5,728 results match your criteria Nature Neuroscience [Journal]


Cell-of-origin susceptibility to glioblastoma formation declines with neural lineage restriction.

Nat Neurosci 2019 Feb 18. Epub 2019 Feb 18.

Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

The contribution of lineage identity and differentiation state to malignant transformation is controversial. We have previously shown that adult neural stem and early progenitor cells give origin to glioblastoma. Here we systematically assessed the tumor-initiating potential of adult neural populations at various stages of lineage progression. Read More

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http://dx.doi.org/10.1038/s41593-018-0333-8DOI Listing
February 2019

The DNA modification N6-methyl-2'-deoxyadenosine (m6dA) drives activity-induced gene expression and is required for fear extinction.

Nat Neurosci 2019 Feb 18. Epub 2019 Feb 18.

Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.

DNA modification is known to regulate experience-dependent gene expression. However, beyond cytosine methylation and its oxidated derivatives, very little is known about the functional importance of chemical modifications on other nucleobases in the brain. Here we report that in adult mice trained in fear extinction, the DNA modification N6-methyl-2'-deoxyadenosine (m6dA) accumulates along promoters and coding sequences in activated prefrontal cortical neurons. Read More

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http://dx.doi.org/10.1038/s41593-019-0339-xDOI Listing
February 2019

Author Correction: Neural computations of threat in the aftermath of combat trauma.

Nat Neurosci 2019 Feb 13. Epub 2019 Feb 13.

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

The original and corrected figures are shown in the accompanying Author Correction. Read More

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http://www.nature.com/articles/s41593-019-0356-9
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http://dx.doi.org/10.1038/s41593-019-0356-9DOI Listing
February 2019
2 Reads

Whither variability?

Nat Neurosci 2019 Feb 11. Epub 2019 Feb 11.

Dept. of Physiology and Biophysics and UW Institute for Neuroengineering, University of Washington, Seattle, Washington, USA.

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http://dx.doi.org/10.1038/s41593-019-0344-0DOI Listing
February 2019

Reduced mitochondrial fusion and Huntingtin levels contribute to impaired dendritic maturation and behavioral deficits in Fmr1-mutant mice.

Nat Neurosci 2019 Feb 11. Epub 2019 Feb 11.

Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.

Fragile X syndrome results from a loss of the RNA-binding protein fragile X mental retardation protein (FMRP). How FMRP regulates neuronal development and function remains unclear. Here we show that FMRP-deficient immature neurons exhibit impaired dendritic maturation, altered expression of mitochondrial genes, fragmented mitochondria, impaired mitochondrial function, and increased oxidative stress. Read More

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http://dx.doi.org/10.1038/s41593-019-0338-yDOI Listing
February 2019

Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer's disease mouse models.

Nat Neurosci 2019 Feb 11. Epub 2019 Feb 11.

Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.

Cerebral blood flow (CBF) reductions in Alzheimer's disease patients and related mouse models have been recognized for decades, but the underlying mechanisms and resulting consequences for Alzheimer's disease pathogenesis remain poorly understood. In APP/PS1 and 5xFAD mice we found that an increased number of cortical capillaries had stalled blood flow as compared to in wild-type animals, largely due to neutrophils that had adhered in capillary segments and blocked blood flow. Administration of antibodies against the neutrophil marker Ly6G reduced the number of stalled capillaries, leading to both an immediate increase in CBF and rapidly improved performance in spatial and working memory tasks. Read More

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http://dx.doi.org/10.1038/s41593-018-0329-4DOI Listing
February 2019
1 Read

Spinal stretch reflexes support efficient hand control.

Nat Neurosci 2019 Feb 11. Epub 2019 Feb 11.

Brain and Mind Institute, Western University, London, Ontario, Canada.

Motor behaviour is most efficiently controlled by correcting only disturbances that influence task success. It is currently thought that such control is computed within a transcortical feedback pathway. Here we show that, for postural hand control, even the fastest spinal feedback pathway can produce efficient corrective responses, forcing a re-evaluation of how the nervous system derives the control laws that support motor behavior. Read More

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http://dx.doi.org/10.1038/s41593-019-0336-0DOI Listing
February 2019

Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease.

Nat Neurosci 2019 Feb 11. Epub 2019 Feb 11.

Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Accumulation of damaged mitochondria is a hallmark of aging and age-related neurodegeneration, including Alzheimer's disease (AD). The molecular mechanisms of impaired mitochondrial homeostasis in AD are being investigated. Here we provide evidence that mitophagy is impaired in the hippocampus of AD patients, in induced pluripotent stem cell-derived human AD neurons, and in animal AD models. Read More

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http://dx.doi.org/10.1038/s41593-018-0332-9DOI Listing
February 2019

Publisher Correction: A diverse range of factors affect the nature of neural representations underlying short-term memory.

Nat Neurosci 2019 Feb 6. Epub 2019 Feb 6.

Center for Neural Science, New York University, New York, NY, USA.

The original and corrected figures are shown in the accompanying Publisher Correction. Read More

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http://dx.doi.org/10.1038/s41593-019-0348-9DOI Listing
February 2019

Concurrent visual and motor selection during visual working memory guided action.

Nat Neurosci 2019 Feb 4. Epub 2019 Feb 4.

Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, Department of Psychiatry, University of Oxford, Oxford, UK.

Visual working memory enables us to hold onto past sensations in anticipation that these may become relevant for guiding future actions. Yet laboratory tasks have treated visual working memories in isolation from their prospective actions and have focused on the mechanisms of memory retention rather than utilization. To understand how visual memories become used for action, we linked individual memory items to particular actions and independently tracked the neural dynamics of visual and motor selection when memories became used for action. Read More

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http://dx.doi.org/10.1038/s41593-018-0335-6DOI Listing
February 2019

Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning.

Nat Neurosci 2019 Feb 4. Epub 2019 Feb 4.

Center for Quantitative Health, Center for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.

Synapse density is reduced in postmortem cortical tissue from schizophrenia patients, which is suggestive of increased synapse elimination. Using a reprogrammed in vitro model of microglia-mediated synapse engulfment, we demonstrate increased synapse elimination in patient-derived neural cultures and isolated synaptosomes. This excessive synaptic pruning reflects abnormalities in both microglia-like cells and synaptic structures. Read More

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http://dx.doi.org/10.1038/s41593-018-0334-7DOI Listing
February 2019
16.095 Impact Factor

Dorsolateral septum somatostatin interneurons gate mobility to calibrate context-specific behavioral fear responses.

Nat Neurosci 2019 Feb 4. Epub 2019 Feb 4.

Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.

Adaptive fear responses to external threats rely upon efficient relay of computations underlying contextual encoding to subcortical circuits. Brain-wide analysis of highly coactivated ensembles following contextual fear discrimination identified the dorsolateral septum (DLS) as a relay of the dentate gyrus-CA3 circuit. Retrograde monosynaptic tracing and electrophysiological whole-cell recordings demonstrated that DLS somatostatin-expressing interneurons (SST-INs) receive direct CA3 inputs. Read More

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http://dx.doi.org/10.1038/s41593-018-0330-yDOI Listing
February 2019

Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.

Nat Neurosci 2019 Feb 4. Epub 2019 Feb 4.

Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.

Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analyzed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. Read More

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http://dx.doi.org/10.1038/s41593-018-0326-7DOI Listing
February 2019
1 Read
16.095 Impact Factor

Differentiation of human pluripotent stem cells into neurons or cortical organoids requires transcriptional co-regulation by UTX and 53BP1.

Nat Neurosci 2019 Feb 4. Epub 2019 Feb 4.

Department of Developmental Neurobiology and Division of Developmental Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.

UTX is a chromatin modifier required for development and neural lineage specification, but how it controls these biological processes is unclear. To determine the molecular mechanisms of UTX, we identified novel UTX protein interaction partners. Here we show that UTX and 53BP1 directly interact and co-occupy promoters in human embryonic stem cells and differentiating neural progenitor cells. Read More

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http://dx.doi.org/10.1038/s41593-018-0328-5DOI Listing
February 2019
1 Read

Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures.

Nat Neurosci 2019 Jan 28. Epub 2019 Jan 28.

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.

Investigating human oligodendrogenesis and the interaction of oligodendrocytes with neurons and astrocytes would accelerate our understanding of the mechanisms underlying white matter disorders. However, this is challenging because of the limited accessibility of functional human brain tissue. Here, we developed a new differentiation method of human induced pluripotent stem cells to generate three-dimensional brain organoids that contain oligodendrocytes as well as neurons and astrocytes, called human oligodendrocyte spheroids. Read More

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http://dx.doi.org/10.1038/s41593-018-0316-9DOI Listing
January 2019
1 Read

State-dependent encoding of sound and behavioral meaning in a tertiary region of the ferret auditory cortex.

Nat Neurosci 2019 Jan 28. Epub 2019 Jan 28.

Institute for Systems Research, Department of Electrical and Computer Engineering, University of Maryland, College Park, MD, USA.

In higher sensory cortices, there is a gradual transformation from sensation to perception and action. In the auditory system, this transformation is revealed by responses in the rostral ventral posterior auditory field (VPr), a tertiary area in the ferret auditory cortex, which shows long-term learning in trained compared to naïve animals, arising from selectively enhanced responses to behaviorally relevant target stimuli. This enhanced representation is further amplified during active performance of spectral or temporal auditory discrimination tasks. Read More

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http://www.nature.com/articles/s41593-018-0317-8
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http://dx.doi.org/10.1038/s41593-018-0317-8DOI Listing
January 2019
2 Reads

A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment.

Nat Neurosci 2019 Jan 28. Epub 2019 Jan 28.

Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.

There is mounting evidence that seemingly diverse psychiatric disorders share genetic etiology, but the biological substrates mediating this overlap are not well characterized. Here we leverage the unique Integrative Psychiatric Research Consortium (iPSYCH) study, a nationally representative cohort ascertained through clinical psychiatric diagnoses indicated in Danish national health registers. We confirm previous reports of individual and cross-disorder single-nucleotide polymorphism heritability for major psychiatric disorders and perform a cross-disorder genome-wide association study. Read More

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http://dx.doi.org/10.1038/s41593-018-0320-0DOI Listing
January 2019

Intersectional monosynaptic tracing for dissecting subtype-specific organization of GABAergic interneuron inputs.

Nat Neurosci 2019 Jan 28. Epub 2019 Jan 28.

Development and Function of Inhibitory Neural Circuits, Max Planck Florida Institute for Neuroscience, Jupiter, FL, USA.

Functionally and anatomically distinct cortical substructures, such as areas or layers, contain different principal neuron (PN) subtypes that generate output signals representing particular information. Various types of cortical inhibitory interneurons (INs) differentially but coordinately regulate PN activity. Despite a potential determinant for functional specialization of PN subtypes, the spatial organization of IN subtypes that innervate defined PN subtypes remains unknown. Read More

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http://dx.doi.org/10.1038/s41593-018-0322-yDOI Listing
January 2019

Temporal evolution of cortical ensembles promoting remote memory retrieval.

Nat Neurosci 2019 Jan 28. Epub 2019 Jan 28.

Department of Biology, Stanford University, Stanford, CA, USA.

Memories of fearful events can last a lifetime. The prelimbic (PL) cortex, a subregion of prefrontal cortex, plays a critical role in fear memory retrieval over time. Most studies have focused on acquisition, consolidation, and retrieval of recent memories, but much less is known about the neural mechanisms of remote memory. Read More

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http://www.nature.com/articles/s41593-018-0318-7
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http://dx.doi.org/10.1038/s41593-018-0318-7DOI Listing
January 2019
3 Reads

Astrocyte function from information processing to cognition and cognitive impairment.

Nat Neurosci 2019 Feb 21;22(2):154-166. Epub 2019 Jan 21.

Department of Fundamental Neuroscience, University of Lausanne, Lausanne, Switzerland.

Astrocytes serve important roles that affect recruitment and function of neurons at the local and network levels. Here we review the contributions of astrocyte signaling to synaptic plasticity, neuronal network oscillations, and memory function. The roles played by astrocytes are not fully understood, but astrocytes seem to contribute to memory consolidation and seem to mediate the effects of vigilance and arousal on memory performance. Read More

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http://dx.doi.org/10.1038/s41593-018-0325-8DOI Listing
February 2019
2 Reads
16.095 Impact Factor

Acute silencing of hippocampal CA3 reveals a dominant role in place field responses.

Nat Neurosci 2019 Jan 21. Epub 2019 Jan 21.

Department of Psychology, University of California, Berkeley, Berkeley, CA, USA.

Neurons in hippocampal output area CA1 are thought to exhibit redundancy across cortical and hippocampal inputs. Here we show instead that acute silencing of CA3 terminals drastically reduces place field responses for many CA1 neurons, while a smaller number are unaffected or have increased responses. These results imply that CA3 is the predominant driver of CA1 place cells under normal conditions, while also revealing heterogeneity in input dominance across cells. Read More

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http://dx.doi.org/10.1038/s41593-018-0321-zDOI Listing
January 2019

Human cognition involves the dynamic integration of neural activity and neuromodulatory systems.

Nat Neurosci 2019 Feb 21;22(2):289-296. Epub 2019 Jan 21.

Department of Psychology, Stanford University, Stanford, CA, USA.

The human brain integrates diverse cognitive processes into a coherent whole, shifting fluidly as a function of changing environmental demands. Despite recent progress, the neurobiological mechanisms responsible for this dynamic system-level integration remain poorly understood. Here we investigated the spatial, dynamic, and molecular signatures of system-wide neural activity across a range of cognitive tasks. Read More

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http://dx.doi.org/10.1038/s41593-018-0312-0DOI Listing
February 2019
1 Read

Neural computations of threat in the aftermath of combat trauma.

Nat Neurosci 2019 Jan 21. Epub 2019 Jan 21.

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

By combining computational, morphological, and functional analyses, this study relates latent markers of associative threat learning to overt post-traumatic stress disorder (PTSD) symptoms in combat veterans. Using reversal learning, we found that symptomatic veterans showed greater physiological adjustment to cues that did not predict what they had expected, indicating greater sensitivity to prediction errors for negative outcomes. This exaggerated weighting of prediction errors shapes the dynamic learning rate (associability) and value of threat predictive cues. Read More

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http://dx.doi.org/10.1038/s41593-018-0315-xDOI Listing
January 2019
2 Reads

Microvascular endothelial cells engulf myelin debris and promote macrophage recruitment and fibrosis after neural injury.

Nat Neurosci 2019 Jan 21. Epub 2019 Jan 21.

Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, USA.

The clearance of damaged myelin sheaths is critical to ensure functional recovery from neural injury. Here we show a previously unidentified role for microvessels and their lining endothelial cells in engulfing myelin debris in spinal cord injury (SCI) and experimental autoimmune encephalomyelitis (EAE). We demonstrate that IgG opsonization of myelin debris is required for its effective engulfment by endothelial cells and that the autophagy-lysosome pathway is crucial for degradation of engulfed myelin debris. Read More

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http://www.nature.com/articles/s41593-018-0324-9
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http://dx.doi.org/10.1038/s41593-018-0324-9DOI Listing
January 2019
7 Reads
16.095 Impact Factor

Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.

Nat Neurosci 2019 Feb 21;22(2):229-242. Epub 2019 Jan 21.

Department of Psychiatry, McLean Hospital/Harvard Medical School, Belmont, MA, USA.

We generated cortical interneurons (cINs) from induced pluripotent stem cells derived from 14 healthy controls and 14 subjects with schizophrenia. Both healthy control cINs and schizophrenia cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo. However, schizophrenia cINs had dysregulated expression of protocadherin genes, which lie within documented schizophrenia loci. Read More

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http://dx.doi.org/10.1038/s41593-018-0313-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373728PMC
February 2019
3 Reads

A diverse range of factors affect the nature of neural representations underlying short-term memory.

Nat Neurosci 2019 Feb 24;22(2):275-283. Epub 2019 Jan 24.

Center for Neural Science, New York University, New York, NY, USA.

Sequential and persistent activity models are two prominent models of short-term memory in neural circuits. In persistent activity models, memories are represented in persistent or nearly persistent activity patterns across a population of neurons, whereas in sequential models, memories are represented dynamically by a sequential activity pattern across the population. Experimental evidence for both models has been reported previously. Read More

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http://dx.doi.org/10.1038/s41593-018-0314-yDOI Listing
February 2019
1 Read

Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus-CA3 projection.

Nat Neurosci 2019 Feb 21;22(2):205-217. Epub 2019 Jan 21.

Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX, USA.

Nuclear receptor corepressor 1 (NCOR1) and NCOR2 (also known as SMRT) regulate gene expression by activating histone deacetylase 3 through their deacetylase activation domain (DAD). We show that mice with DAD knock-in mutations have memory deficits, reduced anxiety levels, and reduced social interactions. Mice with NCOR1 and NORC2 depletion specifically in GABAergic neurons (NS-V mice) recapitulated the memory deficits and had reduced GABA receptor subunit α2 (GABRA2) expression in lateral hypothalamus GABAergic (LH) neurons. Read More

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http://www.nature.com/articles/s41593-018-0311-1
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http://dx.doi.org/10.1038/s41593-018-0311-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361549PMC
February 2019
5 Reads

Publisher Correction: Midbrain activity can explain perceptual decisions during an attention task.

Nat Neurosci 2019 Jan 15. Epub 2019 Jan 15.

Laboratory of Sensorimotor Research, National Eye Institute, NIH, Bethesda, MD, USA.

The original and corrected figures are shown in the accompanying Publisher Correction. Read More

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http://dx.doi.org/10.1038/s41593-018-0319-6DOI Listing
January 2019
1 Read

Author Correction: PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1.

Nat Neurosci 2019 Jan 14. Epub 2019 Jan 14.

Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA.

In the version of this article initially published, what was originally described as 'conditioned place preference' in a two-chamber mouse experiment could be better described as 'conditioned place avoidance'. Read More

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http://www.nature.com/articles/s41593-018-0323-x
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http://dx.doi.org/10.1038/s41593-018-0323-xDOI Listing
January 2019
5 Reads
16.095 Impact Factor

Perceptual bias reveals slow-updating in autism and fast-forgetting in dyslexia.

Nat Neurosci 2019 Feb 14;22(2):256-264. Epub 2019 Jan 14.

Edmond and Lily Safra Center for Brain Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.

Individuals with autism and individuals with dyslexia both show reduced use of previous sensory information (stimuli statistics) in perceptual tasks, even though these are very different neurodevelopmental disorders. To better understand how past sensory information influences the perceptual experience in these disorders, we first investigated the trial-by-trial performance of neurotypical participants in a serial discrimination task. Neurotypical participants overweighted recent stimuli, revealing fast updating of internal sensory models, which is adaptive in changing environments. Read More

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http://dx.doi.org/10.1038/s41593-018-0308-9DOI Listing
February 2019
3 Reads

Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration.

Nat Neurosci 2019 Feb 14;22(2):180-190. Epub 2019 Jan 14.

Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, USA.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are associated with loss of nuclear transactive response DNA-binding protein 43 (TDP-43). Here we identify that TDP-43 regulates expression of the neuronal growth-associated factor stathmin-2. Lowered TDP-43 levels, which reduce its binding to sites within the first intron of stathmin-2 pre-messenger RNA, uncover a cryptic polyadenylation site whose utilization produces a truncated, non-functional mRNA. Read More

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http://www.nature.com/articles/s41593-018-0293-z
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http://dx.doi.org/10.1038/s41593-018-0293-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348009PMC
February 2019
5 Reads

Cortical microcircuitry of performance monitoring.

Nat Neurosci 2019 Feb 14;22(2):265-274. Epub 2019 Jan 14.

Department of Psychology, Vanderbilt Vision Research Center, Center for Integrative & Cognitive Neuroscience, Vanderbilt University, Nashville, TN, USA.

The medial frontal cortex enables performance monitoring, indexed by the error-related negativity (ERN) and manifested by performance adaptations. We recorded electroencephalogram over and neural spiking across all layers of the supplementary eye field, an agranular cortical area, in monkeys performing a saccade-countermanding (stop signal) task. Neurons signaling error production, feedback predicting reward gain or loss, and delivery of fluid reward had different spike widths and were concentrated differently across layers. Read More

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http://dx.doi.org/10.1038/s41593-018-0309-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348027PMC
February 2019

Neuronal brain-region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability.

Nat Neurosci 2019 Feb 14;22(2):307-316. Epub 2019 Jan 14.

Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Epigenetic modifications confer stable transcriptional patterns in the brain, and both normal and abnormal brain function involve specialized brain regions. We examined DNA methylation by whole-genome bisulfite sequencing in neuronal and non-neuronal populations from four brain regions (anterior cingulate gyrus, hippocampus, prefrontal cortex, and nucleus accumbens) as well as chromatin accessibility in the latter two. We find pronounced differences in both CpG and non-CpG methylation (CG-DMRs and CH-DMRs) only in neuronal cells across brain regions. Read More

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http://www.nature.com/articles/s41593-018-0297-8
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http://dx.doi.org/10.1038/s41593-018-0297-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348048PMC
February 2019
5 Reads

Active control of arousal by a locus coeruleus GABAergic circuit.

Nat Neurosci 2019 Feb 14;22(2):218-228. Epub 2019 Jan 14.

Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.

Arousal responses linked to locus coeruleus noradrenergic (LC-NA) activity affect cognition. However, the mechanisms that control modes of LC-NA activity remain unknown. Here, we reveal a local population of GABAergic neurons (LC-GABA) capable of modulating LC-NA activity and arousal. Read More

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http://dx.doi.org/10.1038/s41593-018-0305-zDOI Listing
February 2019

Task representations in neural networks trained to perform many cognitive tasks.

Nat Neurosci 2019 Feb 14;22(2):297-306. Epub 2019 Jan 14.

Center for Neural Science, New York University, New York, NY, USA.

The brain has the ability to flexibly perform many tasks, but the underlying mechanism cannot be elucidated in traditional experimental and modeling studies designed for one task at a time. Here, we trained single network models to perform 20 cognitive tasks that depend on working memory, decision making, categorization, and inhibitory control. We found that after training, recurrent units can develop into clusters that are functionally specialized for different cognitive processes, and we introduce a simple yet effective measure to quantify relationships between single-unit neural representations of tasks. Read More

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http://dx.doi.org/10.1038/s41593-018-0310-2DOI Listing
February 2019

Time is just a memory.

Nat Neurosci 2019 Feb;22(2):151-153

Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

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http://dx.doi.org/10.1038/s41593-018-0331-xDOI Listing
February 2019

ALS-implicated protein TDP-43 sustains levels of STMN2, a mediator of motor neuron growth and repair.

Nat Neurosci 2019 Feb 14;22(2):167-179. Epub 2019 Jan 14.

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.

The findings that amyotrophic lateral sclerosis (ALS) patients almost universally display pathological mislocalization of the RNA-binding protein TDP-43 and that mutations in its gene cause familial ALS have nominated altered RNA metabolism as a disease mechanism. However, the RNAs regulated by TDP-43 in motor neurons and their connection to neuropathy remain to be identified. Here we report transcripts whose abundances in human motor neurons are sensitive to TDP-43 depletion. Read More

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http://www.nature.com/articles/s41593-018-0300-4
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http://dx.doi.org/10.1038/s41593-018-0300-4DOI Listing
February 2019
23 Reads

Precise temporal memories are supported by the lateral entorhinal cortex in humans.

Nat Neurosci 2019 Feb 14;22(2):284-288. Epub 2019 Jan 14.

Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA, USA.

There is accumulating evidence that the entorhinal-hippocampal network is important for temporal memory. However, relatively little is known about the precise neurobiological mechanisms underlying memory for time. In particular, whether the lateral entorhinal cortex (LEC) is involved in temporal processing remains an open question. Read More

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http://dx.doi.org/10.1038/s41593-018-0303-1DOI Listing
February 2019

Publisher Correction: Genome-wide association study of delay discounting in 23,217 adult research participants of European ancestry.

Nat Neurosci 2019 Jan 8. Epub 2019 Jan 8.

Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.

The author list was in the wrong order in the HTML version of the original article and in the HTML version of the original correction notice. This has been corrected to show the 23andMe Research Team as the fourth author and Abraham A. Palmer as the last author in both places. Read More

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http://www.nature.com/articles/s41593-018-0306-y
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http://dx.doi.org/10.1038/s41593-018-0306-yDOI Listing
January 2019
8 Reads

Back to baseline: sleep recalibrates synapses.

Nat Neurosci 2019 Feb;22(2):149-151

Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany.

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http://dx.doi.org/10.1038/s41593-018-0327-6DOI Listing
February 2019

Pathological priming causes developmental gene network heterochronicity in autistic subject-derived neurons.

Nat Neurosci 2019 Feb 7;22(2):243-255. Epub 2019 Jan 7.

Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.

Autism spectrum disorder (ASD) is thought to emerge during early cortical development. However, the exact developmental stages and associated molecular networks that prime disease propensity are elusive. To profile early neurodevelopmental alterations in ASD with macrocephaly, we monitored subject-derived induced pluripotent stem cells (iPSCs) throughout the recapitulation of cortical development. Read More

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http://dx.doi.org/10.1038/s41593-018-0295-xDOI Listing
February 2019
3 Reads
16.095 Impact Factor

Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE.

Nat Neurosci 2019 Feb 7;22(2):191-204. Epub 2019 Jan 7.

Chair of Metabolic Biochemistry, Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.

Coding variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are associated with late-onset Alzheimer's disease (AD). We demonstrate that amyloid plaque seeding is increased in the absence of functional Trem2. Increased seeding is accompanied by decreased microglial clustering around newly seeded plaques and reduced plaque-associated apolipoprotein E (ApoE). Read More

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http://www.nature.com/articles/s41593-018-0296-9
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http://dx.doi.org/10.1038/s41593-018-0296-9DOI Listing
February 2019
9 Reads
16.095 Impact Factor

Panoptic imaging of transparent mice reveals whole-body neuronal projections and skull-meninges connections.

Nat Neurosci 2019 Feb 31;22(2):317-327. Epub 2018 Dec 31.

Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, Munich, Germany.

Analysis of entire transparent rodent bodies after clearing could provide holistic biological information in health and disease, but reliable imaging and quantification of fluorescent protein signals deep inside the tissues has remained a challenge. Here, we developed vDISCO, a pressure-driven, nanobody-based whole-body immunolabeling technology to enhance the signal of fluorescent proteins by up to two orders of magnitude. This allowed us to image and quantify subcellular details through bones, skin and highly autofluorescent tissues of intact transparent mice. Read More

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http://dx.doi.org/10.1038/s41593-018-0301-3DOI Listing
February 2019
1 Read

Publisher Correction: Motor primitives in space and time via targeted gain modulation in cortical networks.

Nat Neurosci 2018 Dec 19. Epub 2018 Dec 19.

Centre for Neural Circuits and Behaviour, University of Oxford, Oxford, UK.

In the version of this article initially published, in the PDF, equations (2) and (4) erroneously displayed a curly bracket on the right hand side of the equation. This should not be there. The errors have been corrected in the PDF version of the article. Read More

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http://www.nature.com/articles/s41593-018-0307-x
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http://dx.doi.org/10.1038/s41593-018-0307-xDOI Listing
December 2018
1 Read

TDP-43 shapeshifts to encipher FTD severity.

Nat Neurosci 2019 Jan;22(1):3-5

Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

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http://www.nature.com/articles/s41593-018-0299-6
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http://dx.doi.org/10.1038/s41593-018-0299-6DOI Listing
January 2019
8 Reads

TDP-43 extracted from frontotemporal lobar degeneration subject brains displays distinct aggregate assemblies and neurotoxic effects reflecting disease progression rates.

Nat Neurosci 2019 Jan 17;22(1):65-77. Epub 2018 Dec 17.

Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

Accumulation of abnormally phosphorylated TDP-43 (pTDP-43) is the main pathology in affected neurons of people with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Morphological diversity and neuroanatomical distribution of pTDP-43 accumulations allowed classification of FTLD cases into at least four subtypes, which are correlated with clinical presentations and genetic causes. To understand the molecular basis of this heterogeneity, we developed SarkoSpin, a new method for biochemical isolation of pathological TDP-43. Read More

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http://dx.doi.org/10.1038/s41593-018-0294-yDOI Listing
January 2019

Invasion of white matter tracts by glioma stem cells is regulated by a NOTCH1-SOX2 positive-feedback loop.

Nat Neurosci 2019 Jan 17;22(1):91-105. Epub 2018 Dec 17.

Institute of Pathology and Southwest Cancer Center, Key Laboratory of the Ministry of Education, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Early invasive growth along specific anatomical structures, especially the white matter tract, is regarded as one of the main causes of poor therapeutic outcome of people with gliomas. We show that some glioma stem cells (GSCs) are preferentially located along white matter tracts, which exhibit a demyelinated phenotype, at the invasive frontier of glioma tissues. These GSCs are CD133Notch1, whereas the nerve fibers express the Notch ligand Jagged1. Read More

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http://dx.doi.org/10.1038/s41593-018-0285-zDOI Listing
January 2019
1 Read
16.095 Impact Factor

Epigenome-wide study uncovers large-scale changes in histone acetylation driven by tau pathology in aging and Alzheimer's human brains.

Nat Neurosci 2019 Jan 17;22(1):37-46. Epub 2018 Dec 17.

Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, USA.

Accumulation of tau and amyloid-β are two pathologic hallmarks of Alzheimer's disease. We conducted an epigenome-wide association study using the histone 3 lysine 9 acetylation (H3K9ac) mark in 669 aged human prefrontal cortices; in contrast with amyloid-β, tau protein burden had a broad effect on the epigenome, affecting 5,990 of 26,384 H3K9ac domains. Tau-related alterations aggregated in large genomic segments reflecting spatial chromatin organization, and the magnitude of these effects correlated with the segment's nuclear lamina association. Read More

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http://dx.doi.org/10.1038/s41593-018-0291-1DOI Listing
January 2019

Efficient coding of subjective value.

Nat Neurosci 2019 Jan 17;22(1):134-142. Epub 2018 Dec 17.

Zurich Center for Neuroeconomics (ZNE), Department of Economics, University of Zurich, Zurich, Switzerland.

Preference-based decisions are essential for survival, for instance, when deciding what we should (not) eat. Despite their importance, preference-based decisions are surprisingly variable and can appear irrational in ways that have defied mechanistic explanations. Here we propose that subjective valuation results from an inference process that accounts for the structure of values in the environment and that maximizes information in value representations in line with demands imposed by limited coding resources. Read More

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http://dx.doi.org/10.1038/s41593-018-0292-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314450PMC
January 2019

Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry.

Nat Neurosci 2019 Jan 17;22(1):78-90. Epub 2018 Dec 17.

Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Microglia, the specialized innate immune cells of the CNS, play crucial roles in neural development and function. Different phenotypes and functions have been ascribed to rodent microglia, but little is known about human microglia (huMG) heterogeneity. Difficulties in procuring huMG and their susceptibility to cryopreservation damage have limited large-scale studies. Read More

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http://www.nature.com/articles/s41593-018-0290-2
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http://dx.doi.org/10.1038/s41593-018-0290-2DOI Listing
January 2019
15 Reads