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Neuron

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https://www.readbyqxmd.com/read/28065649/translation-of-expanded-cgg-repeats-into-fmrpolyg-is-pathogenic-and-may-contribute-to-fragile-x-tremor-ataxia-syndrome
#1
Chantal Sellier, Ronald A M Buijsen, Fang He, Sam Natla, Laura Jung, Philippe Tropel, Angeline Gaucherot, Hugues Jacobs, Hamid Meziane, Alexandre Vincent, Marie-France Champy, Tania Sorg, Guillaume Pavlovic, Marie Wattenhofer-Donze, Marie-Christine Birling, Mustapha Oulad-Abdelghani, Pascal Eberling, Frank Ruffenach, Mathilde Joint, Mathieu Anheim, Veronica Martinez-Cerdeno, Flora Tassone, Rob Willemsen, Renate K Hukema, Stéphane Viville, Cecile Martinat, Peter K Todd, Nicolas Charlet-Berguerand
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a limited expansion of CGG repeats in the 5' UTR of FMR1. Two mechanisms are proposed to cause FXTAS: RNA gain-of-function, where CGG RNA sequesters specific proteins, and translation of CGG repeats into a polyglycine-containing protein, FMRpolyG. Here we developed transgenic mice expressing CGG repeat RNA with or without FMRpolyG. Expression of FMRpolyG is pathogenic, while the sole expression of CGG RNA is not...
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28065650/network-dynamics-mediate-circadian-clock-plasticity
#2
Abdelhalim Azzi, Jennifer A Evans, Tanya Leise, Jihwan Myung, Toru Takumi, Alec J Davidson, Steven A Brown
A circadian clock governs most aspects of mammalian behavior. Although its properties are in part genetically determined, altered light-dark environment can change circadian period length through a mechanism requiring de novo DNA methylation. We show here that this mechanism is mediated not via cell-autonomous clock properties, but rather through altered networking within the suprachiasmatic nuclei (SCN), the circadian "master clock," which is DNA methylated in region-specific manner. DNA methylation is necessary to temporally reorganize circadian phasing among SCN neurons, which in turn changes the period length of the network as a whole...
January 2, 2017: Neuron
https://www.readbyqxmd.com/read/28065648/taok2-kinase-mediates-psd95-stability-and-dendritic-spine-maturation-through-septin7-phosphorylation
#3
Smita Yadav, Juan A Oses-Prieto, Christian J Peters, Jing Zhou, Samuel J Pleasure, Alma L Burlingame, Lily Y Jan, Yuh-Nung Jan
Abnormalities in dendritic spines are manifestations of several neurodevelopmental and psychiatric diseases. TAOK2 is one of the genes in the 16p11.2 locus, copy number variations of which are associated with autism and schizophrenia. Here, we show that the kinase activity of the serine/threonine kinase encoded by TAOK2 is required for spine maturation. TAOK2 depletion results in unstable dendritic protrusions, mislocalized shaft-synapses, and loss of compartmentalization of NMDA receptor-mediated calcium influx...
December 29, 2016: Neuron
https://www.readbyqxmd.com/read/28041880/dynamic-cell-type-specific-roles-for-gabaergic-interneurons-in-a-mouse-model-of-optogenetically-inducible-seizures
#4
Sattar Khoshkhoo, Daniel Vogt, Vikaas S Sohal
GABAergic interneurons play critical roles in seizures, but it remains unknown whether these vary across interneuron subtypes or evolve during a seizure. This uncertainty stems from the unpredictable timing of seizures in most models, which limits neuronal imaging or manipulations around the seizure onset. Here, we describe a mouse model for optogenetic seizure induction. Combining this with calcium imaging, we find that seizure onset rapidly recruits parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptitde (VIP)-expressing interneurons, whereas excitatory neurons are recruited several seconds later...
December 29, 2016: Neuron
https://www.readbyqxmd.com/read/28041882/lncrna-functional-networks-in-oligodendrocytes-reveal-stage-specific-myelination-control-by-an-lncol1-suz12-complex-in-the-cns
#5
Danyang He, Jincheng Wang, Yulan Lu, Yaqi Deng, Chuntao Zhao, Lingli Xu, Yinhuai Chen, Yueh-Chiang Hu, Wenhao Zhou, Q Richard Lu
Long noncoding RNAs (lncRNAs) are emerging as important regulators of cellular functions, but their roles in oligodendrocyte myelination remain undefined. Through de novo transcriptome reconstruction, we establish dynamic expression profiles of lncRNAs at different stages of oligodendrocyte development and uncover a cohort of stage-specific oligodendrocyte-restricted lncRNAs, including a conserved chromatin-associated lncOL1. Co-expression network analyses further define the association of distinct oligodendrocyte-expressing lncRNA clusters with protein-coding genes and predict lncRNA functions in oligodendrocyte myelination...
December 28, 2016: Neuron
https://www.readbyqxmd.com/read/28041883/phase-locked-inhibition-but-not-excitation-underlies-hippocampal-ripple-oscillations-in-awake-mice-in%C3%A2-vivo
#6
Jian Gan, Shih-Ming Weng, Alejandro J Pernía-Andrade, Jozsef Csicsvari, Peter Jonas
Sharp wave-ripple (SWR) oscillations play a key role in memory consolidation during non-rapid eye movement sleep, immobility, and consummatory behavior. However, whether temporally modulated synaptic excitation or inhibition underlies the ripples is controversial. To address this question, we performed simultaneous recordings of excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) and local field potentials (LFPs) in the CA1 region of awake mice in vivo. During SWRs, inhibition dominated over excitation, with a peak conductance ratio of 4...
December 22, 2016: Neuron
https://www.readbyqxmd.com/read/28041884/synaptic-correlates-of-working-memory-capacity
#7
Yuanyuan Mi, Mikhail Katkov, Misha Tsodyks
Psychological studies indicate that human ability to keep information in readily accessible working memory is limited to four items for most people. This extremely low capacity severely limits execution of many cognitive tasks, but its neuronal underpinnings remain unclear. Here we show that in the framework of synaptic theory of working memory, capacity can be analytically estimated to scale with characteristic time of short-term synaptic depression relative to synaptic current time constant. The number of items in working memory can be regulated by external excitation, enabling the system to be tuned to the desired load and to clear the working memory of currently held items to make room for new ones...
December 21, 2016: Neuron
https://www.readbyqxmd.com/read/28041881/nipbl-interacts-with-zfp609-and-the-integrator-complex-to-regulate-cortical-neuron-migration
#8
Debbie L C van den Berg, Roberta Azzarelli, Koji Oishi, Ben Martynoga, Noelia Urbán, Dick H W Dekkers, Jeroen A Demmers, François Guillemot
Mutations in NIPBL are the most frequent cause of Cornelia de Lange syndrome (CdLS), a developmental disorder encompassing several neurological defects, including intellectual disability and seizures. How NIPBL mutations affect brain development is not understood. Here we identify Nipbl as a functional interaction partner of the neural transcription factor Zfp609 in brain development. Depletion of Zfp609 or Nipbl from cortical neural progenitors in vivo is detrimental to neuronal migration. Zfp609 and Nipbl overlap at genomic binding sites independently of cohesin and regulate genes that control cortical neuron migration...
December 20, 2016: Neuron
https://www.readbyqxmd.com/read/28056347/paying-attention-to-the-cortical-layers
#9
Matthew W Self, Pieter R Roelfsema
In this issue of Neuron, Nandy et al. (2017) reveal a number of important new insights into the neural mechanisms that are responsible for attentional selection.
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28056346/diversification-of-c-%C3%A2-elegans-motor-neuron-identity-via-selective-effector-gene-repression
#10
Sze Yen Kerk, Paschalis Kratsios, Michael Hart, Romulo Mourao, Oliver Hobert
A common organizational feature of nervous systems is the existence of groups of neurons that share common traits but can be divided into individual subtypes based on anatomical or molecular features. We elucidate the mechanistic basis of neuronal diversification processes in the context of C.elegans ventral cord motor neurons that share common traits that are directly activated by the terminal selector UNC-3. Diversification of motor neurons into different classes, each characterized by unique patterns of effector gene expression, is controlled by distinct combinations of phylogenetically conserved, class-specific transcriptional repressors...
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28056345/extracellular-remodeling-by-lysosomes-an-inside-out-mechanism-of-spine-plasticity
#11
Paul R Evans, Ryohei Yasuda
In this issue of Neuron, Padamsey et al. (2017) demonstrate that neuronal activity triggers lysosomal fusion with the plasma membrane in dendrites. Quite unexpectedly, the lysosomes release signaling molecules that induce extracellular matrix remodeling to support long-lasting dendritic spine plasticity.
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28056344/raise-the-roof-boosting-the-efficacy-of-a-spinal-muscular-atrophy-therapy
#12
Nicholas J Kramer, Aaron D Gitler
Spinal muscular atrophy is the most common genetic killer of infants. A therapy shows promise in the clinic, but there is a potential limit to its efficacy. In this issue of Neuron, d'Ydewalle et al. (2017) devise a new way to make it more effective.
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28056343/perceptual-decision-making-in-rodents-monkeys-and-humans
#13
REVIEW
Timothy D Hanks, Christopher Summerfield
Perceptual decision making is the process by which animals detect, discriminate, and categorize information from the senses. Over the past two decades, understanding how perceptual decisions are made has become a central theme in the neurosciences. Exceptional progress has been made by recording from single neurons in the cortex of the macaque monkey and using computational models from mathematical psychology to relate these neural data to behavior. More recently, however, the range of available techniques and paradigms has dramatically broadened, and researchers have begun to harness new approaches to explore how rodents and humans make perceptual decisions...
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28056342/pathway-and-cell-specific-kappa-opioid-receptor-modulation-of-excitation-inhibition-balance-differentially%C3%A2-gates-d1-and-d2-accumbens-neuron-activity
#14
Hugo A Tejeda, Jocelyn Wu, Alana R Kornspun, Marco Pignatelli, Vadim Kashtelyan, Michael J Krashes, Brad B Lowell, William A Carlezon, Antonello Bonci
Endogenous dynorphin signaling via the kappa-opioid receptor (KOR) in the nucleus accumbens (NAcc) powerfully mediates negative affective states and stress reactivity. Excitatory inputs from the hippocampus and amygdala play a fundamental role in shaping the activity of both NAcc D1 and D2 MSNs, which encode positive and negative motivational valences, respectively. However, a circuit-based mechanism by which KOR modulation of excitation-inhibition balance modifies D1 and D2 MSN activity is lacking. Here, we provide a comprehensive synaptic framework wherein presynaptic KOR inhibition decreases the excitatory drive of D1 MSN activity by the amygdala, but not the hippocampus...
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28056341/bringing-kids-into-the-scientific-review-process
#15
Sabine Kastner, Robert T Knight
Frontiers for Young Minds puts kids in charge of scientific publications by having them control the review process. This provides kids the ability to shape the way science is taught and to better understand the scientific method.
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28056340/great-expectations-anticipatory-control-of-magnocellular-vasopressin-neurons
#16
Alan G Watts
Real-time activity measurements of genetically identified neuroendocrine vasopressin neurons show they can anticipate osmotic challenges. In this issue of Neuron, Mandelblat-Cerf et al. (2017) show that correlating these results with ongoing behavior and plasma osmolality points to the existence of brain networks that integrate exterosensory cues with interosensory signals to drive neuroendocrine output.
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28017473/huntingtin-mediated-multipolar-bipolar-transition-of-newborn-cortical-neurons-is-critical-for-their-postnatal-neuronal-morphology
#17
Monia Barnat, Julien Le Friec, Caroline Benstaali, Sandrine Humbert
In the developing cortex, projection neurons undergo multipolar-bipolar transition, radial-directed migration, and maturation. The contribution of these developmental steps to the structure of the adult cortex is not completely understood. Here, we report that huntingtin (HTT), the protein mutated in Huntington's disease, is enriched in polarizing projection neurons. The depletion of HTT in postmitotic projection neurons leads to the mislocalization of layer-specific neuronal populations in the mouse neocortex...
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28017472/loss-of-nardilysin-a-mitochondrial-co-chaperone-for-%C3%AE-ketoglutarate-dehydrogenase-promotes-mtorc1-activation-and-neurodegeneration
#18
Wan Hee Yoon, Hector Sandoval, Sonal Nagarkar-Jaiswal, Manish Jaiswal, Shinya Yamamoto, Nele A Haelterman, Nagireddy Putluri, Vasanta Putluri, Arun Sreekumar, Tulay Tos, Ayse Aksoy, Taraka Donti, Brett H Graham, Mikiko Ohno, Eiichiro Nishi, Jill Hunter, Donna M Muzny, Jason Carmichael, Joseph Shen, Valerie A Arboleda, Stanley F Nelson, Michael F Wangler, Ender Karaca, James R Lupski, Hugo J Bellen
We previously identified mutations in Nardilysin (dNrd1) in a forward genetic screen designed to isolate genes whose loss causes neurodegeneration in Drosophila photoreceptor neurons. Here we show that NRD1 is localized to mitochondria, where it recruits mitochondrial chaperones and assists in the folding of α-ketoglutarate dehydrogenase (OGDH), a rate-limiting enzyme in the Krebs cycle. Loss of Nrd1 or Ogdh leads to an increase in α-ketoglutarate, a substrate for OGDH, which in turn leads to mTORC1 activation and a subsequent reduction in autophagy...
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28017471/the-antisense-transcript-smn-as1-regulates-smn-expression-and-is-a-novel-therapeutic-target-for-spinal-muscular-atrophy
#19
Constantin d'Ydewalle, Daniel M Ramos, Noah J Pyles, Shi-Yan Ng, Mariusz Gorz, Celeste M Pilato, Karen Ling, Lingling Kong, Amanda J Ward, Lee L Rubin, Frank Rigo, C Frank Bennett, Charlotte J Sumner
The neuromuscular disorder spinal muscular atrophy (SMA), the most common inherited killer of infants, is caused by insufficient expression of survival motor neuron (SMN) protein. SMA therapeutics development efforts have focused on identifying strategies to increase SMN expression. We identified a long non-coding RNA (lncRNA) that arises from the antisense strand of SMN, SMN-AS1, which is enriched in neurons and transcriptionally represses SMN expression by recruiting the epigenetic Polycomb repressive complex-2...
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28017470/a-central-amygdala-crf-circuit-facilitates-learning-about-weak-threats
#20
Christina A Sanford, Marta E Soden, Madison A Baird, Samara M Miller, Jay Schulkin, Richard D Palmiter, Michael Clark, Larry S Zweifel
Fear is a graded central motive state ranging from mild to intense. As threat intensity increases, fear transitions from discriminative to generalized. The circuit mechanisms that process threats of different intensity are not well resolved. Here, we isolate a unique population of locally projecting neurons in the central nucleus of the amygdala (CeA) that produce the neuropeptide corticotropin-releasing factor (CRF). CRF-producing neurons and CRF in the CeA are required for discriminative fear, but both are dispensable for generalized fear at high US intensities...
January 4, 2017: Neuron
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