intentions? Desmurget et al. (p. 811 ; see the Perspective by Haggard ) investigated the effect of direct cortical stimulation of parietal and premotor regions in patients undergoing brain surgery for tumor remo...
10.1038/nrn.2016.22
A neurosurgical account reporting that direct electrical stimulation of the posterior parietal cortex causes a conscious intention to move without an actual motor response.
10.1126/science.1254126
83,012,302
Top-down modulation of sensory processing allows the animal to select inputs most relevant to current tasks. We found that the cingulate (Cg) region of the mouse frontal cortex powerfully influences sensory processing in the primary visual cortex (V1) through long-range projections that activate local γ-aminobutyric ac...
10.1038/nrn.2016.22
A study analysing the circuits mediating top-down visual attention in transgenic mice using optogenetics.
10.1126/scitranslmed.3006294
62,268,771
A theory-derived index of consciousness, which quantifies the complexity of the brain’s response to a stimulus, measures the level of consciousness in awake, sleeping, anesthetized, and brain-damaged subjects.
10.1038/nrn.2016.22
The first study to use a combined TMS and EEG paradigm to quantify the level of consciousness under a variety of conditions and at the level of individual patients.
10.1177/1745691612460684
100,498,080
Understanding the division of labor between conscious processes and unconscious ones is central to our understanding of the human mind. This article proposes a simple “Yes It Can” (or YIC) principle: It argues that unconscious processes can perform the same fundamental, high-level functions that conscious processes can...
10.1038/nrn.2016.22
An edited volume describing a series of experiments that demonstrate non-conscious processing under a variety of laboratory and real-life conditions.
10.1126/science.6267699
104,151,122
A peptide with high potency and intrinsic activity for stimulating the secretion of corticotropin-like and β-endorphin-like immunoactivities by cultured anterior pituitary cells has been purified from ovine hypothalamic extracts. The primary structure of this 41-residue corticotropin- and β-endorphin-releasing factor h...
10.1038/nrn.2016.94
This is the first study to describe the discovery and characterization of CRF, which has initiated decades of research on the CRF–UCN system.
10.1126/science.6334362
62,433,916
The possibility that hypersecretion of corticotropin-releasing factor (CRF) contributes to the hyperactivity of the hypothalamo-pituitary-adrenal axis observed in patients with major depression was investigated by measuring the concentration of this peptide in cerebrospinal fluid of normal healthy volunteers and in dru...
10.1038/nrn.2016.94
This study provides the first evidence that disturbances in CRF signalling may have a role in depression.
10.1126/science.1202107
123,062,156
An imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic systems might lead to emotional disturbances.
10.1038/nrn.2016.94
In this study, the authors investigate electrophysiological and behavioural outcome measures of conditional Crfr1 inactivation in glutamatergic, GABAergic, dopaminergic and serotonergic neuronal populations to show that the effects of CRFR1-mediated signalling are cell-type specific.
10.1523/jneurosci.4196-04.2005
81,791,648
Corticotropin-releasing factor (CRF) and urocortin (Ucn I) are endogenous members among a family of CRF-related peptides that activate two different and synaptically localized G-protein-coupled receptors, CRF 1 and CRF 2 . These peptides and their receptors have been implicated in stress responses and stress with cocai...
10.1038/nrn.2016.94
This study shows that exposure to drugs of abuse alters the sensitivity and function of local UCN signalling in the LS; the CRFR2-mediated depression of LS neuronal activity induced by UCN1 is switched by chronic cocaine to facilitation (with a comparable UCN1 potency), and this switch is linked to a change from a PKA-...
10.1111/j.1471-4159.2007.05052.x
26,960,740
Abstract Endogenous expression of the corticotropin‐releasing factor type 2a receptor [CRF 2(a) ] but not CRF 2(b) and CRF 2(c) was observed in higher passage cultures of human Y79 retinoblastoma cells. Functional studies further demonstrated an increase in CRF 2(a) mRNA and protein levels with higher passage numbers (...
10.1038/nrn.2016.94
This paper indicates that desensitization and internalization processes following CRFR activation depend on the specific ligand that is bound; desensitization of CRFR2–cAMP signalling was shown to occur more rapidly and to a greater extent in response to UCN2 than to UCN3, whereas CRF is a relatively weak desensitizing...
10.1073/pnas.92.9.3893
104,201,724
Atherosclerosis, an underlying cause of myocardial infarction, stroke, and other cardiovascular diseases, consists of focal plaques characterized by cholesterol deposition, fibrosis, and inflammation. The presence of activated T lymphocytes and macrophages and high expression of HLA class II molecules are indicative of...
10.1038/nrneph.2017.51
Discovery of the cellular immune response in the atherosclerotic plaque.
10.1126/science.1990440
26,859,484
An inducible rabbit endothelial adhesion molecule that is selective for mononuclear leukocytes has been identified. This adhesion protein was expressed on the surface of activated cultured endothelium in two forms, 118 and 98 kilodaltons, the amino-terminal sequence of each being highly homologous to human VCAM-1. In d...
10.1038/nrneph.2017.51
Discovery that the leukocyte-recruiting adhesion molecule VCAM-1 is induced during atherogenesis.
10.1084/jem.20030997
27,015,240
Adaptive and innate immunity have been implicated in the pathogenesis of atherosclerosis. Given their abundance in the lesion, lipids might be targets of the atherosclerosis-associated immune response. Natural killer T (NKT) cells can recognize lipid antigens presented by CD1 molecules. We have explored the role of CD1...
10.1038/nrneph.2017.51
Study demonstrating a role of lipid-recognizing natural killer T cells in atherosclerosis.
10.1084/jem.20092243
103,349,611
Immune responses to oxidized low-density lipoprotein (oxLDL) are proposed to be important in atherosclerosis. To identify the mechanisms of recognition that govern T cell responses to LDL particles, we generated T cell hybridomas from human ApoB100 transgenic (huB100tg) mice that were immunized with human oxLDL. Surpri...
10.1038/nrneph.2017.51
Study showing that T cells recognize ApoB peptides of LDL.
10.1073/pnas.0409015102
82,990,637
The influence of the immune system on atherosclerosis involves both helper T (Th) cell and antibody responses to plaque antigens. These responses may have proatherogenic and protective effects. T-bet is a transcription factor required for Th1 differentiation and regulates the balance between Th1 and Th2 responses in in...
10.1038/nrneph.2017.51
Study showing that the T H 1 pathway is proatherogenic.
10.1126/scitranslmed.3006133
61,303,613
Adaptive immunity has a major impact on atherosclerosis, with pro- and anti-atherosclerotic effects exerted by different subpopulations of T cells. Transforming growth factor–β (TGF-β) may promote development either of anti-atherosclerotic regulatory T cells or of T helper 17 (T H 17) cells, depending on factors in the...
10.1038/nrneph.2017.51
Study of the plaque-stabilizing role of T H 17 cells.
10.1111/j.1365-2796.2010.02260.x
40,050,146
Abstract. Holmqvist ME, Wedrén S, Jacobsson LTH, Klareskog L, Nyberg F, Rantapää‐Dahlqvist S, Alfredsson L, Askling J (Institute of Environmental Medicine, Karolinska Institutet, Stockholm; Karolinska Institutet/Karolinska Hospital, Stockholm; Malmö University Hospital, Malmö; AstraZeneca R&D, Mölndal; and Umeå Uni...
10.1038/nrneph.2017.51
Study demonstrating an increased risk of cardiovascular disease in patients with rheumatoid arthritis.
10.1073/pnas.92.3.821
19,710,150
Atherosclerotic lesions contain oxidized LDL (OxLDL), immunoglobulins, and immune-competent cells. Low levels of circulating autoantibodies against malondialdehyde (MDA)-modified lysine, an epitope of OxLDL, occur in several species, and immune complexes between such autoantibodies and OxLDL are present in lesions. To ...
10.1038/nrneph.2017.51
First report of protective immunity against atherosclerosis induced by vaccination.
10.1152/ajpregu.00817.2010
120,604,127
The pattern of regional brain activation in humans during thirst associated with dehydration, increased blood osmolality, and decreased blood volume is not known. Furthermore, there is little information available about associations between activation in osmoreceptive brain regions such as the organum vasculosum of the...
10.1038/nrneph.2017.149
This human fMRI study reveals the brain regions involved in generating thirst.
10.1152/ajpregu.00869.2007
36,904,695
The pathways involved in the emotional aspects of thirst, the arousal and affect associated with the generation of thirst and the motivation to obtain satiation, have been studied but remain poorly understood. Rats were therefore injected with the neurotropic virus pseudorabies in either the insular or cingulate cortex...
10.1038/nrneph.2017.149
This anatomical study demonstrates brain regions and circuits involved in generating thirst in rats.
10.1126/science.aan6747
62,060,109
A cell type in the median preoptic nucleus integrates water intake over time and controls thirst behavior in mice.
10.1038/nrneph.2017.149
This study demonstrates that MnPO neurons encode the negative valence associated with thirst.
10.1002/ajmg.1408
123,759,605
Abstract Attention‐deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. The role of genetic factors in its etiology is strongly supported by family, adoption, and twin studies. Several investigations have reported associations between ADHD and both the 7‐repeat allele of t...
10.1038/nrn896
The first replicated report of a gene locus associated with ADHD.
10.1126/science.289.5478.457
123,914,065
Universal positive correlations between different cognitive tests motivate the concept of “general intelligence” or Spearman's g . Here the neural basis for g is investigated by means of positron emission tomography. Spatial, verbal, and perceptuo-motor tasks with high- g involvement are compared with matched low- g co...
10.1038/nrn1405
A PET study of high- g versus low- g tasks. It is notable for using brain imaging data to inform the debate about the structure of intelligence.
10.1046/j.0956-7976.2003.psci_1475.x
103,773,443
Scores on the Wechsler Intelligence Scale for Children were analyzed in a sample of 7-year-old twins from the National Collaborative Perinatal Project. A substantial proportion of the twins were raised in families living near or below the poverty level. Biometric analyses were conducted using models allowing for compon...
10.1038/nrn1405
The heritability of intelligence depends on socioeconomic status, with low heritability at low socioeconomic status, and higher heritability for high socioeconomic status.
10.1126/science.276.5321.2045
83,454,674
Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromoso...
10.1038/nrn3549
This study made the landmark discovery of SNCA mutations in PD.
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/nrn3549
This study made the landmark discovery of how the transmission of α-syn fibrils alone recapitulates human disease in wild-type animals.
10.1002/ana.23659
41,743,975
Abstract Objective: A study was undertaken to examine the neuropathological substrates of cognitive dysfunction and dementia in Parkinson disease (PD). Methods: One hundred forty patients with a clinical diagnosis of PD and either normal cognition or onset of dementia 2 or more years after motor symptoms (PDD) were stu...
10.1038/nrn3549
A large autopsy cohort involving multivariate analysis of multiple clinical, genetic and neuropathological variables that implicate Lewy body and neurite pathology as the strongest correlate of PDD.
10.1073/pnas.97.3.1125
16,753,627
Glucose transport in insulin-regulated tissues is mediated by the GLUT4 and GLUT1 transporters. Using the yeast two-hybrid system, we have cloned the sentrin-conjugating enzyme mUbc9 as a protein that interacts with the GLUT4 COOH-terminal intracellular domain. The mUbc9 enzyme was found to bind directly to GLUT4 and G...
10.1038/nrn2276
This paper was the first to show the SUMO modification of a plasma membrane protein.
10.1126/science.1122513
109,077,727
Postsynaptic differentiation of dendrites is an essential step in synapse formation. We report here a requirement for the transcription factor myocyte enhancer factor 2A (MEF2A) in the morphogenesis of postsynaptic granule neuron dendritic claws in the cerebellar cortex. A transcriptional repressor form of MEF2A that i...
10.1038/nrn2276
This paper, together with the work in reference 98, demonstrated that MEF2 transcription factors can be modified by phosphorylation, acetylation and SUMOylation. The balance between these modifications acts to control activity-dependent synapse formation.
10.1126/science.1092194
59,310,323
Huntington's disease (HD) is characterized by the accumulation of a pathogenic protein, Huntingtin (Htt), that contains an abnormal polyglutamine expansion. Here, we report that a pathogenic fragment of Htt (Httex1p) can be modified either by small ubiquitin-like modifier (SUMO)–1 or by ubiquitin on identical lysine re...
10.1038/nrn2276
This was the first study to demonstrate a mechanistic role for SUMOylation in Huntington's disease pathology.
10.1083/jcb.200807073
20,496,370
The planar cell polarity (PCP) pathway organizes the cytoskeleton and polarizes cells within embryonic tissue. We investigate the relationship between PCP signaling and cell fate determination during asymmetric division of neural progenitors (NPs) in mouse embryos. The cortex of Lp/Lp (Loop-tail) mice deficient in the ...
10.1038/nrn3525
This work shows that in mice, the looptail mutation in Vangl2 affects the mitotic spindle orientation and has an impact on cell fate determination and lamination of the cerebral cortex.
10.1126/science.1089610
102,350,281
Commissural neurons in the mammalian dorsal spinal cord send axons ventrally toward the floor plate, where they cross the midline and turn anteriorly toward the brain; a gradient of chemoattractant(s) inside the spinal cord controls this turning. In rodents, several Wnt proteins stimulate the extension of commissural a...
10.1038/nrn3525
This is the first study to show that the WNT and PCP signalling guides spinal cord commissural axons along the anterior–posterior axis after midline crossing.
10.1126/science.280.5360.69
83,368,665
The potassium channel from Streptomyces lividans is an integral membrane protein with sequence similarity to all known K + channels, particularly in the pore region. X-ray analysis with data to 3.2 angstroms reveals that four identical subunits create an inverted teepee, or cone, cradling the selectivity filter of the ...
10.1038/nrn725
The first crystallographic structure of an ion channel, revealing mechanisms by which ion selectivity is combined with high flux.
10.1126/science.280.5369.1596
38,398,771
The subunit stoichiometry of several ligand-gated ion channel receptors is still unknown. A counting method was developed to determine the number of subunits in one family of brain glutamate receptors. Successful application of this method in an HEK cell line provides evidence that ionotropic glutamate receptors share ...
10.1038/nrn725
The analysis of gating transitions in iGluR under non-desensitizing conditions revealed incremental opening of the conducting pore, consistent with independent gating by four subunits assembled as a tetramer.
10.1126/science.285.5424.73
58,564,361
The intramembrane molecular events underlying activation gating in the Streptomyces K + channel were investigated by site-directed spin-labeling methods and electron paramagnetic resonance spectroscopy. A comparison of the closed and open conformations of the channel revealed periodic changes in spin-label mobility and...
10.1038/nrn725
Electron paramagnetic resonance spectroscopic analysis allowed the identification of conformational changes associated with gating of a K + channel.
10.1073/pnas.0405968101
20,166,331
Migratory birds can use a magnetic compass for orientation during their migratory journeys covering thousands of kilometers. But how do they sense the reference direction provided by the Earth's magnetic field? Behavioral evidence and theoretical considerations have suggested that radical-pair processes in differently ...
10.1038/nrn1745
Gives molecular and neurobiological evidence that cryptochromes are expressed in the retinae of birds immediately before migratory behavior.
10.1242/jeb.205.24.3845
83,062,834
SUMMARY Magnetic compass orientation in birds has been shown to be light dependent. Results from behavioural studies indicate that magnetoreception capabilities are disrupted under light of peak wavelengths longer than 565 nm, and shifts in orientation have been observed at higher light intensities(43-44×1015 quanta s-...
10.1038/nrn1745
Reports on tests of magnetic orientation under diverse lighting environments and reviews light-dependent effects up to 2001.
10.1002/cne.10579
40,789,648
Abstract With the use of different light and electron microscopic methods, we investigated the subcellular organization of afferent trigeminal terminals in the upper beak of the homing pigeon, Columba livia , which are about 5 μm in diameter and contain superparamagnetic magnetite (SPM) crystals. The SPM nanocrystals a...
10.1038/nrn1745
Provides detailed ultrastructure of deposits of superparamagnetic magnetite crystals in the beak of a bird.
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/nrn1683
This paper describes a comprehensive database of MR- and GR-responsive gene patterns in the hippocampus.
10.1002/cne.1297
102,913,676
Abstract To determine whether exposure to fox odor alters granule neuron production, we examined proliferating cells and their progeny in the dentate gyrus of adult male rats exposed to trimethyl thiazoline, a component of fox feces. Additionally, to determine whether this effect is adrenal hormone‐mediated, we examine...
10.1038/nrn1683
This report describes how stressful experiences rapidly diminish cell proliferation by increasing adrenal hormone levels, which results in a transient decrease in the number of adult-generated immature granule neurons.
10.1126/science.2781292
56,780,848
The CA1 pyramidal neurons in the hippocampus contain a high density of adrenal corticosteroid receptors. By intracellular recording, CA1 neurons in slices from adrenalectomized rats have been found to display a markedly reduced afterhyperpolarization (that is, the hyperpolarizing phase after a brief depolarizing curren...
10.1038/nrn1683
This paper shows that glucocorticoids can reduce transmitter-evoked excitability in the hippocampus, presumably through receptor-mediated genomic actions.
10.1523/jneurosci.23-12-04850.2003
20,429,363
Glucocorticoid negative feedback in the brain controls stress, feeding, and neural-immune interactions by regulating the hypothalamic—pituitary—adrenal axis, but the mechanisms of inhibition of hypothalamic neurosecretory cells have never been elucidated. Using whole-cell patch-clamp recordings in an acute hypothalamic...
10.1038/nrn1683
This study presents evidence for rapid glucocorticoid feedback inhibition of hypothalamic hormone secretion by endocannabinoid release in the PVN.
10.1002/hipo.450020409
18,137,855
Abstract Studies have shown that peripheral levels of corticosterone correlate with the magnitudes of two well‐described physiological models of memory, long‐term potentiation (LTP) and primed burst (PB) potentiation. In the present experiments, the authors investigated the effects of experimenter‐controlled manipulati...
10.1038/nrn1683
This research shows that corticosterone exerts a concentration-dependent biphasic influence on the expression of hippocampal plasticity.
10.1073/pnas.94.25.14048
86,315,148
Evidence indicates that the modulatory effects of the adrenergic stress hormone epinephrine as well as several other neuromodulatory systems on memory storage are mediated by activation of β-adrenergic mechanisms in the amygdala. In view of our recent findings indicating that the amygdala is involved in mediating the e...
10.1038/nrn1683
This study shows that β-adrenergic activation seems to be an essential step in mediating glucocorticoid effects on memory storage and that the BLA is a locus of interaction for these two systems.
10.1523/jneurosci.16-10-03534.1996
20,791,103
We have shown previously that repeated laboratory restraint stress or daily corticosterone administration affects the structure of CA3 hippocampal neurons in rats. In the present study, we investigated the effect of repeated daily psychosocial stress on the structure of hippocampal CA3 pyramidal neurons in male tree sh...
10.1038/nrn1683
These results indicate that a naturalistic psychosocial stressor induces specific structural changes in the hippocampal neurons of subordinate male tree shrews.
10.1126/science.1083328
83,449,212
Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A rece...
10.1038/nrn1683
The authors show that the behavioural effects of chronic antidepressant use might be mediated by the stimulation of neurogenesis in the hippocampus.
10.1073/pnas.96.23.13456
57,000,900
Recent studies indicated that hyperactivity of the hypothalamo-pituitary-adrenal system is a considerable risk factor for the precipitation of affective disorders, most notably of major depression. The mechanism by which this hyperactivity eventually leads to clinical symptoms of depression is unknown. In the present a...
10.1038/nrn1683
This study shows that prolonged elevation of the corticosteroid concentration, which is a possible causative factor for depression in humans, gradually attenuates responsiveness to serotonin without necessarily decreasing serotonin-1A receptor mRNA levels in pyramidal neurons.
10.1073/pnas.93.4.1619
16,752,500
There is increasing evidence for an important role of adverse early experience on the development of major psychiatric disorders in adulthood. Corticotropin-releasing factor (CRF), an endogenous neuropeptide, is the primary physiological regulator of the mammalian stress response. Grown nonhuman primates who were expos...
10.1038/nrn1683
These data indicate a potential neurobiological mechanism in non-human primates by which early-life stressors might contribute to adult psychopathology.
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/nrn1683
An epidemiological study that provides evidence of a gene-by-environment interaction, in which the response of an individual to environmental insults is moderated by genetic makeup.
10.1073/pnas.1208134110
62,403,624
Significance Under adverse environmental conditions, bacteria can form specialized antibiotic-resistant colonies called “biofilms.” In Staphylococcus epidermidis biofilms, a protein, Aap, links bacterial cells together but does so only in the presence of zinc ions. We have determined the atomic structure of an adhesive...
10.1038/nrmicro3161
This paper confirms the G5–E repeat structure from reference 34 and proposes a mechanism for Aap-promoted (and SasG-promoted) biofilm formation.
10.1073/pnas.1119456109
38,307,011
Staphylococcus aureus and Staphylococcus epidermidis form communities (called biofilms) on inserted medical devices, leading to infections that affect many millions of patients worldwide and cause substantial morbidity and mortality. As biofilms are resistant to antibiotics, device removal is often required to resolve ...
10.1038/nrmicro3161
This study provides the first description of the structure of the G5–E repeats of SasG that are involved in fibril formation.
10.1084/jem.20050125
104,089,427
The expression of Staphylococcus aureus adhesins in Lactococcus lactis identified clumping factor A (ClfA) and fibronectin-binding protein A (FnBPA) as critical for valve colonization in rats with experimental endocarditis. This study further analyzed their role in disease evolution. Infected animals were followed for ...
10.1038/nrmicro3161
This study uses expression of Fnb proteins and ClfA in Lactococcus lactis to show the role of their binding to fibrinogen and fibronectin in the pathogenesis of endocarditis.
10.1073/pnas.1109071108
40,339,751
Medical implants, like cardiovascular devices, improve the quality of life for countless individuals but may become infected with bacteria like Staphylococcus aureus . Such infections take the form of a biofilm, a structured community of bacterial cells adherent to the surface of a solid substrate. Every biofilm begins...
10.1038/nrmicro3161
This study shows that S. aureus bacteraemia isolates that infect cardiac devices have a higher affinity for fibronectin than those that only cause bacteraemia.
10.1073/pnas.0606863103
82,445,436
Staphylococcus aureus is the most common cause of hospital-acquired infection. Because of the emergence of antibiotic-resistant strains, these infections represent a serious public health threat. To develop a broadly protective vaccine, we tested cell wall-anchored surface proteins of S. aureus as antigens in a murine ...
10.1038/nrmicro3161
This report provides a systematic analysis of the protective efficacy of recombinant CWA proteins as antigens and shows that a combination of four antigens offers better protection than each antigen alone.
10.1084/jem.20092514
123,508,713
The current epidemic of hospital- and community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections has caused significant human morbidity, but a protective vaccine is not yet available. Prior infection with S. aureus is not associated with protective immunity. This phenomenon involves staphylococcal...
10.1038/nrmicro3161
This paper shows that recombinant protein A that lacks the ability to bind to IgG or IgM is a better immunogen than wild-type protein A.
10.1084/jem.20090097
40,522,564
Staphylococcus aureus infects hospitalized or healthy individuals and represents the most frequent cause of bacteremia, treatment of which is complicated by the emergence of methicillin-resistant S. aureus. We examined the ability of S. aureus to escape phagocytic clearance in blood and identified adenosine synthase A ...
10.1038/nrmicro3161
This paper provides a description of a novel function for the surface protein S. aureus adenosine synthase A (AdsA) in innate immune evasion.
10.1073/pnas.1400019111
59,275,516
Significance Most clinically used antibiotics are derived from bacterial small molecules produced by dedicated biosynthetic gene clusters. Recent investigations have indicated that the majority of these biosynthetic genes are inactive or “silent.” Identifying the triggers that lead to activation of silent clusters woul...
10.1038/nrmicro3496
This study describes a new high-throughput platform for discovering elicitors that activate silent BGCs.
10.1073/pnas.1206855109
107,308,319
In polymicrobial infections, microbes can interact with both the host immune system and one another through direct contact or the secretion of metabolites, affecting disease progression and treatment options. The thick mucus in the lungs of patients with cystic fibrosis is highly susceptible to polymicrobial infections...
10.1038/nrmicro3496
This study uses MALDI–IMS to directly visualize and identify metabolites produced by microorganisms growing on an agar plate, revealing a complex pattern of metabolite exchange between P. aeruginosa and A. fumigatus
10.1073/pnas.1019077108
83,417,374
There is a constant need for new and improved drugs to combat infectious diseases, cancer, and other major life-threatening conditions. The recent development of genomics-guided approaches for novel natural product discovery has stimulated renewed interest in the search for natural product-based drugs. Genome sequence ...
10.1038/nrmicro3496
This article reports that constitutive overexpression of a putative pathway-specific transcriptional activator induces BGC expression, leading to the discovery of the stambomycins, which are potential leads for the development of new anticancer agents.
10.1207/s15516709cog2703_8
85,569,716
Abstract This paper provides an overview of developments in a dual processing theory of automatic and controlled processing that began with the empirical and theoretical work described by Schneider and Shiffrin (1977) and Shiffrin and Schneider (1977) over a quarter century ago. A review of relevant empirical findings ...
10.1038/nrn2915
An excellent review of the differences between controlled and automatic processing in humans.
10.1073/pnas.0502762102
124,961,185
In this study, we used functional MRI (fMRI) at high field (3T) to track the time course of activation in the entire basal ganglia circuitry, as well as other motor-related structures, during the explicit learning of a sequence of finger movements over a month of training. Fourteen right-handed healthy volunteers had t...
10.1038/nrn2915
An early study in humans indicating that different striatal regions become engaged during different phases of motor learning.
10.1002/cne.902630102
67,621,210
Abstract With an antibody specific for L‐histidine decarboxylase (HD) in combination with immunohistochemical techniques and retrograde fluorescent tracing, the morphology, distribution, and projections of the histamineragic neurons of the posterior hypothalamus were studied in the adult male rat. Magnocellular neurons...
10.1038/nrn3526
This was the first study to identify functional heterogeneity among the histaminergic neurons projecting to different parts of the brain.
10.1038/sj.bjp.0704053
81,607,227
A study was made of the regulation of [ 3 H]‐γ‐aminobutyric acid ([ 3 H]‐GABA) release from slices of rat striatum by endogenous dopamine and exogenous histamine and a histamine H 3 ‐agonist. Depolarization‐induced release of [ 3 H]‐GABA was Ca 2+ ‐dependent and was increased in the presence of the dopamine D 2 recepto...
10.1038/nrn3526
One of the first studies to show that H 3 R interferes with dopaminergic regulation of GABA release from striatal neurons, a finding that is relevant for understanding PD, GTS and reward mechanisms.
10.1113/jphysiol.2010.203257
62,370,225
Non‐technical summary L‐Dopa is an effective medication for Parkinson's disease (PD), but loses efficiency with time. This can be delayed by treatment with histamine antagonists. We show histaminergic neurons in the hypothalamus controlling wakefulness are excited by L‐Dopa, which they can take up and transform to dopa...
10.1038/nrn3526
This study demonstrates the ability of the histaminergic neurons to take up and decarboxylate L-DOPA, a finding relevant for understanding the mechanisms of PD and L-DOPA-induced dyskinesia.
10.1126/science.1072810
82,122,716
Bphs controls Bordetella pertussis toxin (PTX)–induced vasoactive amine sensitization elicited by histamine (VAASH) and has an established role in autoimmunity. We report that congenic mapping links Bphs to the histamine H 1 receptor gene ( Hrh1 /H1R) and that H1R differs at three amino acid residues in VAASH-susceptib...
10.1038/nrn3526
The first of several papers from the same research group that identify the role of histamine receptors in EAE, a mouse model of MS.
10.1111/j.1476-5381.2009.00152.x
83,162,091
Background and purpose: Functional interactions between the G protein‐coupled dopamine D 1 and histamine H 3 receptors have been described in the brain. In the present study we investigated the existence of D 1 –H 3 receptor heteromers and their biochemical characteristics. Experimental approach: D 1 –H 3 receptor hete...
10.1038/nrn3526
This study identified that H 3 Rs and dopamine D1Rs can heteromerize, an essential finding for understanding striatal functions.
10.1152/physrev.2001.81.3.1143
41,064,337
Cerebellar Purkinje cells exhibit a unique type of synaptic plasticity, namely, long-term depression (LTD). When two inputs to a Purkinje cell, one from a climbing fiber and the other from a set of granule cell axons, are repeatedly associated, the input efficacy of the granule cell axons in exciting the Purkinje cell ...
10.1038/nrn962
A recent, thorough review of the 579 references about cerebellar LTD that had been published by the end of 2000.
10.1152/jn.1998.80.6.2963
32,906,217
Narasimhan, Kalyani, Isaac N. Pessah, and David J. Linden. Inositol-1,4,5-trisphosphate receptor-mediated Ca mobilization is not required for cerebellar long-term depression in reduced preparations. J. Neurophysiol. 80: 2963–2974, 1998. Cerebellar long-term depression (LTD) is a cellular model system of information sto...
10.1038/nrn962
This paper reports that Ins(1,4,5)P 3 -mediated Ca 2+ release from intracellular stores is not required for the induction of a reduced form of LTD, even though it is indispensable for LTD induction in cerebellar slices. This is one of the bases of the present assumption that mGluR1s and AMPARs are alternative mediators...
10.1073/pnas.92.18.8279
58,477,117
Of fundamental importance in understanding neuronal function is the unambiguous determination of the smallest unit of neuronal integration. It was recently suggested that a whole dendritic branchlet, including tens of spines, acts as the fundamental unit in terms of dendritic calcium dynamics in Purkinje cells. By cont...
10.1038/nrn962
Using two-photon excited fluorescence laser-scanning microscopy, individual spines of Purkinje cell dendrites were shown to be capable of independent Ca 2+ activation. Ca 2+ fluxes in spines showed a highly nonlinear dependence on membrane potential.
10.1042/bj20091960
81,760,114
FXTAS (fragile X-associated tremor/ataxia syndrome) is a late-onset neurodegenerative disorder that affects individuals who are carriers of premutation expansions (55–200 CGG repeats) in the 5′ untranslated region of the FMR1 (fragile X mental retardation 1) gene. The role of MD (mitochondrial dysfunction) in FXTAS was...
10.1038/nrneurol.2016.82
The first paper to document mitochondrial dysfunction in premutation carriers both with and without FXTAS.
10.1126/science.173.3997.652
83,548,119
Nerve cells in the monkey's prefrontal cortex and nucleus medialis dorsalis of the thalamus show changes of firing frequency associated with the performance of a delayed response test. Most cells increase firing during the cue presentation period or at the beginning of the ensuing delay; spike discharge higher than tha...
10.1038/nrn1033
A seminal paper demonstrating sustained activity in PFC neurons related to short-term memory of a stimulus over a delay period.
10.1162/08989290051137585
83,540,369
Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have been extensively used to explore the functional neuroanatomy of cognitive functions. Here we review 275 PET and fMRI studies of attention (sustained, selective, Stroop, orientation, divided), perception (object, face, space/motion,...
10.1038/nrn1033
A comprehensive review of the functional imaging literature regarding most aspects of cognition.
10.1177/026988119701100203
46,780,626
A series of discrete, parallel frontal-subcortical circuits have been demonstrated to link specific areas of the frontal lobe to areas within the basal ganglia and thalamus. A variety of circuit-specific behaviors can be described involving the dorsolateral prefrontal, orbitofrontal and anterior cingulate circuits. Int...
10.1038/nrn1033
This paper provides an excellent overview of the neural circuitry of the PFC and its relationship to behaviour.
10.1146/annurev.neuro.24.1.167
83,551,177
▪ Abstract The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of pat...
10.1038/nrn1033
A useful summary of research into PFC functions that also presents a detailed account of the guided activation model.
10.1146/annurev-ento-112408-085319
83,372,842
Despite the presence of many carbohydrolytic activities in insects, their cellulolytic mechanisms are poorly understood. Whereas cellulase genes are absent from the genomes of Drosophila melanogaster or Bombyx mori, other insects such as termites produce their own cellulases. Recent studies using molecular biological t...
10.1038/nrmicro3182
This review provides an excellent overview of the endogenous cellulolytic system of termites and was authored by the two scientists who contributed most essentially to its discovery.
10.1126/science.1165578
38,260,149
Termites harbor diverse symbiotic gut microorganisms, the majority of which are as yet uncultivable and their interrelationships unclear. Here, we present the complete genome sequence of the uncultured Bacteroidales endosymbiont of the cellulolytic protist Pseudotrichonympha grassii, which accounts for 70% of the bacte...
10.1038/nrmicro3182
This paper reports the second genome of a flagellate symbiont, documenting a crucial role in nitrogen fixation and the capacity for ammonia assimilation and amino acid upgrading.
10.1038/ismej.2007.62
104,434,165
Abstract The key role of free hydrogen in the digestion of lignocellulose by wood-feeding lower termites and their symbiotic gut microbiota has been conceptually outlined in the past decades but remains to be quantitatively analyzed in situ. Using Reticulitermes santonensis, Zootermopsis nevadensis and Cryptotermes sec...
10.1038/nrmicro3182
This paper reports the in situ assessment of hydrogen turnover and other metabolic fluxes in the hindgut of several lower termites, combining microsensor and isotope dilution techniques.
10.1126/science.283.5402.686
42,494,189
Pure cultures of termite gut spirochetes were obtained and were shown to catalyze the synthesis of acetate from H 2 plus CO 2 . The 16 S ribosomal DNA sequences of two strains were 98 percent similar and were affiliated with those of the genus Treponema . However, neither was closely related to any known treponeme. The...
10.1038/nrmicro3182
This study reports the isolation of termite gut spirochaetes in pure culture and the basis for their identification as the major hydrogen sink in wood-feeding termites; it was a milestone in termite gut research.
10.1111/j.1462-2920.2011.02648.x
4,583,774
Summary Soil‐feeding termites play important roles in the dynamics of carbon and nitrogen in tropical soils. Through the mineralization of nitrogenous humus components, their intestinal tracts accumulate enormous amounts of ammonia, and nitrate and nitrite concentrations are several orders of magnitude above those in t...
10.1038/nrmicro3182
This paper analyses nitrogen metabolism in soil-feeding termites using isotope tracers and provides evidence for the production of N 2 O and an unusual ammonia-oxidizing activity in the posterior hindgut.
10.1073/pnas.0801389105
104,092,696
Termites harbor a symbiotic gut microbial community that is responsible for their ability to thrive on recalcitrant plant matter. The community comprises diverse microorganisms, most of which are as yet uncultivable; the detailed symbiotic mechanism remains unclear. Here, we present the first complete genome sequence o...
10.1038/nrmicro3182
This paper reports the first genome analysis of a flagellate endosymbiont that maintained its biosynthetic pathways for vitamins and amino acids despite considerable genome erosion.
10.1073/pnas.0800946105
100,983,130
How the billions of synapses in the adult mammalian brain are precisely specified remains one of the fundamental questions of neuroscience. Although a genetic program is likely to encode the basic neural blueprint, much evidence suggests that experience-driven activity through NMDA receptors wires up neuronal circuits ...
10.1038/nrn3642
The authors of this study present the surprising finding that chronic inhibition of NMDARs results in fewer AMPA-silent synapses.
10.1002/dvg.20440
124,518,226
Abstract The NG2 glycoprotein is a type I membrane protein expressed by immature cells in the developing and adult mouse. NG2+ cells of the embryonic and adult brain have been principally viewed as oligodendrocyte precursor cells but have additionally been considered a fourth glial class. They are likely to be a hetero...
10.1038/nrn2495
This paper describes the distribution of the reporter EYFP in the new transgenic mouse line in which EYFP was inserted into the Cspg4 locus.
10.1242/dev.004895
82,876,041
NG2 glia constitute a fourth major glial cell type in the mammalian central nervous system (CNS) that is distinct from other cell types. Although circumstantial evidence suggests that some NG2 glia differentiate into oligodendrocytes, their in vivo fate has not been directly examined. We have used the bacterial artific...
10.1038/nrn2495
Fate mapping of polydendrocytes using NG2–Cre-transgenic mice showed that the predominant fate of these cells is to differentiate into oligodendrocytes and a subset of protoplasmic astrocytes in the grey matter.
10.1242/dev.02847
82,903,282
The mechanisms underlying astrocyte heterogeneity in the developing mouse brain are poorly understood. The bHLH transcription factor Olig2 is essential for motoneuron and oligodendrocyte formation; however, its role in astrocyte development remains obscure. During cortical development, Olig2 is transiently expressed in...
10.1038/nrn2495
Using different Cre driver lines crossed to floxed Olig2 mice, Olig2 was deleted in different populations. Differential astrogliogenic effects of Olig2 deletion are seen in GFAP+ early stem cells and in Cnp + oligodendrocyte lineage cells.
10.1101/gad.309404
38,537,484
We showed previously that purified rat oligodendrocyte precursor cells (OPCs) can be induced by extracellular signals to convert to multipotent neural stem-like cells (NSLCs), which can then generate both neurons and glial cells. Because the conversion of precursor cells to stem-like cells is of both intellectual and p...
10.1038/nrn2495
This paper extended the authors' earlier finding that isolated OPCs can be reprogrammed to turn into multipotent cells and described a role for chromatin remodelling in this conversion.