Volume 22 Issue 5, May 2019

Volume 22 Issue 5

Multiplexed EM labeling

Characterizing synaptic connectivity between neurons using electron microscopy is important in drawing the ‘wiring diagram’ of the nervous system. Zhang and colleagues developed a peroxidase-based multiplexed electron microscopy labeling technique that enables simultaneous visualization of multiple cell types without the need for spectral separation, facilitating the investigation of synaptic connectivity between genetically defined neuronal populations. The cover image shows an ultrathin section from the spinal cord dorsal horn with three neuronal populations simultaneously labeled: local inhibitory interneurons (red, endoplasmic reticulum labeled), corticospinal inputs (green, cytoplasm labeled) and somatosensory primary afferents (blue, mitochondrial matrix labeled).

See Zhang et al.

Image credit: Qiyu Zhang. Cover design: Marina Corral Spence.

News & Views

  • News & Views |

    A new study reveals an unexpected mechanism underlying behavioral abnormalities in the neurodevelopmental disorder Williams syndrome. A deficit in myelination, resulting from the deletion of a Williams syndrome-associated gene in forebrain excitatory neurons, causes hypersociability by impairing action potential conduction. Accordingly, rescuing myelination or conduction normalizes this behavior.

    • Lindsay A. Osso
    •  & Jonah R. Chan
  • News & Views |

    DNA damage or cellular stresses can induce senescence, and increased senescence with aging contributes to age-associated tissue damage, inflammation and disease. Zheng and colleagues report increased senescent oligodendrocyte progenitor cells around amyloid plaques. Therapeutically eliminating these senescent cells may influence the onset and progression of Alzheimer’s disease pathology.

    • David Holtzman
    •  & Jason Ulrich
  • News & Views |

    The ventrolateral and medial orbitofrontal cortices are involved in selecting actions based on the value of expected outcomes. Malvaez and colleagues reveal that these brain regions are specialized in value encoding (ventrolateral orbitofrontal cortices) versus value memory retrieval (medial orbitofrontal cortices) and that they interact with the basolateral amygdala to orchestrate goal-oriented reward-seeking.

    • Shannon L. Gourley
  • News & Views |

    Noninvasive delivery of alternating electrical currents to temporal and prefrontal brain regions improves working memory and reverses age-related changes in brain dynamics in the elderly, report Reinhart and Nguyen in this issue of Nature Neuroscience. They also report a similar effect in young adults with poor working memory performance.

    • Romain Quentin
    •  & Leonardo G. Cohen
  • News & Views |

    Robust conclusions require rigorous statistics. In 2009 a seminal paper described the dangers and prevalence of double-dipping in neuroscience. Ten years on, I consider progress toward statistical rigor in neuroimaging.

    • Katherine S. Button

Articles

  • Article |

    Wang et al. present a computational framework integrating multi-omics data to infer key schizophrenia risk genes from GWAS data. These genes are predominantly expressed in the developing brain and are enriched for targets of approved drugs.

    • Quan Wang
    • , Rui Chen
    • , Feixiong Cheng
    • , Qiang Wei
    • , Ying Ji
    • , Hai Yang
    • , Xue Zhong
    • , Ran Tao
    • , Zhexing Wen
    • , James S. Sutcliffe
    • , Chunyu Liu
    • , Edwin H. Cook
    • , Nancy J. Cox
    •  & Bingshan Li
  • Article |

    Barak et al. show that deletion of Gtf2i, a gene deleted in Williams syndrome, from the excitatory neurons of the forebrain reduced myelin thickness and axonal conduction. Rescuing myelination with a US Food and Drug Administration-approved drug restored normal behavior.

    • Boaz Barak
    • , Zicong Zhang
    • , Yuanyuan Liu
    • , Ariel Nir
    • , Sari S. Trangle
    • , Michaela Ennis
    • , Kirsten M. Levandowski
    • , Dongqing Wang
    • , Kathleen Quast
    • , Gabriella L. Boulting
    • , Yi Li
    • , Dashzeveg Bayarsaihan
    • , Zhigang He
    •  & Guoping Feng
  • Article |

    The authors report aberrant oligodendrocyte precursor cell (OPC) interactions with blood vessels in certain multiple sclerosis lesions. These clustered OPCs can disrupt the blood–brain barrier and can impair OPC recruitment to repairing lesions.

    • Jianqin Niu
    • , Hui-Hsin Tsai
    • , Kimberly K. Hoi
    • , Nanxin Huang
    • , Guangdan Yu
    • , Kicheol Kim
    • , Sergio E. Baranzini
    • , Lan Xiao
    • , Jonah R. Chan
    •  & Stephen P. J. Fancy
  • Article |

    The Alzheimer’s disease (AD) amyloid-beta peptide causes oligodendrocyte progenitor cells to undergo senescence, contributing to neuroinflammation and cognitive impairment. Treatment of AD mice with senolytic drugs ameliorates AD neuropathologies and cognitive deficits.

    • Peisu Zhang
    • , Yuki Kishimoto
    • , Ioannis Grammatikakis
    • , Kamalvishnu Gottimukkala
    • , Roy G. Cutler
    • , Shiliang Zhang
    • , Kotb Abdelmohsen
    • , Vilhelm A. Bohr
    • , Jyoti Misra Sen
    • , Myriam Gorospe
    •  & Mark P. Mattson
  • Article |

    Using animal models and clinical samples, the authors report that glioblastoma metabolites activate the transcription factor aryl hydrocarbon receptor in tumor-associated macrophages to modulate their function and T cell immunity, promoting tumor growth.

    • Maisa C. Takenaka
    • , Galina Gabriely
    • , Veit Rothhammer
    • , Ivan D. Mascanfroni
    • , Michael A. Wheeler
    • , Chun-Cheih Chao
    • , Cristina Gutiérrez-Vázquez
    • , Jessica Kenison
    • , Emily C. Tjon
    • , Andreia Barroso
    • , Tyler Vandeventer
    • , Kalil Alves de Lima
    • , Sonja Rothweiler
    • , Lior Mayo
    • , Soufiene Ghannam
    • , Stephanie Zandee
    • , Luke Healy
    • , David Sherr
    • , Mauricio F. Farez
    • , Alexandre Prat
    • , Jack Antel
    • , David A. Reardon
    • , Hailei Zhang
    • , Simon C. Robson
    • , Gad Getz
    • , Howard L. Weiner
    •  & Francisco J. Quintana
  • Article |

    The authors have identified a subpopulation of astrocytes that is enriched in cortical layer V of the mouse cortex and is also present in the human cortex. These cells express Norrin, a protein mutated in a rare neurological degenerative disease called Norrie disease. Norrin acts on neurons to modify their morphology and activity.

    • Sean J. Miller
    • , Thomas Philips
    • , Namho Kim
    • , Raha Dastgheyb
    • , Zhuoxun Chen
    • , Yi-Chun Hsieh
    • , J. Gavin Daigle
    • , Malika Datta
    • , Jeannie Chew
    • , Svetlana Vidensky
    • , Jacqueline T. Pham
    • , Ethan G. Hughes
    • , Michael B. Robinson
    • , Rita Sattler
    • , Raju Tomer
    • , Jung Soo Suk
    • , Dwight E. Bergles
    • , Norman Haughey
    • , Mikhail Pletnikov
    • , Justin Hanes
    •  & Jeffrey D. Rothstein
  • Article |

    Lacagnina et al. show that extinction training suppresses the associated hippocampal fear engram and generates a distinct extinction engram. Reactivation of extinction engram cells reduces fear, while reactivation of fear engram cells causes fear relapse.

    • Anthony F. Lacagnina
    • , Emma T. Brockway
    • , Chelsea R. Crovetti
    • , Francis Shue
    • , Meredith J. McCarty
    • , Kevin P. Sattler
    • , Sean C. Lim
    • , Sofia Leal Santos
    • , Christine A. Denny
    •  & Michael R. Drew
  • Article |

    The value of an anticipated reward is crucial to adaptive decision-making. The authors delineate the neural circuitry supporting value encoding and retrieval, respectively, by lateral and medial orbitofrontal cortex projections to the basolateral amygdala.

    • Melissa Malvaez
    • , Christine Shieh
    • , Michael D. Murphy
    • , Venuz Y. Greenfield
    •  & Kate M. Wassum
  • Article |

    Clancy et al. investigated the relationship between individual neuron activity and cortex-wide dynamics. Neurons were diversely coupled to distal areas, and locomotion affected how neurons in different areas coupled with distal activity.

    • Kelly B. Clancy
    • , Ivana Orsolic
    •  & Thomas D. Mrsic-Flogel
  • Article |

    Fouragnan et al. used neuroimaging and ultrasound neuromodution in non-human primates to demonstrate the causal role of the anterior cingulate cortex in translating counterfactual values in future choices.

    • Elsa F. Fouragnan
    • , Bolton K. H. Chau
    • , Davide Folloni
    • , Nils Kolling
    • , Lennart Verhagen
    • , Miriam Klein-Flügge
    • , Lev Tankelevitch
    • , Georgios K. Papageorgiou
    • , Jean-Francois Aubry
    • , Jerome Sallet
    •  & Matthew F. S. Rushworth
  • Article |

    Mollink et al. establish a link between white matter microstructure and functional connectivity using MRI data from 11,354 individuals in the UK Biobank. GWAS identified genetic associations of these microstructure–function relationships.

    • Jeroen Mollink
    • , Stephen M. Smith
    • , Lloyd T. Elliott
    • , Michiel Kleinnijenhuis
    • , Marlies Hiemstra
    • , Fidel Alfaro-Almagro
    • , Jonathan Marchini
    • , Anne-Marie van Cappellen van Walsum
    • , Saad Jbabdi
    •  & Karla L. Miller

Technical Reports

Amendments & Corrections