Nature Neuroscience Contents: May 2015 Volume 18 Number 5, pp 611 - 786

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Advertisement CALL FOR PAPERS: Bioelectronic Medicine is an open access, biomedical journal published by the Feinstein Institute Press. Bioelectronic medicine combines molecular medicine, bioengineering, and neuroscience to discover and develop nerve stimulating and sensing technologies to regulate biological processes and treat disease. www.bioelecmed.org.     TABLE OF CONTENTS May 2015 Volume 18, Issue 5 News and Views Review Brief Communication Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   News and Views Top Exome sequencing uncovers hidden pathways in familial and sporadic ALS   pp611 - 613 Conceicao Bettencourt and Henry Houlden doi:10.1038/nn.4012 Amyotrophic lateral sclerosis (ALS) is a complex and as yet untreatable neurodegenerative disorder. We discuss two examples of exome sequencing in large international collections of familial and sporadic ALS cases that are revealing new and potentially treatable pathways, such as those involving autophagy and neuroinflammation. See also: Article by Freischmidt et al. Stem cells: slow and steady wins the race   pp613 - 614 Wieland B Huttner doi:10.1038/nn.4009 How are quiescent adult neural stem cells (NSCs) generated during development? A study now identifies a reserve population of p57-expressing, slowly dividing embryonic neural progenitors that later give rise to adult NSCs. See also: Article by Furutachi et al. Strength in more than numbers   pp614 - 616 Nathaniel B Sawtell and L F Abbott doi:10.1038/nn.4006 Theory suggests that cerebellar granule cells combine sensory and motor signals originating from different sources. An unexpected logic governing how granule cells process different input sources may enhance computational power. See also: Article by Chabrol et al. Divide and conquer: strategic decision areas   pp616 - 618 Nils Kolling and Laurence T Hunt doi:10.1038/nn.4005 Strategic decisions can prove difficult to study. The board game shogi is used to investigate the functional neuroanatomy of strategic decisions, revealing different brain areas from those engaged by other forms of choice. See also: Article by Wan et al. Good vibrations with deep brain stimulation   pp618 - 619 Ziv M Williams doi:10.1038/nn.4007 Insight into the mechanism by which deep brain stimulation exerts its therapeutic effects comes from recording in motor cortical regions of neurosurgical subjects undergoing subthalamic nucleus deep brain stimulation. See also: Article by de Hemptinne et al. The cost of brain structure   p619 Jean Mary Zarate doi:10.1038/nn0515-619 See also: Article by Noble et al. Neuroscience JOBS of the week Postdoctoral Researcher Neurobiology / Neuroscience University of Kansas Postdoctoral Position in Systems Neuroscience University of Rochester Research Fellow in Animal Behavior Imaging Institute for Molecular and Cell Biology Postdoctoral researcher Uppsala University Postdoctoral Scholar Laureate Institute for Brain Research More Science jobs from Neuroscience EVENT Champalimaud Neuroscience Symposium � Perspectives on Social Behaviour 16.09.15 Lisbon, Portugal More science events from Review Top What the orbitofrontal cortex does not do   pp620 - 627 Thomas A Stalnaker, Nisha K Cooch and Geoffrey Schoenbaum doi:10.1038/nn.3982 In the last 25 years, explosive interest has implicated the orbitofrontal cortex in nearly every function known to cognitive neuroscience. Yet scientific progress comes as much from questioning existing ideas as proposing new ones. This review discusses major theories of orbitofrontal function and the data that invalidate these ideas. Brief Communication Top Synaptic vesicle release regulates myelin sheath number of individual oligodendrocytes in vivo   pp628 - 630 Sigrid Mensch, Marion Baraban, Rafael Almeida, Tim Czopka, Jessica Ausborn et al. doi:10.1038/nn.3991 Mensch et al. investigate how neuronal activity regulates CNS myelination in vivo, using zebrafish as a model. They find that blocking synaptic vesicle release reduces, and that stimulating neuronal activity increases, the number of myelin sheath made by the myelinating glia of the CNS (oligodendrocytes). These data show that neuronal activity regulates the myelinating capacity of individual oligodendrocytes. Articles Top Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia   pp631 - 636 Axel Freischmidt, Thomas Wieland, Benjamin Richter, Wolfgang Ruf, Veronique Schaeffer et al. doi:10.1038/nn.4000 The authors show that haploinsufficiency of TBK1 causes familial forms of the neurodegenerative diseases ALS and FTD. Loss of binding of a TBK1 protein interaction domain to optineurin, a protein previously linked to ALS, is sufficient to cause the disease. Both proteins regulate autophagy and inflammation. Single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex   pp637 - 646 Matthew B Johnson, Peter P Wang, Kutay D Atabay, Elisabeth A Murphy, Ryan N Doan et al. doi:10.1038/nn.3980 The developing human cortex contains diverse populations of neural progenitor cells, including a large proportion of outer radial glia (ORG), a progenitor type that is rare in the mouse. The authors identify a transcriptional signature of ORG characterized by markers of neuronal lineage fate and use single-cell analyses to contrast the heterogeneity of cortical progenitors across human, mouse and ferret. Regulation of chromatin accessibility and Zic binding at enhancers in the developing cerebellum   pp647 - 656 Christopher L Frank, Fang Liu, Ranjula Wijayatunge, Lingyun Song, Matthew T Biegler et al. doi:10.1038/nn.3995 The authors use developmental changes in chromatin accessibility to identify thousands of enhancer elements that are active at different postnatal developmental stages in granule neurons of the cerebellum. Zic transcription factors were found to promote gene expression patterns key for neuronal maturation by binding to late-acting enhancer elements. Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells   pp657 - 665 Shohei Furutachi, Hiroaki Miya, Tomoyuki Watanabe, Hiroki Kawai, Norihiko Yamasaki et al. doi:10.1038/nn.3989 Furutachi et al. identified a slowly dividing subpopulation of embryonic progenitors that later gives rise to most adult neural stem cells (NSCs) in the subependymal zone. Moreover, they found that p57 is responsible for the slow cell cycle of this embryonic population and acts causally in the emergence of adult NSCs. A coding-independent function of an alternative Ube3a transcript during neuronal development   pp666 - 673 Jeremy Valluy, Silvia Bicker, Ayla Aksoy-Aksel, Martin Lackinger, Simon Sumer et al. doi:10.1038/nn.3996 This work shows a nocoding function of Ube3a1 RNA, an alternative transcript encoded by the Angelman syndrome gene Ube3a. Valluy et al. observe that Ube3a1 RNA competes with dendritic mRNAs for microRNAs, thereby regulating dendrite arborization and spine maturation of hippocampal neurons. These findings suggest a function for competing endogenous RNAs in synaptic development. GABAergic regulation of cerebellar NG2 cell development is altered in perinatal white matter injury   pp674 - 682 Marzieh Zonouzi, Joseph Scafidi, Peijun Li, Brian McEllin, Jorge Edwards et al. doi:10.1038/nn.3990 The authors show that chronic neonatal hypoxia reduces GABAA receptor-mediated signaling to oligodendrocyte precursor cells in the cerebellar white matter and enhances their proliferation, delays oligodendrocyte maturation and disrupts myelination. Following hypoxia, treatment with a GABA uptake blocker restores myelination. Neuronal activity biases axon selection for myelination in vivo   pp683 - 689 Jacob H Hines, Andrew M Ravanelli, Rani Schwindt, Ethan K Scott and Bruce Appel doi:10.1038/nn.3992 Using zebrafish, the authors show that neuronal activity influences which axons are selected for myelination by promoting the growth and stability of oligodendrocyte sheaths on axons. Myelination of axons in response to activity could modulate the conduction properties of specific neural circuits, thereby contributing to brain plasticity. Brain feminization requires active repression of masculinization via DNA methylation   pp690 - 697 Bridget M Nugent, Christopher L Wright, Amol C Shetty, Georgia E Hodes, Kathryn M Lenz et al. doi:10.1038/nn.3988 Hormone-induced brain masculinization occurs during a perinatal sensitive period but endures into adulthood. Researchers explored DNA methylation as a candidate mechanism. Methylation is higher in female brain and suppresses masculinization genes, which are liberated by hormone-induced reductions in DNMT activity in males. Pharmacological inhibition of DNMTs reduces methylation, masculinizes female brain and behavior and reopens the sensitive period. Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity   pp698 - 707 Daisuke Tsuboi, Keisuke Kuroda, Motoki Tanaka, Takashi Namba, Yukihiko Iizuka et al. doi:10.1038/nn.3984 DISC1 is believed to be a genetic risk factor for schizophrenia, but its pathophysiological functions are not fully understood. Using proteomics, Tsuboi et al. identify several RNA-binding proteins, including HZF, as DISC1 interactors and reveal that DISC1, together with HZF, regulates the dendritic transport of ITPR1 mRNA to modulate synaptic plasticity. Ca2+ signaling in astrocytes from Ip3r2–/– mice in brain slices and during startle responses in vivo   pp708 - 717 Rahul Srinivasan, Ben S Huang, Sharmila Venugopal, April D Johnston, Hua Chai et al. doi:10.1038/nn.4001 In this manuscript, the authors use state-of-the-art imaging methods to report the discovery of novel forms of astrocyte calcium signaling in wild-type mice and in mutant mice previously thought to lack astrocyte calcium dynamics. The findings have important implications for experimental and theoretical studies of astrocyte functions in neural circuits. Synaptic diversity enables temporal coding of coincident multisensory inputs in single neurons   pp718 - 727 Francois P Chabrol, Alexander Arenz, Martin T Wiechert, Troy W Margrie and David A DiGregorio doi:10.1038/nn.3974 Processing multiple sensory modalities is critical for executing complex behaviors. This study finds that single cerebellar granule cells integrate inputs from both vestibular and visual input pathways, each exhibiting characteristic synaptic strengths and plasticities. These are translated into output dynamics that enhance the network's representation of complex sensory contexts. Mesopontine median raphe regulates hippocampal ripple oscillation and memory consolidation   pp728 - 735 Dong V Wang, Hau-Jie Yau, Carl J Broker, Jen-Hui Tsou, Antonello Bonci et al. doi:10.1038/nn.3998 It has been suggested that hippocampal sharp-wave ripples (SWR) are important for memory consolidation. Here, the authors found that the activation of a non-serotoninergic subpopulation of median raphe neurons suppresses hippocampal sharp-wave ripples and impairs memory consolidation. These findings uncover a new brainstem influence on SWR and hippocampal memory function. Global network influences on local functional connectivity   pp736 - 743 Adam C Snyder, Michael J Morais, Cory M Willis and Matthew A Smith doi:10.1038/nn.3979 The relationship between EEG oscillations and underlying neural activity is unclear. The authors find a U-shaped relationship between the two in visual cortex that is linked to visuospatial attention performance in monkeys. A neural network model indicates a critical role for selective inputs to inhibitory neurons. Learning-induced autonomy of sensorimotor systems   pp744 - 751 Danielle S Bassett, Muzhi Yang, Nicholas F Wymbs and Scott T Grafton doi:10.1038/nn.3993 The authors used new network-analysis algorithms to examine how distributed networks of brain areas are reorganized as humans learn a new motor skill. Using fMRI, the authors found that learning induced autonomy of sensorimotor systems and that a release of cognitive control hubs predicted individual differences in learning. Neural encoding of opposing strategy values in anterior and posterior cingulate cortex   pp752 - 759 Xiaohong Wan, Kang Cheng and Keiji Tanaka doi:10.1038/nn.3999 In complex environments, we first select heuristic strategies and next determine concrete responses. BOLD imaging while subjects encountered game situations (shogi) revealed that activity in rostral anterior cingulate cortex and posterior cingulate cortex is correlated with defense and attack values, respectively. The cingulate cortex plays essential roles in strategy decision. Medial prefrontal cortical activity reflects dynamic re-evaluation during voluntary persistence   pp760 - 766 Joseph T McGuire and Joseph W Kable doi:10.1038/nn.3994 Prolonged persistence toward delayed rewards is beneficial in some environments but counterproductive in others. Human decision makers calibrate persistence according to the statistics of their environment, and delay-period activity in ventromedial prefrontal cortex reflects a dynamic, context-sensitive valuation signal that could underlie adaptive decisions between persisting and quitting. Model-based choices involve prospective neural activity   pp767 - 772 Bradley B Doll, Katherine D Duncan, Dylan A Simon, Daphna Shohamy and Nathaniel D Daw doi:10.1038/nn.3981 Although it has been widely hypothesized that decisions can be guided by mental simulation of their likely consequences, there has not been direct evidence linking prospection to choices. Here, using fMRI, the authors show that neural representation of future outcomes is related to the choices that participants make. Family income, parental education and brain structure in children and adolescents   pp773 - 778 Kimberly G Noble, Suzanne M Houston, Natalie H Brito, Hauke Bartsch, Eric Kan et al. doi:10.1038/nn.3983 Socioeconomic status is associated with cognitive development, but the extent to which this reflects neuroanatomical differences is unclear. In 1,099 children and adolescents, family income was nonlinearly associated with brain surface area, and this association was greatest among disadvantaged children. Further, surface area mediated links between income and executive functioning. See also: News and Views by Zarate Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease   pp779 - 786 Coralie de Hemptinne, Nicole C Swann, Jill L Ostrem, Elena S Ryapolova-Webb, Marta San Luciano et al. doi:10.1038/nn.3997 By examining Parkinson's disease patients undergoing deep brain stimulation (DBS) implantation surgery, this study shows that therapeutic DBS acts on the primary motor cortex to reversibly reduce excessive coupling between the phase of the beta rhythm and the amplitude of broadband activity over a similar time course as the reduction in parkinsonian motor signs. Top Advertisement Epigenome Roadmap Nature Publishing Group presents an online portal - the Epigenome Roadmap - which collects key research papers from The NIH Roadmap Epigenomics Program, complemented by thematical 'threads' to help the readers mine the wealth of available information. 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