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Volume 503 Issue 7474, 7 November 2013

Mutations in SHANK3, the gene encoding the SHANK3 synaptic scaffolding protein, are associated with autism, intellectual disability and schizophrenia, but the effect of SHANK3 overexpression is much less clear. Huda Zoghbi and colleagues now show that mice overexpressing Shank3 exhibit mania-like behaviour, seizures and alterations in excitatory/inhibitory balance of neuronal activity. Consistent with the findings in mouse, they identify two patients with hyperkinetic disorders carrying a genetic duplication of the SHANK3-containing region on chromosome 22. These findings support the hypothesis that incorrect gene dosage in either direction (both over- and under-expression) may be detrimental. The authors suggest that the mice used in this work provide a model for the pharmacogenetic underpinnings of some forms of bipolar disorder. Cover: Wei-Hisang Huang.


  • Editorial |

    Europe’s mega-project to simulate the human brain has much to offer neuroscience research — whether or not it delivers on its central promise.

  • Editorial |

    Governments need to strengthen support for scientists who preserve our cultural heritage.

  • Editorial |

    The behaviour of millions of minuscule beads reveals some secrets of collective motion.

World View

Research Highlights

Seven Days

  • Seven Days |

    The week in science: India launches its first spacecraft to Mars, a new dolphin species is reported, and a rare hybrid eclipse wows sky-watchers.



News Feature

  • News Feature |

    Barack Obama announced his BRAIN Initiative on 2 April. Ever since, neuroscientists have been scrambling to work out what it actually is.

    • Helen Shen


Books & Arts

  • Books & Arts |

    Tim Radford contemplates three fascinating studies on what it means to be human.

    • Tim Radford
  • Books & Arts |

    Jad Abumrad co-hosts Radiolab, the science-heavy, nationally syndicated US public-radio show. As it enters its tenth year, he takes time out from a 21-city North American tour with co-host Robert Krulwich to talk about crafting high-speed science stories on radio.

    • Jascha Hoffman



News & Views

  • News & Views |

    It emerges that a transcription program differentially regulates inhibitory inputs in distinct neuronal compartments — an unexpected coordinated switch for achieving experience-dependent 'plasticity' in neural circuits. See Letter p.121

    • Emily Sylwestrak
    • Peter Scheiffele
  • News & Views |

    Populations of rolling particles have been shown to display unidirectional collective motion in a racetrack enclosure. Theoretical modelling suggests that hydrodynamic and electrostatic effects promote such behaviour. See Letter p.95

    • Michael Shelley
  • News & Views |

    Research on guppies provides the most definitive evidence yet for the rare-male effect — a long-standing hypothesis to explain the perplexing maintenance of variation in traits that are subject to strong mate choice. See Letter p.108

    • Jeffrey S. McKinnon
    • Maria R. Servedio
  • News & Views |

    Decisions can differ depending on the context that surrounds them. Analyses of the prefrontal cortex region of the monkey brain indicate that a dynamical process at the neuronal population level controls this behaviour. See Article p.78

    • Jeffrey C. Erlich
    • Carlos D. Brody
  • News & Views |

    Uncertainty in estimates of the effects of aerosols on climate stems from poor knowledge of the past, pristine atmosphere — so getting a better understanding of these effects might not be as useful as was thought. See Article p.67

    • Bjorn Stevens
  • News & Views |

    In response to bad news about risk, young adolescents alter estimates of their own vulnerability to adverse events less accurately than older people. The finding has implications for managing risk-taking behaviour in young people.

    • Valerie F. Reyna

Review Article

  • Review Article |

    The connectivity of cortical neurons relates to the way in which they encode sensory features, and integrate them with behavioural context; these factors are discussed in relation to recent research, the major questions still to be addressed, and emerging techniques that may help to answer these.

    • Kenneth D. Harris
    • Thomas D. Mrsic-Flogel
  • Review Article |

    An alternative view of diabetes is presented in which blood glucose homeostasis is achieved via collective actions of two regulatory systems: a brain-centred glucoregulatory system (BCGS), which works together with the pancreatic islets; defects in both systems may be required for diabetes to occur, and interventions targeting both systems may have greater therapeutic potential.

    • Michael W. Schwartz
    • Randy J. Seeley
    • David D’Alessio


  • Article |

    It has been assumed that a better understanding of the effects of anthropogenic aerosols will greatly reduce the large uncertainties associated with our predictions of the radiative forcing effects of aerosols on climate; however, this study shows that nearly half of the uncertainty in the radiative effect of aerosols on clouds derives from uncertainties in pre-industrial natural aerosols.

    • K. S. Carslaw
    • L. A. Lee
    • J. R. Pierce
  • Article |

    Mouse and human studies reveal that incorrect gene dosage of SHANK3 (a gene linked to some human neuropsychiatric disorders, including autism spectrum disorder) is associated with behavioural abnormalities including mania, possibly because of actin regulation problems in excitatory/inhibitory synapses.

    • Kihoon Han
    • J. Lloyd Holder Jr
    • Huda Y. Zoghbi
  • Article |

    This study shows that in monkeys making context-dependent decisions, task-relevant and task-irrelevant signals are confusingly intermixed in single units of the prefrontal cortex, but are readily understood in the framework of a dynamical process unfolding at the level of the population; a recurrently connected neural network model reproduces key features of the data and suggests a novel mechanism for selection and integration of task-relevant evidence towards a decision.

    • Valerio Mante
    • David Sussillo
    • William T. Newsome


  • Letter |

    Populations of millions of colloidal rolling particles are shown to self-organize to achieve coherent motion; comparison between experiment and theory based on the microscopic interactions between these ‘rollers’ suggests that hydrodynamic interactions promote the emergence of the collective motion.

    • Antoine Bricard
    • Jean-Baptiste Caussin
    • Denis Bartolo
  • Letter |

    Magnetic fields micropatterned within a paramagnetic fluid can simultaneously trap and position both magnetic and non-magnetic microparticles, the latter including live bacteria.

    • Ahmet F. Demirörs
    • Pramod P. Pillai
    • Bartosz A. Grzybowski
  • Letter |

    The structure of molten basalt up to 60 GPa by means of in situ X-ray diffraction is described, with the coordination of silicon increasing from four under ambient conditions to six at 35 GPa, and subsequent reduced melt compressibility, which seems to affect siderophile-element partitioning.

    • Chrystèle Sanloup
    • James W. E. Drewitt
    • Wolfgang Morgenroth
  • Letter |

    Manipulation of the frequency of naturally occurring colour patterns within replicate pools of fish at three sites shows that males with rare colour patterns have higher reproductive fitness, demonstrating negative frequency-dependent selection mediated by sexual selection.

    • Kimberly A. Hughes
    • Anne E. Houde
    • F. Helen Rodd
  • Letter |

    Neuronal dendrites are not passive cables, but whether their excitability contributes to computation at the cell’s soma has been uncertain; by observing and interfering with dendritic ‘spikes’ during sensory stimulation, it is now shown that active dendritic processing enhances somatic orientation selectivity, a fundamental brain computation.

    • Spencer L. Smith
    • Ikuko T. Smith
    • Michael Häusser
  • Letter |

    Failure of integrin-mediated cell-matrix attachment is sufficient to initiate dermal fibrosis and autoimmunity in mouse models of scleroderma; integrin-modulating therapies prevent the recruitment and activation of plasmacytoid dendritic cells that appear central to immunological dysregulation and maintenance of the pro-fibrotic synthetic programme.

    • Elizabeth E. Gerber
    • Elena M. Gallo
    • Harry C. Dietz
  • Letter |

    The direction of integrin signalling is found to be determined by the coordinated and opposing binding waves of talin and Gα13 to the same region of the integrin β3 cytoplasmic domain at mutually exclusive but distinct sites, and a potent new anti-thrombotic drug that does not cause bleeding is designed on the basis of these findings.

    • Bo Shen
    • Xiaojuan Zhao
    • Xiaoping Du
  • Letter |

    This study finds a direct correlation between LARGE-glycan extension on dystroglycan and the protein’s capacity for extracellular matrix ligands; in regenerating mouse muscle, short LARGE-glycan polysaccharides cause various defects, including muscle dysfunction and a predisposition to dystrophy, and in muscular dystrophy patients, increased clinical severity of disease corresponds to shorter LARGE-glycans.

    • Matthew M. Goddeeris
    • Biming Wu
    • Kevin P. Campbell
  • Letter |

    LeuT, a bacterial homologue of eukaryotic biogenic amine transporters (BATs), is engineered to harbour human BAT-like pharmacology by the mutation of key residues around the primary binding pocket; this mutant is able to bind several classes of antidepressant drug with high affinity, helping to define their common mechanisms of action.

    • Hui Wang
    • April Goehring
    • Eric Gouaux



Technology Feature

  • Technology Feature |

    Tools that make it possible to chart every neuron and its connections are helping neuroscientists to realize their dream of whole-brain maps.

    • Vivien Marx



  • Column |

    A love affair with research can be just as heartbreaking as romantic love, says Christopher Schmitt.

    • Christopher Schmitt


  • Futures |

    Off the scale.

    • H.E. Roulo
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