Articles

  • Article |

    SFRP1, an ADAM10 inhibitor, is elevated in the brains of patients with Alzheimer’s disease (AD). Antibody-mediated neutralization of its activity stalls brain alterations and cognitive loss in AD-like mice, supporting SFRP1 as a potential target for disease therapy.

    • Pilar Esteve
    • , Javier Rueda-Carrasco
    • , María Inés Mateo
    • , María Jesús Martin-Bermejo
    • , Jonathan Draffin
    • , Guadalupe Pereyra
    • , África Sandonís
    • , Inmaculada Crespo
    • , Inmaculada Moreno
    • , Ester Aso
    • , Paula Garcia-Esparcia
    • , Estrella Gomez-Tortosa
    • , Alberto Rábano
    • , Juan Fortea
    • , Daniel Alcolea
    • , Alberto Lleo
    • , Michael T. Heneka
    • , José M. Valpuesta
    • , José A. Esteban
    • , Isidro Ferrer
    • , Mercedes Domínguez
    •  & Paola Bovolenta
  • Article |

    Genetic techniques to manipulate autonomic nerves in a tumor- and fiber-type-specific manner in rodent models of breast cancer reveal that sympathetic nerve denervation or parasympathetic nerve stimulation suppresses breast cancer growth and progression.

    • Atsunori Kamiya
    • , Yohsuke Hayama
    • , Shigeki Kato
    • , Akihiko Shimomura
    • , Takushi Shimomura
    • , Katsumasa Irie
    • , Ryosuke Kaneko
    • , Yuchio Yanagawa
    • , Kazuto Kobayashi
    •  & Takahiro Ochiya
  • Article |

    Parietal neurons encode the information gains that saccades are expected to bring for subsequent actions independently of economic utility, consistent with a boost in neural gain to facilitate the implementation of sampling policies.

    • Mattias Horan
    • , Nabil Daddaoua
    •  & Jacqueline Gottlieb
  • Article |

    T cell-derived interferon-γ signaling to microglia underlies spatial-learning deficits associated with West Nile virus and Zika virus via the loss of hippocampal presynaptic termini or neurons with elimination of postsynaptic termini, respectively.

    • Charise Garber
    • , Allison Soung
    • , Lauren L. Vollmer
    • , Marlene Kanmogne
    • , Aisling Last
    • , Jasmine Brown
    •  & Robyn S. Klein
  • 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 |

    This paper elucidates the mechanism regulating the subcellular localization of UBE3A and demonstrates that abrogation of UBE3A nuclear localization leads to electrophysiological and behavioral impairments in mice and to Angelman syndrome in humans.

    • Rossella Avagliano Trezza
    • , Monica Sonzogni
    • , Stijn N. V. Bossuyt
    • , F. Isabella Zampeta
    • , A. Mattijs Punt
    • , Marlene van den Berg
    • , Diana C. Rotaru
    • , Linda M. C. Koene
    • , Shashini T. Munshi
    • , Jeffrey Stedehouder
    • , Johan M. Kros
    • , Mark Williams
    • , Helen Heussler
    • , Femke M. S. de Vrij
    • , Edwin J. Mientjes
    • , Geeske M. van Woerden
    • , Steven A. Kushner
    • , Ben Distel
    •  & Ype Elgersma
  • 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 |

    Chondroitinase injections into monkey spinal cords 4 weeks after hemisection injury increased corticospinal axon growth and corticospinal synapse formation and improved functional outcomes.

    • Ephron S. Rosenzweig
    • , Ernesto A. Salegio
    • , Justine J. Liang
    • , Janet L. Weber
    • , Chase A. Weinholtz
    • , John H. Brock
    • , Rod Moseanko
    • , Stephanie Hawbecker
    • , Roger Pender
    • , Christina L. Cruzen
    • , Jennifer F. Iaci
    • , Anthony O. Caggiano
    • , Andrew R. Blight
    • , Barbara Haenzi
    • , J. Russell Huie
    • , Leif A. Havton
    • , Yvette S. Nout-Lomas
    • , James W. Fawcett
    • , Adam R. Ferguson
    • , Michael S. Beattie
    • , Jacqueline C. Bresnahan
    •  & Mark H. Tuszynski
  • 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
  • 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 |

    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
  • 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 |

    Sensory detection of prey triggers hunting actions in predators. Zhao et al. show that the zona incerta integrates prey-related multisensory signals and induces a motivational drive to guide prey detection and promote predatory attack.

    • Zheng-dong Zhao
    • , Zongming Chen
    • , Xinkuan Xiang
    • , Mengna Hu
    • , Hengchang Xie
    • , Xiaoning Jia
    • , Fang Cai
    • , Yuting Cui
    • , Zijun Chen
    • , Lechen Qian
    • , Jiashu Liu
    • , Congping Shang
    • , Yiqing Yang
    • , Xinyan Ni
    • , Wenzhi Sun
    • , Ji Hu
    • , Peng Cao
    • , Haohong Li
    •  & Wei L. Shen
  • Article |

    How does the mammalian brain trigger prey-capture behavior? Shang et al. identify a subcortical circuit that transforms prey-derived sensory cues into predatory attack signals during hunting behavior in mice.

    • Congping Shang
    • , Aixue Liu
    • , Dapeng Li
    • , Zhiyong Xie
    • , Zijun Chen
    • , Meizhu Huang
    • , Yang Li
    • , Yi Wang
    • , Wei L. Shen
    •  & Peng Cao
  • 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 (G4C2)30+ repeat expansion is the most prominent mutation in familial FTD and ALS. Here the PAF1 complex is identified as a transcriptional regulator of this unique mutation. Data from FTD tissue positive for the C9orf72 mutation support the relevance of this complex in disease.

    • Lindsey D. Goodman
    • , Mercedes Prudencio
    • , Nicholas J. Kramer
    • , Luis F. Martinez-Ramirez
    • , Ananth R. Srinivasan
    • , Matthews Lan
    • , Michael J. Parisi
    • , Yongqing Zhu
    • , Jeannie Chew
    • , Casey N. Cook
    • , Amit Berson
    • , Aaron D. Gitler
    • , Leonard Petrucelli
    •  & Nancy M. Bonini
  • Article |

    Ziegler, Hauser et al. report brain-wide, myelin-related microstructural growth from adolescence to adulthood and show that this longitudinal growth is reduced in the presence of compulsivity and impulsivity traits.

    • Gabriel Ziegler
    • , Tobias U. Hauser
    • , Michael Moutoussis
    • , Edward T. Bullmore
    • , Ian M. Goodyer
    • , Peter Fonagy
    • , Peter B. Jones
    • , Ulman Lindenberger
    •  & Raymond J. Dolan
  • Article |

    Aydin et al. show that the proneural factors Ascl1 and Neurog2 bind to largely non-overlapping sites in the genome, establishing distinct chromatin landscapes that shape the activity of downstream factors during neuronal fate specification.

    • Begüm Aydin
    • , Akshay Kakumanu
    • , Mary Rossillo
    • , Mireia Moreno-Estellés
    • , Görkem Garipler
    • , Niels Ringstad
    • , Nuria Flames
    • , Shaun Mahony
    •  & Esteban O. Mazzoni
  • Article |

    The authors generated a mouse model of C9ORF72-related amyotrophic lateral sclerosis and frontotemporal dementia based on dipeptide repeat proteins and report that defects in mitochondria may contribute to disease pathogenesis.

    • So Yoen Choi
    • , Rodrigo Lopez-Gonzalez
    • , Gopinath Krishnan
    • , Hannah L. Phillips
    • , Alissa Nana Li
    • , William W. Seeley
    • , Wei-Dong Yao
    • , Sandra Almeida
    •  & Fen-Biao Gao
  • Article |

    Lu et al. report a pathway that reprograms protein quality control under stress. Identified in a Caenorhabditis elegans screen and characterized in mammalian systems, L3MBTL1 and its partner SETD8 modulate proteotoxicity and are deregulated in patients with ALS/FTD.

    • Jiayin Lu
    • , Goran Periz
    • , Yu-Ning Lu
    • , Qing Tang
    • , Yang Liu
    • , Tao Zhang
    • , Yajas Shah
    • , Ravi Thombre
    • , Reham Aljumaah
    • , Weixin Li
    • , Jelena Mojsilovic-Petrovic
    • , Yon Ji
    • , Kenji Johnson
    • , Robert Kalb
    •  & Jiou Wang
  • Article |

    Pairing an odor conditioned stimulus (CS) with an unconditioned stimulus (US) induces memory formation. Vetere et al. replace the real CS and US with direct optogenetic stimulation of the brain and create a fully artificial odor memory in mice.

    • Gisella Vetere
    • , Lina M. Tran
    • , Sara Moberg
    • , Patrick E. Steadman
    • , Leonardo Restivo
    • , Filomene G. Morrison
    • , Kerry J. Ressler
    • , Sheena A. Josselyn
    •  & Paul W. Frankland
  • Article |

    The brain predicts future sensory input. The authors hypothesize that the visual system achieves this by straightening the temporal trajectories of natural videos, and they provide evidence using human perceptual experiments and computational modeling.

    • Olivier J. Hénaff
    • , Robbe L. T. Goris
    •  & Eero P. Simoncelli
  • Article |

    Dong, Wang et al. uncover a circuit linking Glu+cingulate inputs→PV+ neurons in the limbic thalamic reticular nucleus→intermediodorsal thalamic nucleus, and show that this cortico-intrathalamic circuit is a component of the fear circuitry and controls flight behavior in mice.

    • Ping Dong
    • , Hao Wang
    • , Xiao-Fan Shen
    • , Ping Jiang
    • , Xu-Tao Zhu
    • , Yue Li
    • , Jia-Hao Gao
    • , Shan Lin
    • , Yue Huang
    • , Xiao-Bin He
    • , Fu-Qiang Xu
    • , Shumin Duan
    • , Hong Lian
    • , Hao Wang
    • , Jiadong Chen
    •  & Xiao-Ming 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 discover neurons in the human prefrontal cortex that encode subjective decisions and that may underlie the process by which opinions are formed. They also find how disruption of these neurons selectively interferes with the decision-making process.

    • Mohsen Jamali
    • , Ben Grannan
    • , Keren Haroush
    • , Ziev B. Moses
    • , Emad N. Eskandar
    • , Todd Herrington
    • , Shaun Patel
    •  & Ziv M. Williams
  • Article |

    The authors report that the presynaptic protein bassoon forms toxic aggregates in neuronal somata in multiple sclerosis. Stimulation of proteasomal activity reduces bassoon aggregates, neuroaxonal loss and disability during CNS inflammation.

    • Benjamin Schattling
    • , Jan Broder Engler
    • , Constantin Volkmann
    • , Nicola Rothammer
    • , Marcel S. Woo
    • , Meike Petersen
    • , Iris Winkler
    • , Max Kaufmann
    • , Sina C. Rosenkranz
    • , Anna Fejtova
    • , Ulrich Thomas
    • , Aparajita Bose
    • , Simone Bauer
    • , Simone Träger
    • , Katharine K. Miller
    • , Wolfgang Brück
    • , Kent E. Duncan
    • , Gabriela Salinas
    • , Peter Soba
    • , Eckart D. Gundelfinger
    • , Doron Merkler
    •  & Manuel A. Friese
  • 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 |

    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
  • 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 |

    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 |

    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 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 |

    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 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 |

    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 |

    Using a behaviorally obtained reference point to compute social value, Ma et al. show that social-value distance is encoded by the amygdala in prosocials. Oxytocin amplifies this amygdala representation and increases prosociality in individualists.

    • Yunzhe Liu
    • , Shiyi Li
    • , Wanjun Lin
    • , Wenxin Li
    • , Xinyuan Yan
    • , Xuena Wang
    • , Xinyue Pan
    • , Robb B. Rutledge
    •  & Yina Ma
  • Article |

    Using a novel assay, Ellis et al. show that stem cell-derived neurons from individuals with autism carrying SHANK2 mutations are hyperconnected, have impaired activity-dependent dendrite extension, and have perturbed transcription of ASD gene modules.

    • Kirill Zaslavsky
    • , Wen-Bo Zhang
    • , Fraser P. McCready
    • , Deivid C. Rodrigues
    • , Eric Deneault
    • , Caitlin Loo
    • , Melody Zhao
    • , P. Joel Ross
    • , Joelle El Hajjar
    • , Asli Romm
    • , Tadeo Thompson
    • , Alina Piekna
    • , Wei Wei
    • , Zhuozhi Wang
    • , Shahryar Khattak
    • , Marat Mufteev
    • , Peter Pasceri
    • , Stephen W. Scherer
    • , Michael W. Salter
    •  & James Ellis