Volume 22 Issue 7, July 2019

Volume 22 Issue 7

Microglia rebirth drives CNS remyelination

The regeneration of myelin following damage in various neurodegenerative disorders contributes to restoration of axonal health and function. Lloyd and colleagues reveal that remyelination requires the death of pro-inflammatory microglia by necroptosis, followed by repopulation by pro-regenerative microglia. The cover art image depicts a phoenix, a long-lived bird from Greek mythology that rises from the ashes following death to regenerate.

See Miron et al.

Image credit: Amy Lloyd using BioRender software. Cover design: Marina Corral Spence.

News & Views

  • News & Views |

    A new study by Owen et al. shows that widely used optogenetic light delivery can heat brain tissue and produce changes in neural activity and behavior in the absence of opsins. How will this finding influence experimental design in the optical age of neuroscience?

    • Daniel F. Cardozo Pinto
    •  & Stephan Lammel
  • News & Views |

    The creation of a murine Cre driver specific to CNS capillary pericytes has opened a major bottleneck in brain microvascular research. Using this tool, pericyte loss in the adult brain is shown to induce neuronal loss due to concurrent microcirculatory failure and depletion of the protective trophic factor pleiotrophin.

    • Andrée-Anne Berthiaume
    •  & Andy Y. Shih
  • News & Views |

    Shahmoradian and colleagues report that the structure of Lewy bodies in Parkinson’s disease consists of α-synuclein and lipid vesicle clusters instead of the long-assumed amyloid fibril core. This finding has implications for our understanding of the underlying pathogenesis of synucleinopathies.

    • Tim Bartels

Brief Communications

  • Brief Communication |

    Lloyd et al. find that regeneration of CNS myelin requires death of proinflammatory microglia followed by repopulation to a pro-regenerative state, revealing new therapeutic targets for neurodegenerative disease.

    • Amy F. Lloyd
    • , Claire L. Davies
    • , Rebecca K. Holloway
    • , Yasmine Labrak
    • , Graeme Ireland
    • , Dario Carradori
    • , Alessandra Dillenburg
    • , Eva Borger
    • , Daniel Soong
    • , Jill C. Richardson
    • , Tanja Kuhlmann
    • , Anna Williams
    • , Jeffrey W. Pollard
    • , Anne des Rieux
    • , Josef Priller
    •  & Veronique E. Miron
  • Brief Communication |

    The authors show that decreased synaptic efficacy onto raphe-projecting lateral habenula neurons supports opiate withdrawal-induced sociability deficits, and they demonstrate a role for TNF-α signaling in this process.

    • Kristina Valentinova
    • , Anna Tchenio
    • , Massimo Trusel
    • , Joseph A. Clerke
    • , Arnaud L. Lalive
    • , Stamatina Tzanoulinou
    • , Alessandro Matera
    • , Imane Moutkine
    • , Luc Maroteaux
    • , Rosa C. Paolicelli
    • , Andrea Volterra
    • , Camilla Bellone
    •  & Manuel Mameli
  • Brief Communication |

    Optogenetics has revolutionized neuroscience, but intracranial illumination can cause off-target effects. Owen et al. identify a temperature-sensitive potassium current that modulates neuronal activity and behavior independent of opsin expression.

    • Scott F. Owen
    • , Max H. Liu
    •  & Anatol C. Kreitzer

Articles

  • Article |

    The study reports a genome-wide significant locus for cannabis use disorder, replicating in an independent cohort, and implicates CHRNA2, which encodes an acetylcholine receptor subunit, in the disorder by analyses of genetically regulated gene expression.

    • Ditte Demontis
    • , Veera Manikandan Rajagopal
    • , Thorgeir E. Thorgeirsson
    • , Thomas D. Als
    • , Jakob Grove
    • , Kalle Leppälä
    • , Daniel F. Gudbjartsson
    • , Jonatan Pallesen
    • , Carsten Hjorthøj
    • , Gunnar W. Reginsson
    • , Thorarinn Tyrfingsson
    • , Valgerdur Runarsdottir
    • , Per Qvist
    • , Jane Hvarregaard Christensen
    • , Jonas Bybjerg-Grauholm
    • , Marie Bækvad-Hansen
    • , Laura M. Huckins
    • , Eli A. Stahl
    • , Allan Timmermann
    • , Esben Agerbo
    • , David M. Hougaard
    • , Thomas Werge
    • , Ole Mors
    • , Preben Bo Mortensen
    • , Merete Nordentoft
    • , Mark J. Daly
    • , Hreinn Stefansson
    • , Kari Stefansson
    • , Mette Nyegaard
    •  & Anders D. Børglum

    Nature Outlook:

  • Article |

    Microglia are resident immune cells of the CNS. Here the authors show that neurons communicate to microglia via activity-dependent fractalkine and ADAM10 signaling to induce removal of synapses in the brain after sensory loss.

    • Georgia Gunner
    • , Lucas Cheadle
    • , Kasey M. Johnson
    • , Pinar Ayata
    • , Ana Badimon
    • , Erica Mondo
    • , M. Aurel Nagy
    • , Liwang Liu
    • , Shane M. Bemiller
    • , Ki-Wook Kim
    • , Sergio A. Lira
    • , Bruce T. Lamb
    • , Andrew R. Tapper
    • , Richard M. Ransohoff
    • , Michael E. Greenberg
    • , Anne Schaefer
    •  & Dorothy P. Schafer
  • Article |

    Using pericyte-specific Cre and ablation mouse lines, the authors show that loss of brain pericytes leads to circulatory failure and reduced pleiotrophin causing rapid neuron loss. These findings link pericyte loss to a rapid neurodegeneration cascade.

    • Angeliki M. Nikolakopoulou
    • , Axel Montagne
    • , Kassandra Kisler
    • , Zhonghua Dai
    • , Yaoming Wang
    • , Mikko T. Huuskonen
    • , Abhay P. Sagare
    • , Divna Lazic
    • , Melanie D. Sweeney
    • , Pan Kong
    • , Min Wang
    • , Nelly Chuqui Owens
    • , Erica J. Lawson
    • , Xiaochun Xie
    • , Zhen Zhao
    •  & Berislav V. Zlokovic
  • Article |

    Using three-dimensional correlative light and electron microscopy of Lewy bodies and Lewy neurites in postmortem brains of Parkinson’s disease patients, researchers show that the major constituents are membranes rather than proteinaceous filaments.

    • Sarah H. Shahmoradian
    • , Amanda J. Lewis
    • , Christel Genoud
    • , Jürgen Hench
    • , Tim E. Moors
    • , Paula P. Navarro
    • , Daniel Castaño-Díez
    • , Gabriel Schweighauser
    • , Alexandra Graff-Meyer
    • , Kenneth N. Goldie
    • , Rosmarie Sütterlin
    • , Evelien Huisman
    • , Angela Ingrassia
    • , Yvonne de Gier
    • , Annemieke J. M. Rozemuller
    • , Jing Wang
    • , Anne De Paepe
    • , Johannes Erny
    • , Andreas Staempfli
    • , Joerg Hoernschemeyer
    • , Frederik Großerüschkamp
    • , Daniel Niedieker
    • , Samir F. El-Mashtoly
    • , Marialuisa Quadri
    • , Wilfred F. J. Van IJcken
    • , Vincenzo Bonifati
    • , Klaus Gerwert
    • , Bernd Bohrmann
    • , Stephan Frank
    • , Markus Britschgi
    • , Henning Stahlberg
    • , Wilma D. J. Van de Berg
    •  & Matthias E. Lauer
  • Article |

    Namboodiri, Otis et al. reveal that orbitofrontal cortex acquires and maintains a long-term memory of cue–reward associations to guide multiple aspects of behavioral learning, and that it routes select information to a downstream learning center.

    • Vijay Mohan K. Namboodiri
    • , James M. Otis
    • , Kay van Heeswijk
    • , Elisa S. Voets
    • , Rizk A. Alghorazi
    • , Jose Rodriguez-Romaguera
    • , Stefan Mihalas
    •  & Garret D. Stuber
  • Article |

    Different body parts must be coordinated to perform skills. Lemke et al. report that distinct patterns of brain activity emerge during learning related to each body part and conclude that such patterns are refined independently yet function together.

    • Stefan M. Lemke
    • , Dhakshin S. Ramanathan
    • , Ling Guo
    • , Seok Joon Won
    •  & Karunesh Ganguly
  • Article |

    Synapses of retinal bipolar cells encode contrast through changes in both the frequency and amplitude of release events. The amplitude code contains symbols up to 11 vesicle equivalents and increases the efficiency of information transmission.

    • Ben James
    • , Léa Darnet
    • , José Moya-Díaz
    • , Sofie-Helene Seibel
    •  & Leon Lagnado
  • Article |

    The role of persistent spiking activity in working memory has recently come under debate. Here the authors use biologically realistic recurrent neural networks to explain why the strength of persistent activity can vary markedly between tasks.

    • Nicolas Y. Masse
    • , Guangyu R. Yang
    • , H. Francis Song
    • , Xiao-Jing Wang
    •  & David J. Freedman

Resources

  • Resource |

    Gouwens et al. established a morpho-electrical taxonomy of cell types for the mouse visual cortex via unsupervised clustering analysis of multiple quantitative features from 1,938 neurons available online at the Allen Cell Types Database.

    • Nathan W. Gouwens
    • , Staci A. Sorensen
    • , Jim Berg
    • , Changkyu Lee
    • , Tim Jarsky
    • , Jonathan Ting
    • , Susan M. Sunkin
    • , David Feng
    • , Costas A. Anastassiou
    • , Eliza Barkan
    • , Kris Bickley
    • , Nicole Blesie
    • , Thomas Braun
    • , Krissy Brouner
    • , Agata Budzillo
    • , Shiella Caldejon
    • , Tamara Casper
    • , Dan Castelli
    • , Peter Chong
    • , Kirsten Crichton
    • , Christine Cuhaciyan
    • , Tanya L. Daigle
    • , Rachel Dalley
    • , Nick Dee
    • , Tsega Desta
    • , Song-Lin Ding
    • , Samuel Dingman
    • , Alyse Doperalski
    • , Nadezhda Dotson
    • , Tom Egdorf
    • , Michael Fisher
    • , Rebecca A. de Frates
    • , Emma Garren
    • , Marissa Garwood
    • , Amanda Gary
    • , Nathalie Gaudreault
    • , Keith Godfrey
    • , Melissa Gorham
    • , Hong Gu
    • , Caroline Habel
    • , Kristen Hadley
    • , James Harrington
    • , Julie A. Harris
    • , Alex Henry
    • , DiJon Hill
    • , Sam Josephsen
    • , Sara Kebede
    • , Lisa Kim
    • , Matthew Kroll
    • , Brian Lee
    • , Tracy Lemon
    • , Katherine E. Link
    • , Xiaoxiao Liu
    • , Brian Long
    • , Rusty Mann
    • , Medea McGraw
    • , Stefan Mihalas
    • , Alice Mukora
    • , Gabe J. Murphy
    • , Lindsay Ng
    • , Kiet Ngo
    • , Thuc Nghi Nguyen
    • , Philip R. Nicovich
    • , Aaron Oldre
    • , Daniel Park
    • , Sheana Parry
    • , Jed Perkins
    • , Lydia Potekhina
    • , David Reid
    • , Miranda Robertson
    • , David Sandman
    • , Martin Schroedter
    • , Cliff Slaughterbeck
    • , Gilberto Soler-Llavina
    • , Josef Sulc
    • , Aaron Szafer
    • , Bosiljka Tasic
    • , Naz Taskin
    • , Corinne Teeter
    • , Nivretta Thatra
    • , Herman Tung
    • , Wayne Wakeman
    • , Grace Williams
    • , Rob Young
    • , Zhi Zhou
    • , Colin Farrell
    • , Hanchuan Peng
    • , Michael J. Hawrylycz
    • , Ed Lein
    • , Lydia Ng
    • , Anton Arkhipov
    • , Amy Bernard
    • , John W. Phillips
    • , Hongkui Zeng
    •  & Christof Koch

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