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Anne Elizabeth West

Professor of Neurobiology
Neurobiology
Box 3209, Durham, NC 27710
Bryan Research Building, 311 Research Drive Room 301D, Durham, NC 27710

Selected Publications


The Perineuronal Net Protein Brevican Acts in Nucleus Accumbens Parvalbumin-Expressing Interneurons of Adult Mice to Regulate Excitatory Synaptic Inputs and Motivated Behaviors.

Journal Article Biol 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 text Link to item Cite

Neuronal enhancers fine-tune adaptive circuit plasticity.

Journal Article Neuron · 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 text Link to item Cite

Epigenetics and the timing of neuronal differentiation.

Journal Article Curr 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 text Link to item Cite

Genome binding properties of Zic transcription factors underlie their changing functions during neuronal maturation.

Journal Article BMC 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 text Link to item Cite

Genome binding properties of Zic transcription factors underlie their changing functions during neuronal maturation.

Journal Article bioRxiv · 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 text Link to item Cite

The neuronal epigenome is special.

Journal Article Nat Rev Mol Cell Biol · January 2024 Full text Link to item Cite

Genetics and epigenetics approaches as a path to the future of addiction science.

Journal Article Molecular and cellular neurosciences · December 2023 Full text Open Access Cite

Single-Nucleus Transcriptional Profiling of GAD2-Positive Neurons From Mouse Lateral Habenula Reveals Distinct Expression of Neurotransmission- and Depression-Related Genes.

Journal Article Biol 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 text Link to item Cite

Imaging the binding of MECP2 to DNA.

Journal Article Genes 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 text Link to item Cite

Cell-type specific transcriptional adaptations of nucleus accumbens interneurons to amphetamine.

Journal Article Mol 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 text Link to item Cite

Bidirectional regulation of postmitotic H3K27me3 distributions underlie cerebellar granule neuron maturation dynamics.

Journal Article Elife · 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 text Link to item Cite

Single-nucleus transcriptional profiling of GAD2-positive neurons from mouse lateral habenula reveals distinct expression of neurotransmission- and depression-related genes.

Journal Article bioRxiv · 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 text Link to item Cite

Mutations of the histone linker H1-4 in neurodevelopmental disorders and functional characterization of neurons expressing C-terminus frameshift mutant H1.4.

Journal Article Hum 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 text Link to item Cite

Transgenic mice for in vivo epigenome editing with CRISPR-based systems.

Journal Article Nat 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 text Link to item Cite

Utilizing In Vivo Postnatal Electroporation to Study Cerebellar Granule Neuron Morphology and Synapse Development.

Journal Article J 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 text Link to item Cite

TRPing into excitotoxic neuronal death.

Journal Article Cell 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 text Link to item Cite

The NMDA receptor subunit GluN3A regulates synaptic activity-induced and myocyte enhancer factor 2C (MEF2C)-dependent transcription.

Journal Article J 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 text Open Access Link to item Cite

Neurobiological functions of transcriptional enhancers.

Journal Article Nat 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 text Link to item Cite

Histone demethylases in neuronal differentiation, plasticity, and disease.

Journal Article Curr 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 text Link to item Cite

Activity-Dependent Transcription Collaborates with Local Dendritic Translation to Encode Stimulus-Specificity in the Genome Binding of NPAS4.

Journal Article Neuron · 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 ... Full text Link to item Cite

The Perineuronal Net Protein Brevican Acts in Nucleus Accumbens Parvalbumin-Expressing Interneurons of Adult Mice to Regulate Excitatory Synaptic Inputs and Motivated Behaviors.

Journal Article Biol 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 text Link to item Cite

Neuronal enhancers fine-tune adaptive circuit plasticity.

Journal Article Neuron · 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 text Link to item Cite

Epigenetics and the timing of neuronal differentiation.

Journal Article Curr 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 text Link to item Cite

Genome binding properties of Zic transcription factors underlie their changing functions during neuronal maturation.

Journal Article BMC 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 text Link to item Cite

Genome binding properties of Zic transcription factors underlie their changing functions during neuronal maturation.

Journal Article bioRxiv · 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 text Link to item Cite

The neuronal epigenome is special.

Journal Article Nat Rev Mol Cell Biol · January 2024 Full text Link to item Cite

Genetics and epigenetics approaches as a path to the future of addiction science.

Journal Article Molecular and cellular neurosciences · December 2023 Full text Open Access Cite

Single-Nucleus Transcriptional Profiling of GAD2-Positive Neurons From Mouse Lateral Habenula Reveals Distinct Expression of Neurotransmission- and Depression-Related Genes.

Journal Article Biol 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 text Link to item Cite

Imaging the binding of MECP2 to DNA.

Journal Article Genes 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 text Link to item Cite

Cell-type specific transcriptional adaptations of nucleus accumbens interneurons to amphetamine.

Journal Article Mol 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 text Link to item Cite

Bidirectional regulation of postmitotic H3K27me3 distributions underlie cerebellar granule neuron maturation dynamics.

Journal Article Elife · 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 text Link to item Cite

Single-nucleus transcriptional profiling of GAD2-positive neurons from mouse lateral habenula reveals distinct expression of neurotransmission- and depression-related genes.

Journal Article bioRxiv · 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 text Link to item Cite

Mutations of the histone linker H1-4 in neurodevelopmental disorders and functional characterization of neurons expressing C-terminus frameshift mutant H1.4.

Journal Article Hum 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 text Link to item Cite

Transgenic mice for in vivo epigenome editing with CRISPR-based systems.

Journal Article Nat 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 text Link to item Cite

Utilizing In Vivo Postnatal Electroporation to Study Cerebellar Granule Neuron Morphology and Synapse Development.

Journal Article J 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 text Link to item Cite

TRPing into excitotoxic neuronal death.

Journal Article Cell 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 text Link to item Cite

The NMDA receptor subunit GluN3A regulates synaptic activity-induced and myocyte enhancer factor 2C (MEF2C)-dependent transcription.

Journal Article J 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 text Open Access Link to item Cite

Neurobiological functions of transcriptional enhancers.

Journal Article Nat 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 text Link to item Cite

Histone demethylases in neuronal differentiation, plasticity, and disease.

Journal Article Curr 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 text Link to item Cite

Activity-Dependent Transcription Collaborates with Local Dendritic Translation to Encode Stimulus-Specificity in the Genome Binding of NPAS4.

Journal Article Neuron · 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 ... Full text Link to item Cite

Transcribing Memories in Genome Architecture.

Journal Article Trends 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 ... Full text Link to item Cite

A striatal interneuron circuit for continuous target pursuit.

Journal Article Nat 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 ... Full text Link to item Cite

Enhancer Histone Acetylation Modulates Transcriptional Bursting Dynamics of Neuronal Activity-Inducible Genes.

Journal Article Cell 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 ... Full text Link to item Cite

Chromatin Regulation of Neuronal Maturation and Plasticity.

Journal Article Trends 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 ... Full text Link to item Cite

Parvalbumin Interneurons of the Mouse Nucleus Accumbens are Required For Amphetamine-Induced Locomotor Sensitization and Conditioned Place Preference.

Journal Article Neuropsychopharmacology · 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 ... Full text Link to item Cite

The histone demethylase Kdm6b regulates a mature gene expression program in differentiating cerebellar granule neurons.

Journal Article Mol 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 ... Full text Link to item Cite

BayFish: Bayesian inference of transcription dynamics from population snapshots of single-molecule RNA FISH in single cells.

Journal Article Genome 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 ... Full text Link to item Cite

Transcribing the connectome: roles for transcription factors and chromatin regulators in activity-dependent synapse development.

Journal Article J 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 ... Full text Link to item Cite

Regulation and function of MeCP2 Ser421 phosphorylation in U50488-induced conditioned place aversion in mice.

Journal Article Psychopharmacology (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 ... Full text Link to item Cite

Editing the Neuronal Genome: a CRISPR View of Chromatin Regulation in Neuronal Development, Function, and Plasticity.

Journal Article Yale 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 ... Open Access Link to item Cite

The transcription factor calcium-response factor limits NMDA receptor-dependent transcription in the developing brain.

Journal Article J 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 ... Full text Link to item Cite

Genomic Views of Transcriptional Enhancers: Essential Determinants of Cellular Identity and Activity-Dependent Responses in the CNS.

Journal Article J 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 ... Full text Link to item Cite

Convergence of Parkin, PINK1, and α-Synuclein on Stress-induced Mitochondrial Morphological Remodeling.

Journal Article J 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 ... Full text Link to item Cite

Regulation of chromatin accessibility and Zic binding at enhancers in the developing cerebellum.

Journal Article Nat 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 ... Full text Link to item Cite

Core and region-enriched networks of behaviorally regulated genes and the singing genome.

Journal Article Science · 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 ... Full text Open Access Link to item Cite

The histone lysine demethylase Kdm6b is required for activity-dependent preconditioning of hippocampal neuronal survival.

Journal Article Mol 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 ... Full text Link to item Cite

Epigenetics and the regulation of stress vulnerability and resilience.

Journal Article Neuroscience · 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 ... Full text Link to item Cite

Epigenetics in brain function.

Journal Article Neuroscience · April 4, 2014 Full text Link to item Cite

MeCP2 phosphorylation limits psychostimulant-induced behavioral and neuronal plasticity.

Journal Article J 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 ... Full text Link to item Cite

BDNF mediates neuroprotection against oxygen-glucose deprivation by the cardiac glycoside oleandrin.

Journal Article J 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 ... Full text Link to item Cite

Rem2 is an activity-dependent negative regulator of dendritic complexity in vivo.

Journal Article J 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 ... Full text Link to item Cite

Neurotrophins: transcription and translation.

Journal Article Handb 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 ... Full text Link to item Cite

Acquisition of response thresholds for timed performance is regulated by a calcium-responsive transcription factor, CaRF.

Journal Article Genes 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 ... Full text Link to item Cite

Epigenetics and psychostimulant addiction.

Journal Article Cold 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 ... Full text Link to item Cite

Improved survival and reduced phenotypic severity following AAV9/MECP2 gene transfer to neonatal and juvenile male Mecp2 knockout mice.

Journal Article Mol 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 ... Full text Link to item Cite

Phosphorylation of MeCP2 at Ser421 contributes to chronic antidepressant action.

Journal Article J 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 ... Full text Link to item Cite

Members of the myocyte enhancer factor 2 transcription factor family differentially regulate Bdnf transcription in response to neuronal depolarization.

Journal Article J 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 ... Full text Link to item Cite

Mutation of MeCP2 alters transcriptional regulation of select immediate-early genes.

Journal Article Epigenetics · 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 ... Full text Link to item Cite

Regulated shuttling of the histone deacetylase HDAC5 to the nucleus may put a brake on cocaine addiction.

Journal Article Neuron · 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 ... Full text Link to item Cite

Spectral-domain differential interference contrast (SD-DIC) microscopy for measuring live cell dynamics

Journal Article Biomedical 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 ... Full text Cite

Differential regulation of MeCP2 phosphorylation in the CNS by dopamine and serotonin.

Journal Article Neuropsychopharmacology · 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 ... Full text Link to item Cite

Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function.

Journal Article Neuron · 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 ... Full text Link to item Cite

Mechanisms of specificity in neuronal activity-regulated gene transcription.

Journal Article Prog 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 ... Full text Link to item Cite

Neuronal activity-regulated gene transcription in synapse development and cognitive function.

Journal Article Cold 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 ... Full text Link to item Cite

Biological functions and transcriptional targets of CaRF in neurons.

Journal Article Cell 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 ... Full text Link to item Cite

MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants.

Journal Article Nat 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 ... Full text Link to item Cite

Reduced cortical BDNF expression and aberrant memory in Carf knock-out mice.

Journal Article J 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 ... Full text Link to item Cite

Genome-wide identification of calcium-response factor (CaRF) binding sites predicts a role in regulation of neuronal signaling pathways.

Journal Article PLoS 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 ... Full text Open Access Link to item Cite

Genome-wide identification of calcium-response factor (CaRF) binding sites predicts a role in regulation of neuronal signaling pathways

Journal Article PLoS 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 ... Full text Cite

BDNF-mediated cerebellar granule cell development is impaired in mice null for CaMKK2 or CaMKIV.

Journal Article J 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 ... Full text Link to item Cite

Biological functions of activity-dependent transcription revealed.

Journal Article Neuron · 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 ... Full text Link to item Cite

Activity-dependent regulation of brain-derived neurotrophic factor transcription

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 ... Full text Cite

Differential regulation of c-jun and CREB by acrolein and 4-hydroxynonenal.

Journal Article Free 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 ... Full text Link to item Cite

Transcriptional control of cognitive development.

Journal Article Curr 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 ... Full text Link to item Cite

Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2.

Journal Article Science · 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 ... Full text Link to item Cite

Upstream stimulatory factors are mediators of Ca2+-responsive transcription in neurons.

Journal Article J 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 ... Full text Link to item Cite

A calcium-responsive transcription factor, CaRF, that regulates neuronal activity-dependent expression of BDNF.

Journal Article Neuron · 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 ... Full text Link to item Cite

Development: Fattening up the synapse

Journal Article Nature Reviews Neuroscience · January 1, 2002 Full text Cite

Calcium regulation of neuronal gene expression.

Journal Article Proc 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 ... Full text Link to item Cite

Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer.

Journal Article Nat 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 ... Full text Link to item Cite

Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms.

Journal Article Science · 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 ... Full text Link to item Cite

Protein targeting in neurons and endocrine cells.

Journal Article Advances in pharmacology (San Diego, Calif.) · 1998 Cite

Targeting of the synaptic vesicle protein synaptobrevin in the axon of cultured hippocampal neurons: evidence for two distinct sorting steps.

Journal Article J 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 ... Full text Link to item Cite

Identification of a somatodendritic targeting signal in the cytoplasmic domain of the transferrin receptor.

Journal Article J 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 ... Full text Link to item Cite