Abstract：
:By analyzing the whole-exome sequences of 4,264 schizophrenia cases, 9,343 controls and 1,077 trios, we identified a genome-wide significant association between rare loss-of-function (LoF) variants in SETD1A and risk for schizophrenia (P = 3.3 × 10(-9)). We found only two heterozygous LoF variants in 45,376 exomes from individuals without a neuropsychiatric diagnosis, indicating that SETD1A is substantially depleted of LoF variants in the general population. Seven of the ten individuals with schizophrenia carrying SETD1A LoF variants also had learning difficulties. We further identified four SETD1A LoF carriers among 4,281 children with severe developmental disorders and two more carriers in an independent sample of 5,720 Finnish exomes, both with notable neuropsychiatric phenotypes. Together, our observations indicate that LoF variants in SETD1A cause a range of neurodevelopmental disorders, including schizophrenia. Combining these data with previous common variant evidence, we suggest that epigenetic dysregulation, specifically in the histone H3K4 methylation pathway, is an important mechanism in the pathogenesis of schizophrenia.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Singh T,Kurki MI,Curtis D,Purcell SM,Crooks L,McRae J,Suvisaari J,Chheda H,Blackwood D,Breen G,Pietiläinen O,Gerety SS,Ayub M,Blyth M,Cole T,Collier D,Coomber EL,Craddock N,Daly MJ,Danesh J,DiForti M,Foster A,doi
10.1038/nn.4267subject
Has Abstractpub_date
2016-04-01 00:00:00pages
571-7issue
4eissn
1097-6256issn
1546-1726pii
nn.4267journal_volume
19pub_type
杂志文章abstract：:Unifying principles of movement have emerged from the computational study of motor control. We review several of these principles and show how they apply to processes such as motor planning, control, estimation, prediction and learning. Our goal is to demonstrate how specific models emerging from the computational app...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/81497
更新日期：2000-11-01 00:00:00
abstract：:T cells clear virus from the CNS and dynamically regulate brain functions, including spatial learning, through cytokine signaling. Here we determined whether hippocampal T cells that persist after recovery from infection with West Nile virus (WNV) or Zika virus (ZIKV) impact hippocampal-dependent learning and memory. ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-019-0427-y
更新日期：2019-08-01 00:00:00
abstract：:An unresolved question in neuroscience relates to the extent to which corticothalamocortical circuits emanating from layer 5B are involved in information transfer through the cortical hierarchy. Using a new form of optical imaging in a brain slice preparation, we found that the corticothalamocortical pathway drove rob...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2449
更新日期：2010-01-01 00:00:00
abstract：:A long-standing debate in neuroscience is whether classical and operant conditioning are mechanistically similar or distinct. The feeding behavior of Aplysia provides a model system suitable for addressing this question. Here we report that classical and operant conditioning of feeding behavior differentially modify t...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1593
更新日期：2006-01-01 00:00:00
abstract：:Dendritic spikes signal synaptic integration at remote apical dendritic sites in neocortical pyramidal neurons in vitro. Do dendritic spikes have a salient signaling role under in vivo conditions, where neocortical pyramidal neurons are bombarded with synaptic input? In the present study, levels of synaptic conductanc...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1305
更新日期：2004-09-01 00:00:00
abstract：:Transcriptomic analyses of postmortem brains have begun to elucidate molecular abnormalities in autism spectrum disorder (ASD). However, a crucial pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled global patterns of adenosine-to-inosine (A-to-I) ed...
journal_title：Nature neuroscience
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doi：10.1038/s41593-018-0287-x
更新日期：2019-01-01 00:00:00
abstract：:It is widely held that color and motion are processed by separate parallel pathways in the visual system, but this view is difficult to reconcile with the fact that motion can be detected in equiluminant stimuli that are defined by color alone. To examine the relationship between color and motion, we tested three pati...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/688
更新日期：1998-07-01 00:00:00
abstract：:Multiple protein kinase C (PKC) isozymes are present in neurons, where they regulate a variety of cellular functions. Due to the lack of specific PKC isozyme inhibitors, it remains unknown how PKC acts on its selective target(s) and achieves its specific actions. Here we show that a PKC binding protein, enigma homolog...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1041
更新日期：2003-05-01 00:00:00
abstract：:Leptin regulates energy balance. However, knowledge of the critical intracellular transducers of leptin signaling remains incomplete. We found that Rho-kinase 1 (ROCK1) regulates leptin action on body weight homeostasis by activating JAK2, an initial trigger of leptin receptor signaling. Leptin promoted the physical i...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3207
更新日期：2012-10-01 00:00:00
abstract：:The auditory system encodes sound by decomposing the amplitude signal arriving at the ear into multiple frequency bands whose center frequencies and bandwidths are approximately exponential functions of the distance from the stapes. This organization is thought to result from the adaptation of cochlear mechanisms to t...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn831
更新日期：2002-04-01 00:00:00
abstract：:To investigate the mechanisms of persistent neural activity, we obtained in vivo intracellular recordings from neurons in an oculomotor neural integrator of the goldfish during spontaneous saccades and fixations. Persistent changes in firing rate following saccades were associated with step changes in interspike membr...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/84023
更新日期：2001-02-01 00:00:00
abstract：:Voltage-gated sodium channels (Na(V)) are critical for initiation of action potentials. Heterozygous loss-of-function mutations in Na(V)1.1 channels cause severe myoclonic epilepsy in infancy (SMEI). Homozygous null Scn1a-/- mice developed ataxia and died on postnatal day (P) 15 but could be sustained to P17.5 with ma...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1754
更新日期：2006-09-01 00:00:00
abstract：:The ventral intraparietal area (VIP) receives converging inputs from visual, somatosensory, auditory and vestibular systems that use diverse reference frames to encode sensory information. A key issue is how VIP combines those inputs together. We mapped the visual and tactile receptive fields of multimodal VIP neurons...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1480
更新日期：2005-07-01 00:00:00
abstract：:Parkinson disease is a neurodegenerative disorder whose symptoms are caused by the loss of dopaminergic neurons innervating the striatum. As striatal dopamine levels fall, striatal acetylcholine release rises, exacerbating motor symptoms. This adaptation is commonly attributed to the loss of interneuronal regulation b...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1700
更新日期：2006-06-01 00:00:00
abstract：:The usefulness of genetically encoded probes for optical monitoring of neuronal activity and brain circuits would be greatly advanced by the generation of multiple indicators with non-overlapping color spectra. Most existing indicators are derived from or spectrally convergent on GFP. We generated a bright, red, pH-se...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3126
更新日期：2012-05-27 00:00:00
abstract：:The diseased brain hosts a heterogeneous population of myeloid cells, including parenchymal microglia, perivascular cells, meningeal macrophages and blood-borne monocytes. To date, the different types of brain myeloid cells have been discriminated solely on the basis of their localization, morphology and surface epito...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn.2923
更新日期：2011-09-27 00:00:00
abstract：:The production of hippocampal granule neurons continues throughout adulthood but dramatically decreases in old age. Here we show that reducing corticosteroid levels in aged rats restored the rate of cell proliferation, resulting in increased numbers of new granule neurons. This result indicates that the neuronal precu...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/13197
更新日期：1999-10-01 00:00:00
abstract：:To investigate how the brain combines knowledge with visual processing to locate eye movement targets, we trained monkeys to search for a target defined by a conjunction of color and shape. On successful trials, neurons in the frontal eye field not only discriminated the target from distractors, but also discriminated...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/9205
更新日期：1999-06-01 00:00:00
abstract：:Attention powerfully influences auditory perception, but little is understood about the mechanisms whereby attention sharpens responses to unattended sounds. We used high-resolution surface mapping techniques (using functional magnetic resonance imaging, fMRI) to examine activity in human auditory cortex during an int...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1256
更新日期：2004-06-01 00:00:00
abstract：:In severe hypoxia, homeostatic mechanisms maintain function of the brainstem respiratory network. We hypothesized that hypoxia involves a transition from neuronal mechanisms of normal breathing (eupnea) to a rudimentary pattern of inspiratory movements (gasping). We provide evidence for hypoxia-driven transformation w...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1650
更新日期：2006-03-01 00:00:00
abstract：:Angelman syndrome (AS) is a severe neurological disorder characterized by mental retardation, motor dysfunction and epilepsy. We show that the molecular and cellular deficits of an AS mouse model can be rescued by introducing an additional mutation at the inhibitory phosphorylation site of alphaCaMKII. Moreover, these...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1845
更新日期：2007-03-01 00:00:00
abstract：:Although de novo missense mutations have been predicted to account for more cases of autism than gene-truncating mutations, most research has focused on the latter. We identified the properties of de novo missense mutations in patients with neurodevelopmental disorders (NDDs) and highlight 35 genes with excess missens...
journal_title：Nature neuroscience
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更新日期：2017-08-01 00:00:00
abstract：:Interleukin 17 (IL-17) is a signature cytokine of Th17 cells. We previously reported that deletion of NF-κB activator 1 (Act1), the key transducer of IL-17 receptor signaling, from the neuroectodermal lineage in mice (neurons, oligodendrocytes and astrocytes) results in attenuated severity of experimental autoimmune e...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3505
更新日期：2013-10-01 00:00:00
abstract：:To investigate synaptic events underlying sensory perception, we made whole-cell membrane potential recordings of barrel cortex neurons in awake mice while recording whisker-related behavior. During quiet periods, we recorded slow, large-amplitude membrane potential changes, which switched during whisking to small, fa...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1690
更新日期：2006-05-01 00:00:00
abstract：:Humans have ~400 intact odorant receptors, but each individual has a unique set of genetic variations that lead to variation in olfactory perception. We used a heterologous assay to determine how often genetic polymorphisms in odorant receptors alter receptor function. We identified agonists for 18 odorant receptors a...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3598
更新日期：2014-01-01 00:00:00
abstract：: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...
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更新日期：2019-03-01 00:00:00
abstract：:En route to their target, pioneering motor growth cones repeatedly encounter choice points at which they make pathway decisions. In the zebrafish mutant unplugged, two of the three segmental motor axons make incorrect decisions at a somitic choice point. Using positional cloning, we show here that unplugged encodes a ...
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更新日期：2004-12-01 00:00:00
abstract：:Many attempts to obtain reliable self-administration behavior by laboratory animals with delta-9-tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana, have been unsuccessful. Because self-administration behavior has been demonstrated in laboratory animals for almost all other psychoactive drugs abused ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/80577
更新日期：2000-11-01 00:00:00
abstract：:Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants, but the mechanisms by which they influence behavior are only partially resolved. Adult hippocampal neurogenesis is necessary for some of the responses to SSRIs, but it is not known whether mature dentate gyrus granule cells (DG GCs) also ...
journal_title：Nature neuroscience
pub_type： 杂志文章
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更新日期：2015-11-01 00:00:00
abstract：:A fundamental assumption in neuroscience is that brain structure determines function. Accordingly, functionally distinct regions of cortex should be structurally distinct in their connections to other areas. We tested this hypothesis in relation to face selectivity in the fusiform gyrus. By using only structural conne...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3001
更新日期：2011-12-25 00:00:00
