Abstract：
:Mutations in MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT). The RTT missense MECP2R306C mutation prevents MeCP2 from interacting with the NCoR/histone deacetylase 3 (HDAC3) complex; however, the neuronal function of HDAC3 is incompletely understood. We found that neuronal deletion of Hdac3 in mice elicited abnormal locomotor coordination, sociability and cognition. Transcriptional and chromatin profiling revealed that HDAC3 positively regulated a subset of genes and was recruited to active gene promoters via MeCP2. HDAC3-associated promoters were enriched for the FOXO transcription factors, and FOXO acetylation was elevated in Hdac3 knockout (KO) and Mecp2 KO neurons. Human RTT-patient-derived MECP2R306C neural progenitor cells had deficits in HDAC3 and FOXO recruitment and gene expression. Gene editing of MECP2R306C cells to generate isogenic controls rescued HDAC3-FOXO-mediated impairments in gene expression. Our data suggest that HDAC3 interaction with MeCP2 positively regulates a subset of neuronal genes through FOXO deacetylation, and disruption of HDAC3 contributes to cognitive and social impairment.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Nott A,Cheng J,Gao F,Lin YT,Gjoneska E,Ko T,Minhas P,Zamudio AV,Meng J,Zhang F,Jin P,Tsai LHdoi
10.1038/nn.4347subject
Has Abstractpub_date
2016-11-01 00:00:00pages
1497-1505issue
11eissn
1097-6256issn
1546-1726pii
nn.4347journal_volume
19pub_type
杂志文章abstract：:The hippocampus is thought to be involved in episodic memory formation by reactivating traces of waking experience during sleep. Indeed, the joint firing of spatially tuned pyramidal cells encoding nearby places recur during sleep. We found that the sleep cofiring of rat CA1 pyramidal cells encoding similar places inc...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn2037
更新日期：2008-02-01 00:00:00
abstract：:Blood flow into the brain is dynamically regulated to satisfy the changing metabolic requirements of neurons, but how this is accomplished has remained unclear. Here we demonstrate a central role for capillary endothelial cells in sensing neural activity and communicating it to upstream arterioles in the form of an el...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4533
更新日期：2017-05-01 00:00:00
abstract：:Neuroimaging studies show that the efficacy of long-term memory encoding of a stimulus is indexed by transient neural activity elicited by that stimulus. Here, we show that successful memory encoding is also indexed by neural activity that is tonically maintained throughout a study task. Using functional magnetic reso...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn967
更新日期：2002-12-01 00:00:00
abstract：:Neural activity exhibits complex dynamics related to various brain functions, internal states and behaviors. Understanding how neural dynamics explain specific measured behaviors requires dissociating behaviorally relevant and irrelevant dynamics, which is not achieved with current neural dynamic models as they are le...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-020-00733-0
更新日期：2021-01-01 00:00:00
abstract：:In mammals, many daily cycles are driven by a central circadian clock, which is based on the cell-autonomous rhythmic expression of clock genes. It is not clear, however, how peripheral cells are able to interpret the rhythmic signals disseminated from this central oscillator. Here we show that cycling expression of t...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn806
更新日期：2002-03-01 00:00:00
abstract：:Cocaine is a widely abused substance with psychostimulant effects that are attributed to inhibition of the dopamine transporter (DAT). We present molecular models for DAT binding of cocaine and cocaine analogs constructed from the high-resolution structure of the bacterial transporter homolog LeuT. Our models suggest ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2146
更新日期：2008-07-01 00:00:00
abstract：:Three families of ligand-activated ion channels mediate synaptic communication between excitable cells in mammals. For pentameric channels related to nicotinic acetylcholine receptors and tetrameric channels such as glutamate receptors, the pore-forming and gate regions have been studied extensively. In contrast, litt...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2151
更新日期：2008-08-01 00:00:00
abstract：:Long-term synaptic changes, which are essential for learning and memory, are dependent on homeostatic mechanisms that stabilize neural activity. Homeostatic responses have also been implicated in pathological conditions, including nicotine addiction. Although multiple homeostatic pathways have been described, little i...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2969
更新日期：2011-11-13 00:00:00
abstract：:Sharp wave-ripple (SPW-R) complexes in the hippocampus-entorhinal cortex are believed to be important for transferring labile memories from the hippocampus to the neocortex for long-term storage. We found that selective elimination of SPW-Rs during post-training consolidation periods resulted in performance impairment...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2384
更新日期：2009-10-01 00:00:00
abstract：:Memory is supported by a specific ensemble of neurons distributed in the brain that form a unique memory trace. We previously showed that neurons in the lateral amygdala expressing elevated levels of cAMP response-element binding protein are preferentially recruited into fear memory traces and are necessary for the ex...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3592
更新日期：2014-01-01 00:00:00
abstract：:Learning and memory are associated with the formation and modification of neuronal assemblies: populations of neurons that encode what has been learned and mediate memory retrieval upon recall. Functional studies of neuronal assemblies have progressed dramatically thanks to recent technological advances. Here we discu...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn.4418
更新日期：2016-12-01 00:00:00
abstract：:The output of cortical columns is routed to different downstream targets via distinct pathways: cortico-cortical and cortico-subcortical. It is as yet unclear what roles these pathways play in perception, and which cellular and circuit mechanisms regulate their gating. We recently showed that activation of the apical ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-020-0677-8
更新日期：2020-10-01 00:00:00
abstract：:Major, rapid performance improvements in perceptual training are often dismissed as 'task' or 'procedural' learning because they are fast and generalize within a task. We assessed the contributions of perceptual and procedural learning to improvement in an auditory tone frequency learning task in humans and found that...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1315
更新日期：2004-10-01 00:00:00
abstract：:Forces developed by cochlear outer hair cells (OHCs) are responsible for the sharp tuning that underlies sensitivity and frequency selectivity in the ear. OHCs exhibit a voltage-dependent motility involving a 'motor' protein embedded in the basolateral membrane. The motor has so far resisted molecular identification. ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/11174
更新日期：1999-08-01 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Nature neuroscience
pub_type： 已发布勘误
doi：10.1038/s41593-019-0546-5
更新日期：2019-12-01 00:00:00
abstract：:We show that a natural behavior, exploration of a novel environment, causes DNA double-strand breaks (DSBs) in neurons of young adult wild-type mice. DSBs occurred in multiple brain regions, were most abundant in the dentate gyrus, which is involved in learning and memory, and were repaired within 24 h. Increasing neu...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3356
更新日期：2013-05-01 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：:Experience-dependent plasticity in adult visual cortex is believed to have important roles in visual coding and perceptual learning. Here we show that repeated stimulation with movies of natural scenes induces a rapid improvement in response reliability in cat visual cortex, whereas stimulation with white noise or fla...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1895
更新日期：2007-06-01 00:00:00
abstract：:Calcium arising through release from intracellular stores and from influx across the plasma membrane is essential for signalling by specific guidance cues and by factors that inhibit axon regeneration. The mediators of calcium influx in these cases are largely unknown. Transient receptor potential channels (TRPCs) bel...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1459
更新日期：2005-06-01 00:00:00
abstract：:Adult neurogenesis occurs in the hippocampus and the olfactory bulb of the mammalian CNS. Recent studies have demonstrated that newborn granule cells of the adult hippocampus are postsynaptic targets of excitatory and inhibitory neurons, but evidence of synapse formation by the axons of these cells is still lacking. B...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2156
更新日期：2008-08-01 00:00:00
abstract：:Laboratory models, including animal tissues and live animals, have proven useful for discovery of molecular targets of alcohol action as well as for characterization of genetic and environmental factors that influence alcohol's neural actions. Here we consider strengths and weaknesses of laboratory models used in alco...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn1581
更新日期：2005-11-01 00:00:00
abstract：: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 com...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-018-0317-8
更新日期：2019-03-01 00:00:00
abstract：:In the postnatal subventricular zone (SVZ), local cues or signaling molecules released from neuroblasts limit the proliferation of glial fibrillary acidic protein (GFAP)-expressing progenitors thought to be stem cells. However, signals between SVZ cells have not been identified. We show that depolarization of neurobla...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1522
更新日期：2005-09-01 00:00:00
abstract：:Though motor neurons selectively degenerate in amyotrophic lateral sclerosis, other cell types are likely involved in this disease. We recently generated rNLS8 mice in which human TDP-43 (hTDP-43) pathology could be reversibly induced in neurons and expected that microglia would contribute to neurodegeneration. Howeve...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-018-0083-7
更新日期：2018-03-01 00:00:00
abstract：:Processing of rapidly successive acoustic stimuli can be markedly improved by sensory training. To investigate the cortical mechanisms underlying such temporal plasticity, we trained rats in a 'sound maze' in which navigation using only auditory cues led to a target location paired with food reward. In this task, the ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1293
更新日期：2004-09-01 00:00:00
abstract：:Sensory pathways are typically studied by starting at receptor neurons and following postsynaptic neurons into the brain. However, this leads to a bias in analyses of activity toward the earliest layers of processing. Here, we present new methods for volumetric neural imaging with precise across-brain registration to ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-020-00743-y
更新日期：2021-01-01 00:00:00
abstract：:Endogenous cannabinoids (eCB) mediate synaptic plasticity in brain regions involved in learning and reward. Here we show that in mice, a single in-vivo exposure to Delta 9-tetrahydrocannabinol (THC) abolishes the retrograde signaling that underlies eCB-mediated synaptic plasticity in both nucleus accumbens (NAc) and h...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1251
更新日期：2004-06-01 00:00:00
abstract：:We combined psychophysical and transcranial magnetic stimulation studies to investigate the dynamics of action anticipation and its underlying neural correlates in professional basketball players. Athletes predicted the success of free shots at a basket earlier and more accurately than did individuals with comparable ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2182
更新日期：2008-09-01 00:00:00
abstract：:Neuroinflammatory diseases, such as multiple sclerosis, are characterized by invasion of the brain by autoreactive T cells. The mechanism for how T cells acquire their encephalitogenic phenotype and trigger disease remains, however, unclear. The existence of lymphatic vessels in the meninges indicates a relevant link ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-018-0227-9
更新日期：2018-10-01 00:00:00
abstract：:Deciphering the interneuronal circuitry is central to understanding brain functions, yet it remains a challenging task in neurobiology. Using simultaneous quadruple-octuple in vitro and dual in vivo whole-cell recordings, we found two previously unknown interneuronal circuits that link cortical layer 1-3 (L1-3) intern...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3305
更新日期：2013-02-01 00:00:00
