Abstract：
:Class I histone deacetylases (HDACs) Hdac1 and Hdac2 can associate together in protein complexes with transcriptional factors such as methyl-CpG-binding protein 2 (MeCP2). Given their high degree of sequence identity, we examined whether Hdac1 and Hdac2 were functionally redundant in mature mouse brain. We demonstrate that postnatal forebrain-specific deletion of both Hdac1 and Hdac2 in mice impacts neuronal survival and results in an excessive grooming phenotype caused by dysregulation of Sap90/Psd95-associated protein 3 (Sapap3; also known as Dlgap3) in striatum. Moreover, Hdac1- and Hdac2-dependent regulation of Sapap3 expression requires MECP2, the gene involved in the pathophysiology of Rett syndrome. We show that postnatal forebrain-specific deletion of Mecp2 causes excessive grooming, which is rescued by restoring striatal Sapap3 expression. Our results provide new insight into the upstream regulation of Sapap3 and establish the essential role of striatal Hdac1, Hdac2 and MeCP2 for suppression of repetitive behaviors.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Mahgoub M,Adachi M,Suzuki K,Liu X,Kavalali ET,Chahrour MH,Monteggia LMdoi
10.1038/nn.4395subject
Has Abstractpub_date
2016-11-01 00:00:00pages
1506-1512issue
11eissn
1097-6256issn
1546-1726pii
nn.4395journal_volume
19pub_type
杂志文章abstract：:We investigated the regulation of T-type channels by Rho-associated kinase (ROCK). Activation of ROCK via the endogenous ligand lysophosphatidic acid (LPA) reversibly inhibited the peak current amplitudes of rat Ca(v)3.1 and Ca(v)3.3 channels without affecting the voltage dependence of activation or inactivation, wher...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1921
更新日期：2007-07-01 00:00:00
abstract：:Rhythmic movements, such as walking, chewing or scratching, are phylogenetically old motor behaviors found in many organisms, ranging from insects to primates. In contrast, discrete movements, such as reaching, grasping or kicking, are behaviors that have reached sophistication primarily in younger species, particular...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1322
更新日期：2004-10-01 00:00:00
abstract：:Synaptic vesicles release neurotransmitter both actively (on stimulation) and spontaneously (at rest). It has been assumed that identical vesicles use both modes of release; however, recent evidence has challenged this view. Using several assays (FM dye imaging, pHluorin imaging and antibody-labeling of synaptotagmin)...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2690
更新日期：2010-12-01 00:00:00
abstract：:Sensory systems create neural representations of environmental stimuli and these representations can be associated with other stimuli through learning. Are spike patterns the neural representations that get directly associated with reinforcement during conditioning? In the moth Manduca sexta, we found that odor presen...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2192
更新日期：2008-10-01 00:00:00
abstract：:Social behaviors recruit multiple cognitive operations that require interactions between cortical and subcortical brain regions. Interareal synchrony may facilitate such interactions between cortical and subcortical neural populations. However, it remains unknown how neurons from different nodes in the social brain ne...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-020-0593-y
更新日期：2020-04-01 00:00:00
abstract：:Although the prefrontal cortex influences motivated behavior, its role in food intake remains unclear. Here, we demonstrate a role for D1-type dopamine receptor-expressing neurons in the medial prefrontal cortex (mPFC) in the regulation of feeding. Food intake increases activity in D1 neurons of the mPFC in mice, and ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3625
更新日期：2014-02-01 00:00:00
abstract：:The C. elegans SAX-3/Robo receptor acts in anterior-posterior, dorsal-ventral and midline guidance decisions. Here we show that SAX-3 signaling involves the C. elegans Enabled protein UNC-34 and an unexpected Netrin-independent function of the Netrin receptor UNC-40/DCC. Genetic interactions with gain- and loss-of-fun...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn956
更新日期：2002-11-01 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：:The molecular mechanisms that activate morphogenesis of cerebral cortex are currently the subject of intensive experimental analysis. Transcription factor genes of the homeobox, basic helix-loop-helix (bHLH) and zinc-finger families have recently been shown to have essential roles in this process. However, the actual ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn892
更新日期：2002-08-01 00:00:00
abstract：:Odor stimulation evokes complex spatiotemporal activity in the olfactory bulb, suggesting that both the identity of activated neurons and the timing of their activity convey information about odors. However, whether and how downstream neurons decipher these temporal patterns remains unknown. We addressed this question...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3407
更新日期：2013-07-01 00:00:00
abstract：:Individuals' risk attitudes are known to guide choices about uncertain options. However, in the presence of others' decisions, these choices can be swayed and manifest as riskier or safer behavior than one would express alone. To test the mechanisms underlying effective social 'nudges' in human decision-making, we use...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4022
更新日期：2015-06-01 00:00:00
abstract：:A fundamental organizing principle of auditory brain circuits is tonotopy, the orderly representation of the sound frequency to which neurons are most sensitive. Tonotopy arises from the coding of frequency along the cochlea and the topographic organization of auditory pathways. The mechanisms that underlie the establ...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn.2332
更新日期：2009-06-01 00:00:00
abstract：:We examined enhancement of synaptic transmission by neurotrophins at the presynaptic level. In a synaptosomal preparation, brain-derived neurotrophic factor (BDNF) increased mitogen-activated protein (MAP) kinase-dependent synapsin I phosphorylation and acutely facilitated evoked glutamate release. PD98059, used to in...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/73888
更新日期：2000-04-01 00:00:00
abstract：:Sustained activity encoding visual working memory representations has been observed in several cortical areas of primates. Where along the visual pathways this activity emerges remains unknown. Here we show in macaques that sustained spiking activity encoding memorized visual motion directions is absent in direction-s...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3785
更新日期：2014-09-01 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 healthy human brain is a mosaic of varied genomes. Long interspersed element-1 (LINE-1 or L1) retrotransposition is known to create mosaicism by inserting L1 sequences into new locations of somatic cell genomes. Using a machine learning-based, single-cell sequencing approach, we discovered that somatic L1-associat...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4388
更新日期：2016-12-01 00:00:00
abstract：:Hippocampal replay during sharp-wave ripple events (SWRs) is thought to drive memory consolidation in hippocampal and cortical circuits. Changes in neocortical activity can precede SWR events, but whether and how these changes influence the content of replay remains unknown. Here we show that during sleep there is a r...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4457
更新日期：2017-02-01 00:00:00
abstract：:Trial-to-trial variability in the blood oxygen level-dependent (BOLD) response of functional magnetic resonance imaging has been shown to be relevant to human perception and behavior, but the sources of this variability remain unknown. We demonstrate that coherent spontaneous fluctuations in human brain activity accou...
journal_title：Nature neuroscience
pub_type： 临床试验,杂志文章
doi：10.1038/nn1616
更新日期：2006-01-01 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：:Motion and stereoscopic depth are fundamental parameters of the structural analysis of visual scenes. Because they are defined by a difference in object position, either over time or across the eyes, a common neural machinery may be used for encoding these attributes. To examine this idea, we analyzed responses of bin...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/87462
更新日期：2001-05-01 00:00:00
abstract：:Repeated cocaine administration increases the dendritic arborization of nucleus accumbens neurons, but the underlying signaling events remain unknown. Here we show that repeated exposure to cocaine negatively regulates the active form of Rac1, a small GTPase that controls actin remodeling in other systems. Further, we...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3094
更新日期：2012-06-01 00:00:00
abstract：:Uncovering structural regularities and architectural topologies of cortical circuitry is vital for understanding neural computations. Recently, an experimentally constrained algorithm generated a dense network reconstruction of a ∼0.3-mm3 volume from juvenile rat somatosensory neocortex, comprising ∼31,000 cells and ∼...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4576
更新日期：2017-07-01 00:00:00
abstract：:Relative quiescence and self renewal are defining features of adult stem cells, but their potential coordination remains unclear. Subependymal neural stem cells (NSCs) lacking cyclin-dependent kinase (CDK) inhibitor (CKI) 1a (p21) exhibit rapid expansion that is followed by their permanent loss later in life. Here we ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3545
更新日期：2013-11-01 00:00:00
abstract：:Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-018-0119-z
更新日期：2018-05-01 00:00:00
abstract：:Phasic activation of the dopamine (DA) midbrain system in response to unexpected reward or novelty is critical for adaptive behavioral strategies. This activation of DA midbrain neurons occurs via a synaptically triggered switch from low-frequency background spiking to transient high-frequency burst firing. We found t...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3185
更新日期：2012-09-01 00:00:00
abstract：:Neurons in thalamorecipient layers of sensory cortices integrate thalamocortical and intracortical inputs. Although we know that their functional properties can arise from the convergence of thalamic inputs, intracortical circuits could also be involved in thalamocortical transformations of sensory information. We sil...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3494
更新日期：2013-09-01 00:00:00
abstract：:The classic 'size principle' of motor control describes how increasingly forceful movements arise by the recruitment of motoneurons of progressively larger size and force output into the active pool. We explored the activity of pools of spinal interneurons in larval zebrafish and found that increases in swimming speed...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2225
更新日期：2008-12-01 00:00:00
abstract：:Grid cells in layer II of the medial entorhinal cortex form a principal component of the mammalian neural representation of space. The firing pattern of a single grid cell has been hypothesized to be generated through attractor dynamics in a network with a specific local connectivity including both excitatory and inhi...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3310
更新日期：2013-03-01 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：:Neuronal migration disorders such as lissencephaly and subcortical band heterotopia are associated with epilepsy and intellectual disability. DCX, PAFAH1B1 and TUBA1A are mutated in these disorders; however, corresponding mouse mutants do not show heterotopic neurons in the neocortex. In contrast, spontaneously arisen...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3729
更新日期：2014-07-01 00:00:00
