Journal ArticleBiol Psychiatry · November 1, 2024
BACKGROUND: Experience-dependent functional adaptation of nucleus accumbens (NAc) circuitry underlies the development and expression of reward-motivated behaviors. Parvalbumin-expressing GABAergic (gamma-aminobutyric acidergic) interneurons (PVINs) within ...
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Journal ArticleNeuron · September 25, 2024
Neuronal activity-regulated gene expression plays a crucial role in sculpting neural circuits that underpin adaptive brain function. Transcriptional enhancers are now recognized as key components of gene regulation that orchestrate spatiotemporally precise ...
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Journal ArticleCurr Opin Neurobiol · September 14, 2024
Epigenetic regulation of the genome is required for cell-type differentiation during organismal development and is especially important to generate the panoply of specialized cell types that comprise the brain. Here, we review how progressive changes in th ...
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Journal ArticleBMC Biol · September 2, 2024
BACKGROUND: The Zic family of transcription factors (TFs) promote both proliferation and maturation of cerebellar granule neurons (CGNs), raising the question of how a single, constitutively expressed TF family can support distinct developmental processes. ...
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Journal ArticlebioRxiv · January 4, 2024
BACKGROUND: The Zic family of transcription factors (TFs) promote both proliferation and maturation of cerebellar granule neurons (CGNs), raising the question of how a single, constitutively expressed TF family can support distinct developmental processes. ...
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Journal ArticleBiol Psychiatry Glob Open Sci · October 2023
BACKGROUND: Glutamatergic projection neurons of the lateral habenula (LHb) drive behavioral state modulation by regulating the activity of midbrain monoaminergic neurons. Identifying circuit mechanisms that modulate LHb output is of interest for understand ...
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Journal ArticleGenes Dev · October 1, 2023
Mutations in the methyl-DNA binding domain of MECP2 cause Rett syndrome; however, distinct mutations are associated with different severity of the disease. Live-cell imaging and single-molecule tracking are sensitive methods to quantify the DNA binding aff ...
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Journal ArticleMol Psychiatry · August 2023
Parvalbumin-expressing (PV+) interneurons of the nucleus accumbens (NAc) play an essential role in the addictive-like behaviors induced by psychostimulant exposure. To identify molecular mechanisms of PV+ neuron plasticity, we isolated interneuron nuclei f ...
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Journal ArticleElife · April 24, 2023
The functional maturation of neurons is a prolonged process that extends past the mitotic exit and is mediated by the chromatin-dependent orchestration of gene transcription programs. We find that expression of this maturation gene program in mouse cerebel ...
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Journal ArticlebioRxiv · January 9, 2023
Glutamatergic projection neurons of the lateral habenula (LHb) drive behavioral state modulation by regulating the activity of midbrain monoaminergic neurons. Identifying circuit mechanisms that modulate LHb output is of interest for understanding control ...
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Journal ArticleHum Mol Genet · May 4, 2022
Rahman syndrome (RMNS) is a rare genetic disorder characterized by mild to severe intellectual disability, hypotonia, anxiety, autism spectrum disorder, vision problems, bone abnormalities and dysmorphic facies. RMNS is caused by de novo heterozygous mutat ...
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Journal ArticleNat Methods · August 2021
CRISPR-Cas9 technologies have dramatically increased the ease of targeting DNA sequences in the genomes of living systems. The fusion of chromatin-modifying domains to nuclease-deactivated Cas9 (dCas9) has enabled targeted epigenome editing in both culture ...
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Journal ArticleJ Vis Exp · June 9, 2021
Neurons undergo dynamic changes in their structure and function during brain development to form appropriate connections with other cells. The rodent cerebellum is an ideal system to track the development and morphogenesis of a single cell type, the cerebe ...
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Journal ArticleCell Calcium · January 2021
It is a striking paradox that the activation of NMDA-type glutamate receptors (NMDARs) can both promote neuronal survival and induce excitotoxic cell death. Yet the molecular mechanisms that distinguish these cellular consequences have remained obscure. A ...
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Journal ArticleJ Biol Chem · June 19, 2020
N-Methyl-d-aspartate type glutamate receptors (NMDARs) are key mediators of synaptic activity-regulated gene transcription in neurons, both during development and in the adult brain. Developmental differences in the glutamate receptor ionotropic NMDA 2 (Gl ...
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Journal ArticleNat Neurosci · January 2020
Transcriptional enhancers are regulatory DNA elements that underlie the specificity and dynamic patterns of gene expression. Over the past decade, large-scale functional genomics projects have driven transformative progress in our understanding of enhancer ...
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Journal ArticleCurr Opin Neurobiol · December 2019
For more than 40 years after its discovery, histone methylation was thought to be largely irreversible. However, the first histone demethylase (HDM) was identified in 2004, challenging this notion. Since that time, more than 20 HDMs have been identified an ...
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Journal ArticleNeuron · November 20, 2019
A new study in Cell (Brigidi et al., 2019) shows that local dendritic versus somatic translation of the neuronal activity-inducible transcription factor NPAS4 drives the formation of distinct heterodimers that enable stimulus-specificity to be encoded into ...
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Journal ArticleBiol Psychiatry · November 1, 2024
BACKGROUND: Experience-dependent functional adaptation of nucleus accumbens (NAc) circuitry underlies the development and expression of reward-motivated behaviors. Parvalbumin-expressing GABAergic (gamma-aminobutyric acidergic) interneurons (PVINs) within ...
Full textLink to itemCite
Journal ArticleNeuron · September 25, 2024
Neuronal activity-regulated gene expression plays a crucial role in sculpting neural circuits that underpin adaptive brain function. Transcriptional enhancers are now recognized as key components of gene regulation that orchestrate spatiotemporally precise ...
Full textLink to itemCite
Journal ArticleCurr Opin Neurobiol · September 14, 2024
Epigenetic regulation of the genome is required for cell-type differentiation during organismal development and is especially important to generate the panoply of specialized cell types that comprise the brain. Here, we review how progressive changes in th ...
Full textLink to itemCite
Journal ArticleBMC Biol · September 2, 2024
BACKGROUND: The Zic family of transcription factors (TFs) promote both proliferation and maturation of cerebellar granule neurons (CGNs), raising the question of how a single, constitutively expressed TF family can support distinct developmental processes. ...
Full textLink to itemCite
Journal ArticlebioRxiv · January 4, 2024
BACKGROUND: The Zic family of transcription factors (TFs) promote both proliferation and maturation of cerebellar granule neurons (CGNs), raising the question of how a single, constitutively expressed TF family can support distinct developmental processes. ...
Full textLink to itemCite
Journal ArticleBiol Psychiatry Glob Open Sci · October 2023
BACKGROUND: Glutamatergic projection neurons of the lateral habenula (LHb) drive behavioral state modulation by regulating the activity of midbrain monoaminergic neurons. Identifying circuit mechanisms that modulate LHb output is of interest for understand ...
Full textLink to itemCite
Journal ArticleGenes Dev · October 1, 2023
Mutations in the methyl-DNA binding domain of MECP2 cause Rett syndrome; however, distinct mutations are associated with different severity of the disease. Live-cell imaging and single-molecule tracking are sensitive methods to quantify the DNA binding aff ...
Full textLink to itemCite
Journal ArticleMol Psychiatry · August 2023
Parvalbumin-expressing (PV+) interneurons of the nucleus accumbens (NAc) play an essential role in the addictive-like behaviors induced by psychostimulant exposure. To identify molecular mechanisms of PV+ neuron plasticity, we isolated interneuron nuclei f ...
Full textLink to itemCite
Journal ArticleElife · April 24, 2023
The functional maturation of neurons is a prolonged process that extends past the mitotic exit and is mediated by the chromatin-dependent orchestration of gene transcription programs. We find that expression of this maturation gene program in mouse cerebel ...
Full textLink to itemCite
Journal ArticlebioRxiv · January 9, 2023
Glutamatergic projection neurons of the lateral habenula (LHb) drive behavioral state modulation by regulating the activity of midbrain monoaminergic neurons. Identifying circuit mechanisms that modulate LHb output is of interest for understanding control ...
Full textLink to itemCite
Journal ArticleHum Mol Genet · May 4, 2022
Rahman syndrome (RMNS) is a rare genetic disorder characterized by mild to severe intellectual disability, hypotonia, anxiety, autism spectrum disorder, vision problems, bone abnormalities and dysmorphic facies. RMNS is caused by de novo heterozygous mutat ...
Full textLink to itemCite
Journal ArticleNat Methods · August 2021
CRISPR-Cas9 technologies have dramatically increased the ease of targeting DNA sequences in the genomes of living systems. The fusion of chromatin-modifying domains to nuclease-deactivated Cas9 (dCas9) has enabled targeted epigenome editing in both culture ...
Full textLink to itemCite
Journal ArticleJ Vis Exp · June 9, 2021
Neurons undergo dynamic changes in their structure and function during brain development to form appropriate connections with other cells. The rodent cerebellum is an ideal system to track the development and morphogenesis of a single cell type, the cerebe ...
Full textLink to itemCite
Journal ArticleCell Calcium · January 2021
It is a striking paradox that the activation of NMDA-type glutamate receptors (NMDARs) can both promote neuronal survival and induce excitotoxic cell death. Yet the molecular mechanisms that distinguish these cellular consequences have remained obscure. A ...
Full textLink to itemCite
Journal ArticleJ Biol Chem · June 19, 2020
N-Methyl-d-aspartate type glutamate receptors (NMDARs) are key mediators of synaptic activity-regulated gene transcription in neurons, both during development and in the adult brain. Developmental differences in the glutamate receptor ionotropic NMDA 2 (Gl ...
Full textOpen AccessLink to itemCite
Journal ArticleNat Neurosci · January 2020
Transcriptional enhancers are regulatory DNA elements that underlie the specificity and dynamic patterns of gene expression. Over the past decade, large-scale functional genomics projects have driven transformative progress in our understanding of enhancer ...
Full textLink to itemCite
Journal ArticleCurr Opin Neurobiol · December 2019
For more than 40 years after its discovery, histone methylation was thought to be largely irreversible. However, the first histone demethylase (HDM) was identified in 2004, challenging this notion. Since that time, more than 20 HDMs have been identified an ...
Full textLink to itemCite
Journal ArticleNeuron · November 20, 2019
A new study in Cell (Brigidi et al., 2019) shows that local dendritic versus somatic translation of the neuronal activity-inducible transcription factor NPAS4 drives the formation of distinct heterodimers that enable stimulus-specificity to be encoded into ...
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Journal ArticleTrends Neurosci · September 2019
Whether dynamic changes in genome architecture underlie transcriptional and functional plasticity in mature neurons has been technically challenging to address. A recent study (Yamada et al., Nature, 2019) exploited experimental advantages of the cerebellu ...
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Journal ArticleNat Commun · June 20, 2019
Most adaptive behaviors require precise tracking of targets in space. In pursuit behavior with a moving target, mice use distance to target to guide their own movement continuously. Here, we show that in the sensorimotor striatum, parvalbumin-positive fast ...
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Journal ArticleCell Rep · January 29, 2019
Neuronal activity-inducible gene transcription correlates with rapid and transient increases in histone acetylation at promoters and enhancers of activity-regulated genes. Exactly how histone acetylation modulates transcription of these genes has remained ...
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Journal ArticleTrends Neurosci · May 2018
Neurons are dynamic cells that respond and adapt to stimuli throughout their long postmitotic lives. The structural and functional plasticity of neurons requires the regulated transcription of new gene products, and dysregulation of transcription in either ...
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Journal ArticleNeuropsychopharmacology · April 2018
To determine the requirement for parvalbumin (PV) expressing GABAergic interneurons of the nucleus accumbens (NAc) in the behavioral adaptations induced by amphetamine (AMPH), we blocked synaptic vesicle release from these neurons using Cre-inducible viral ...
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Journal ArticleMol Cell Neurosci · March 2018
The histone H3 lysine 27 (H3K27) demethylase Kdm6b (Jmjd3) can promote cellular differentiation, however its physiological functions in neurons remain to be fully determined. We studied the expression and function of Kdm6b in differentiating granule neuron ...
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Journal ArticleGenome Biol · September 4, 2017
Single-molecule RNA fluorescence in situ hybridization (smFISH) provides unparalleled resolution in the measurement of the abundance and localization of nascent and mature RNA transcripts in fixed, single cells. We developed a computational pipeline (BayFi ...
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Journal ArticleJ Neurophysiol · August 1, 2017
The wiring of synaptic connections in the developing mammalian brain is shaped by both intrinsic and extrinsic signals. One point where these regulatory pathways converge is via the sensory experience-dependent regulation of new gene transcription. Recent ...
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Journal ArticlePsychopharmacology (Berl) · March 2017
RATIONALE: Phosphorylation of the methyl DNA-binding protein MeCP2 at Ser421 (pMeCP2-S421) is induced in corticolimbic brain regions during exposure to drugs of abuse and modulates reward-driven behaviors. However, whether pMeCP2-S421 is also involved in b ...
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Journal ArticleYale J Biol Med · December 2016
The dynamic orchestration of gene expression is crucial for the proper differentiation, function, and adaptation of cells. In the brain, transcriptional regulation underlies the incredible diversity of neuronal cell types and contributes to the ability of ...
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Journal ArticleJ Neurochem · April 2016
Neuronal activity sculpts brain development by inducing the transcription of genes such as brain-derived neurotrophic factor (Bdnf) that modulate the function of synapses. Sensory experience is transduced into changes in gene transcription via the activati ...
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Journal ArticleJ Neurosci · October 14, 2015
UNLABELLED: Sprinkled throughout the genome are a million regulatory sequences called transcriptional enhancers that activate gene promoters in the right cells, at the right time. Enhancers endow the brain with its incredible diversity of cell types and al ...
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Journal ArticleJ Biol Chem · May 29, 2015
Mutations in PARKIN (PARK2), an ubiquitin ligase, cause early onset Parkinson disease. Parkin was shown to bind, ubiquitinate, and target depolarized mitochondria for destruction by autophagy. This process, mitophagy, is considered crucial for maintaining ...
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Journal ArticleNat Neurosci · May 2015
To identify chromatin mechanisms of neuronal differentiation, we characterized chromatin accessibility and gene expression in cerebellar granule neurons (CGNs) of the developing mouse. We used DNase-seq to map accessibility of cis-regulatory elements and R ...
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Journal ArticleScience · December 12, 2014
Songbirds represent an important model organism for elucidating molecular mechanisms that link genes with complex behaviors, in part because they have discrete vocal learning circuits that have parallels with those that mediate human speech. We found that ...
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Journal ArticleMol Cell Neurosci · July 2014
Enzymes that regulate histone lysine methylation play important roles in neuronal differentiation, but little is known about their contributions to activity-regulated gene transcription in differentiated neurons. We characterized activity-regulated express ...
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Journal ArticleNeuroscience · April 4, 2014
The human brain has a remarkable capacity to adapt to and learn from a wide range of variations in the environment. However, environmental challenges can also precipitate psychiatric disorders in susceptible individuals. Why any given experience should ind ...
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Journal ArticleJ Neurosci · March 26, 2014
The methyl-DNA binding protein MeCP2 is emerging as an important regulator of drug reinforcement processes. Psychostimulants induce phosphorylation of MeCP2 at Ser421; however, the functional significance of this posttranslational modification for addictiv ...
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Journal ArticleJ Neurosci · January 15, 2014
We have previously shown that the botanical drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, provides neuroprotection in both in vitro and in vivo brain slice-based models for focal ischemia (Dunn et al., 2011). Intriguingly, plasm ...
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Journal ArticleJ Neurosci · January 8, 2014
A key feature of the CNS is structural plasticity, the ability of neurons to alter their morphology and connectivity in response to sensory experience and other changes in the environment. How this structural plasticity is achieved at the molecular level i ...
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Journal ArticleHandb Exp Pharmacol · 2014
Neurotrophins are powerful molecules. Small quantities of these secreted proteins exert robust effects on neuronal survival, synapse stabilization, and synaptic function. Key functions of the neurotrophins rely on these proteins being expressed at the righ ...
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Journal ArticleGenes Brain Behav · August 2013
Interval timing within the seconds-to-minutes range involves the interaction of the prefrontal cortex and basal ganglia via dopaminergic-glutamatergic pathways. Because the secreted protein brain-derived neurotrophic factor (BDNF) is able to modulate dopam ...
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Journal ArticleCold Spring Harb Perspect Med · March 1, 2013
Chronic drug exposure alters gene expression in the brain and produces long-term changes in neural networks that underlie compulsive drug taking and seeking. Exactly how drug-induced changes in synaptic plasticity and subsequent gene expression are transla ...
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Journal ArticleMol Ther · January 2013
Typical Rett syndrome (RTT) is a pediatric disorder caused by loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. The demonstrated reversibility of RTT-like phenotypes in mice suggests that MECP2 gene replacement is a potential the ...
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Journal ArticleJ Neurosci · October 10, 2012
Although tricyclic antidepressants rapidly activate monoaminergic neurotransmission, these drugs must be administered chronically to alleviate symptoms of depression. This observation suggests that molecular mechanisms downstream of monoamine receptor acti ...
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Journal ArticleJ Neurosci · September 12, 2012
Transcription of the gene encoding brain-derived neurotropic factor (BDNF) is induced in response to a wide variety of extracellular stimuli via the activation of a complex array of transcription factors. However, to what degree individual transcription fa ...
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Journal ArticleEpigenetics · February 2012
Loss-of-function mutations in the methyl-DNA binding protein MeCP2 are associated with neurological dysfunction and impaired neural plasticity. However, the transcriptional changes that underlie these deficits remain poorly understood. Here, we show that m ...
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Journal ArticleNeuron · January 12, 2012
The histone deacetylase HDAC5 has been shown to regulate behavioral adaptations to cocaine. In this issue of Neuron, Taniguchi et al. (2012) describe a cAMP-dependent signaling pathway that regulates nuclear accumulation of HDAC5, suggesting a mechanism to ...
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Journal ArticleBiomedical Optics, BIOMED 2012 · January 1, 2012
We present live cell imaging using spectral-domain differential interference contrast microscopy, a novel technique for high-resolution, quantitative measurement of optical pathlength gradients. Imaging and dynamic monitoring of live neurons and cardiomyoc ...
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Journal ArticleNeuropsychopharmacology · January 2012
Systemic administration of amphetamine (AMPH) induces phosphorylation of MeCP2 at Ser421 (pMeCP2) in select populations of neurons in the mesolimbocortical brain regions. Because AMPH simultaneously activates multiple monoamine neurotransmitter systems, he ...
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Journal ArticleNeuron · October 6, 2011
Autism spectrum disorders such as Rett syndrome (RTT) have been hypothesized to arise from defects in experience-dependent synapse maturation. RTT is caused by mutations in MECP2, a nuclear protein that becomes phosphorylated at S421 in response to neurona ...
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Journal ArticleProg Neurobiol · August 2011
The brain is a highly adaptable organ that is capable of converting sensory information into changes in neuronal function. This plasticity allows behavior to be accommodated to the environment, providing an important evolutionary advantage. Neurons convert ...
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Journal ArticleCold Spring Harb Perspect Biol · June 1, 2011
Activity-dependent plasticity of vertebrate neurons allows the brain to respond to its environment. During brain development, both spontaneous and sensory-driven neural activity are essential for instructively guiding the process of synapse development. Th ...
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Journal ArticleCell Calcium · May 2011
Calcium-response factor (CaRF) is a unique DNA-binding protein first recognized as a transcription factor for its role in modulating transcription of the gene encoding Brain-Derived Neurotrophic Factor (BDNF) in neurons. Here I review evidence for the biol ...
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Journal ArticleNat Neurosci · September 2010
MeCP2 is a methyl DNA-binding transcriptional regulator that contributes to the development and function of CNS synapses; however, the requirement for MeCP2 in stimulus-regulated behavioral plasticity is not fully understood. Here we show that acute viral ...
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Journal ArticleJ Neurosci · June 2, 2010
Transcription factors are a key point of convergence between the cell-intrinsic and extracellular signals that guide synaptic development and brain plasticity. Calcium-response factor (CaRF) is a unique transcription factor first identified as a binding pr ...
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Journal ArticlePLoS One · May 27, 2010
Calcium-Response Factor (CaRF) was first identified as a transcription factor based on its affinity for a neuronal-selective calcium-response element (CaRE1) in the gene encoding Brain-Derived Neurotrophic Factor (BDNF). However, because CaRF shares no hom ...
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Journal ArticlePLoS ONE · 2010
Calcium-Response Factor (CaRF) was first identified as a transcription factor based on its affinity for a neuronal-selective calcium-response element (CaRE1) in the gene encoding Brain-Derived Neurotrophic Factor (BDNF). However, because CaRF shares no hom ...
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Journal ArticleJ Neurosci · July 15, 2009
The Ca(2+)/calmodulin-activated kinases CaMKK2 and CaMKIV are highly expressed in the brain where they play important roles in activating intracellular responses to elevated Ca(2+). To address the biological functions of Ca(2+) signaling via these kinases ...
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Journal ArticleNeuron · November 26, 2008
Neuronal activity regulates the transcription of a large set of genes, many of which encode proteins that modify synaptic function. In this issue of Neuron, Hong et al. selectively impair activity-dependent Bdnf transcription and demonstrate that this proc ...
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Journal Article · January 1, 2008
Transcription of Brain-derived neurotrophic factor (Bdnf) is rapidly and robustly induced by neuronal activity, providing a powerful assay for the identification and characterization of neuronal activity-dependent transcriptional mechanisms. The Bdnf gene ...
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Journal ArticleFree Radic Biol Med · January 1, 2006
In Alzheimer's disease (AD), oxidative stress-induced lipid peroxidation leads to accumulation of unsaturated aldehydes including acrolein and 4-hydroxynonenal (4HNE) in brain. In this study, we examined the effects of these lipid peroxidation products on ...
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Journal ArticleCurr Opin Neurobiol · February 2005
Cognitive development is determined by both genetics and environment. One point of convergence of these two influences is the neural activity-dependent regulation of programs of gene expression that specify neuronal fate and function. Human genetic studies ...
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Journal ArticleScience · October 31, 2003
Mutations in MeCP2, which encodes a protein that has been proposed to function as a global transcriptional repressor, are the cause of Rett syndrome (RT T), an X-linked progressive neurological disorder. Although the selective inactivation of MeCP2 in neur ...
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Journal ArticleJ Neurosci · April 1, 2003
To identify molecular mechanisms that control activity-dependent gene expression in the CNS, we have characterized the factors that mediate activity-dependent transcription of BDNF promoter III. We report the identification of a Ca(2+)-responsive E-box ele ...
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Journal ArticleNeuron · January 31, 2002
Transcription of the brain-derived neurotrophic factor (BDNF) gene is regulated in a calcium- and neuron-selective manner; however, the mechanisms that underlie this selectivity are not known. We have characterized a new calcium-response element, CaRE1, th ...
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Journal ArticleProc Natl Acad Sci U S A · September 25, 2001
Plasticity is a remarkable feature of the brain, allowing neuronal structure and function to accommodate to patterns of electrical activity. One component of these long-term changes is the activity-driven induction of new gene expression, which is required ...
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Journal ArticleNat Biotechnol · April 2001
We describe a flexible system for gene expression profiling using arrays of tens of thousands of oligonucleotides synthesized in situ by an ink-jet printing method employing standard phosphoramidite chemistry. We have characterized the dependence of hybrid ...
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Journal ArticleScience · November 12, 1999
A mechanism by which the Ras-mitogen-activated protein kinase (MAPK) signaling pathway mediates growth factor-dependent cell survival was characterized. The MAPK-activated kinases, the Rsks, catalyzed the phosphorylation of the pro-apoptotic protein BAD at ...
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Journal ArticleJ Cell Biol · November 17, 1997
Synaptic vesicles are concentrated in the distal axon, far from the site of protein synthesis. Integral membrane proteins destined for this organelle must therefore make complex targeting decisions. Short amino acid sequences have been shown to act as targ ...
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Journal ArticleJ Neurosci · August 15, 1997
Neurons are highly polarized cells that must sort proteins synthesized in the cell body for transport into the axon or the dendrites. Given the amount of time and energy needed to deliver proteins to the distal processes, neurons must have high fidelity me ...
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