Volume 22 Issue 2, February 2019

Volume 22 Issue 2

Whole-body imaging of neuronal projections

Cai, Pan et al. developed vDISCO technology to image cellular details in intact transparent mice through bones and skin. It enabled detection of widespread CNS trauma effects and revealed short vascular connections between the skull marrow and brain meninges. The cover image shows a view of neuronal projections in the upper torso of an intact adult mouse.

See Cai et al.

Image credit: Ali Ertürk. Cover design: Marina Corral Spence.

News & Views

  • News & Views |

    In 2008, Vyazovskiy et al. published a seminal study demonstrating that sleep induces a widespread downscaling of synapses that counters the synaptic upscaling that occurred during prior wakefulness. The study laid the groundwork for current research into the ‘where’ and ‘when’ of homeostatic neuronal network regulation during sleep.

    • Niels Niethard
    •  & Jan Born
  • News & Views |

    Experience unfolds continuously in time, but we remember discrete sequences of events. In this issue of Nature Neuroscience, Montchal et al. describe brain activity patterns that predict how well people remember precisely when recent events occurred. Converging evidence suggests that homologous neural machinery structures temporal representations in rats and people.

    • Matthew L. Shapiro

Review Articles

Articles

  • Article |

    Klim et al. illuminate pathomechanisms of ALS using pluripotent stem cells to identify transcripts altered in human motor neurons by perturbations to ALS protein TDP-43, finding the microtubule regulator STMN2 highly sensitive to TDP-43 malfunctions.

    • Joseph R. Klim
    • , Luis A. Williams
    • , Francesco Limone
    • , Irune Guerra San Juan
    • , Brandi N. Davis-Dusenbery
    • , Daniel A. Mordes
    • , Aaron Burberry
    • , Michael J. Steinbaugh
    • , Kanchana K. Gamage
    • , Rory Kirchner
    • , Rob Moccia
    • , Seth H. Cassel
    • , Kuchuan Chen
    • , Brian J. Wainger
    • , Clifford J. Woolf
    •  & Kevin Eggan
  • Article |

    The mRNA encoding stathmin-2, a protein implicated in axonal growth, is shown to be widely suppressed by premature polyadenylation in both sporadic and C9orf72 ALS through a mechanism directly dependent on loss of nuclear TDP-43 in motor neurons.

    • Ze’ev Melamed
    • , Jone López-Erauskin
    • , Michael W. Baughn
    • , Ouyang Zhang
    • , Kevin Drenner
    • , Ying Sun
    • , Fernande Freyermuth
    • , Moira A. McMahon
    • , Melinda S. Beccari
    • , Jon W. Artates
    • , Takuya Ohkubo
    • , Maria Rodriguez
    • , Nianwei Lin
    • , Dongmei Wu
    • , C. Frank Bennett
    • , Frank Rigo
    • , Sandrine Da Cruz
    • , John Ravits
    • , Clotilde Lagier-Tourenne
    •  & Don W. Cleveland
  • Article |

    Loss of Trem2 function increases early amyloidogenesis by preventing microglial activation and clustering around amyloid seeds. As a consequence of reduced microglial ApoE production in the absence of Trem2 function, amyloid plaques contain less ApoE.

    • Samira Parhizkar
    • , Thomas Arzberger
    • , Matthias Brendel
    • , Gernot Kleinberger
    • , Maximilian Deussing
    • , Carola Focke
    • , Brigitte Nuscher
    • , Monica Xiong
    • , Alireza Ghasemigharagoz
    • , Natalie Katzmarski
    • , Susanne Krasemann
    • , Stefan F. Lichtenthaler
    • , Stephan A. Müller
    • , Alessio Colombo
    • , Laura Sebastian Monasor
    • , Sabina Tahirovic
    • , Jochen Herms
    • , Michael Willem
    • , Nadine Pettkus
    • , Oleg Butovsky
    • , Peter Bartenstein
    • , Dieter Edbauer
    • , Axel Rominger
    • , Ali Ertürk
    • , Stefan A. Grathwohl
    • , Jonas J. Neher
    • , David M. Holtzman
    • , Melanie Meyer-Luehmann
    •  & Christian Haass
  • Article |

    Zhou et al. show that NCORs regulate memory and synaptic plasticity through a GABAergic hypothalamus–hippocampus projection in mice, and that variants in NCOR1 and NCOR2 are linked to intellectual disability and neurodevelopmental defects in humans.

    • Wenjun Zhou
    • , Yanlin He
    • , Atteeq U Rehman
    • , Yan Kong
    • , Sungguan Hong
    • , Guolian Ding
    • , Hari Krishna Yalamanchili
    • , Ying-Wooi Wan
    • , Basil Paul
    • , Chuhan Wang
    • , Yingyun Gong
    • , Wenxian Zhou
    • , Hao Liu
    • , John Dean
    • , Emmanuel Scalais
    • , Mary O’Driscoll
    • , Jenny E. V Morton
    • , Xinguo Hou
    • , Qi Wu
    • , Qingchun Tong
    • , Zhandong Liu
    • , Pengfei Liu
    • , Yong Xu
    •  & Zheng Sun
  • Article |

    Shao et al. report that interneurons derived from iPSCs from schizophrenia patients have altered protocadherin expression and synaptic and arborization deficits. A PKC inhibitor, acting downstream of protocadherin, reversed the arborization deficit.

    • Zhicheng Shao
    • , Haneul Noh
    • , Woong Bin Kim
    • , Peiyan Ni
    • , Christine Nguyen
    • , Sarah E. Cote
    • , Elizabeth Noyes
    • , Joyce Zhao
    • , Teagan Parsons
    • , James M. Park
    • , Kelvin Zheng
    • , Joshua J. Park
    • , Joseph T. Coyle
    • , Daniel R. Weinberger
    • , Richard E. Straub
    • , Karen F. Berman
    • , Jose Apud
    • , Dost Ongur
    • , Bruce M. Cohen
    • , Donna L. McPhie
    • , Judith L. Rapoport
    • , Roy H. Perlis
    • , Thomas A. Lanz
    • , Hualin Simon Xi
    • , Changhong Yin
    • , Weihua Huang
    • , Teruyoshi Hirayama
    • , Emi Fukuda
    • , Takeshi Yagi
    • , Sulagna Ghosh
    • , Kevin C. Eggan
    • , Hae-Young Kim
    • , Leonard M. Eisenberg
    • , Alexander A. Moghadam
    • , Patric K. Stanton
    • , Jun-Hyeong Cho
    •  & Sangmi Chung
  • Article |

    Using a dynamic time-course approach to model developmental trajectories in autism spectrum disorder, Schafer et al. identified aberrant gene network dynamics as a part of an ongoing process that is primed early in development.

    • Simon T. Schafer
    • , Apua C. M. Paquola
    • , Shani Stern
    • , David Gosselin
    • , Manching Ku
    • , Monique Pena
    • , Thomas J. M. Kuret
    • , Marvin Liyanage
    • , Abed AlFatah Mansour
    • , Baptiste N. Jaeger
    • , Maria C. Marchetto
    • , Christopher K. Glass
    • , Jerome Mertens
    •  & Fred H. Gage
  • Article |

    Lieder et al show that individuals with dyslexia and individuals with ASD rely mostly on recent and earlier perceptual information, respectively, during perceptual tasks. This may explain the unique difficulties associated with the two conditions.

    • Itay Lieder
    • , Vincent Adam
    • , Or Frenkel
    • , Sagi Jaffe-Dax
    • , Maneesh Sahani
    •  & Merav Ahissar
  • Article |

    Concurrently recording neural spiking across cortical layers in a medial frontal area with EEG reveals the microcircuitry of error and reward signals, showing how neural circuits can realize executive control and produce error-related negativity.

    • Amirsaman Sajad
    • , David C. Godlove
    •  & Jeffrey D. Schall
  • Article |

    In the lateral entorhinal cortex, high-precision judgments related to timing were associated with greater blood-oxygen-level-dependent fMRI activity than low-precision time judgments. This brain region may be involved in memory for when events occur.

    • Maria E Montchal
    • , Zachariah M Reagh
    •  & Michael A Yassa
  • Article |

    Neuronal activity across task states converges onto a low-dimensional manifold. Flow within this attractor space covaries with network-level topology, fluid intelligence, and regional differences in the density of neuromodulatory receptors.

    • James M. Shine
    • , Michael Breakspear
    • , Peter T. Bell
    • , Kaylena A. Ehgoetz Martens
    • , Richard Shine
    • , Oluwasanmi Koyejo
    • , Olaf Sporns
    •  & Russell A. Poldrack
  • Article |

    Prefrontal cortex can be flexibly engaged in many different tasks. Yang et al. trained an artificial neural network to solve 20 cognitive tasks. Functionally specialized modules and compositional representations emerged in the network after training.

    • Guangyu Robert Yang
    • , Madhura R. Joglekar
    • , H. Francis Song
    • , William T. Newsome
    •  & Xiao-Jing Wang

Resources

Technical Reports

  • Technical Report |

    A nanobody-based immunolabeling method, vDISCO, boosts the signal of fluorescent proteins and allows imaging of subcellular details in intact transparent mice. It uncovers neuronal projections and skull–meninges connections in whole adult mice.

    • Ruiyao Cai
    • , Chenchen Pan
    • , Alireza Ghasemigharagoz
    • , Mihail Ivilinov Todorov
    • , Benjamin Förstera
    • , Shan Zhao
    • , Harsharan S. Bhatia
    • , Arnaldo Parra-Damas
    • , Leander Mrowka
    • , Delphine Theodorou
    • , Markus Rempfler
    • , Anna L. R. Xavier
    • , Benjamin T. Kress
    • , Corinne Benakis
    • , Hanno Steinke
    • , Sabine Liebscher
    • , Ingo Bechmann
    • , Arthur Liesz
    • , Bjoern Menze
    • , Martin Kerschensteiner
    • , Maiken Nedergaard
    •  & Ali Ertürk