Browse Articles

  • Article |

    A genetic study of problematic alcohol use in 435,563 individuals, including data from the Million Veteran Program, Psychiatric Genomics Consortium and UK Biobank, found many novel risk loci and provided new insights into trait biology.

    • Hang Zhou
    • , Julia M. Sealock
    • , Sandra Sanchez-Roige
    • , Toni-Kim Clarke
    • , Daniel F. Levey
    • , Zhongshan Cheng
    • , Boyang Li
    • , Renato Polimanti
    • , Rachel L. Kember
    • , Rachel Vickers Smith
    • , Johan H. Thygesen
    • , Marsha Y. Morgan
    • , Stephen R. Atkinson
    • , Mark R. Thursz
    • , Mette Nyegaard
    • , Manuel Mattheisen
    • , Anders D. Børglum
    • , Emma C. Johnson
    • , Amy C. Justice
    • , Abraham A. Palmer
    • , Andrew McQuillin
    • , Lea K. Davis
    • , Howard J. Edenberg
    • , Arpana Agrawal
    • , Henry R. Kranzler
    •  & Joel Gelernter
  • Article |

    Assessing residual consciousness in unresponsive patients is a major clinical concern. Gui et al. demonstrate that EEG-based language assessment can objectively characterize states of consciousness and predict outcomes in individual patients.

    • Peng Gui
    • , Yuwei Jiang
    • , Di Zang
    • , Zengxin Qi
    • , Jiaxing Tan
    • , Hiromi Tanigawa
    • , Jian Jiang
    • , Yunqing Wen
    • , Long Xu
    • , Jizong Zhao
    • , Ying Mao
    • , Mu-ming Poo
    • , Nai Ding
    • , Stanislas Dehaene
    • , Xuehai Wu
    •  & Liping Wang
  • Article |

    This study elucidates how long-range chromatin loops are altered during short- and long-term changes in neural activity, and analyzes the interplay between the 3D genome and the linear epigenome during activity-dependent transcriptional responses.

    • Jonathan A. Beagan
    • , Elissa D. Pastuzyn
    • , Lindsey R. Fernandez
    • , Michael H. Guo
    • , Kelly Feng
    • , Katelyn R. Titus
    • , Harshini Chandrashekar
    • , Jason D. Shepherd
    •  & Jennifer E. Phillips-Cremins
  • Article |

    Shen et al. report that prolonged obesity is associated with cerebrovascular dysfunction and Tak1 activation in brainstem microglia. Pharmacological inhibition or genetic depletion of Tak1 restores cerebrovascular function in obese mice.

    • Qing Shen
    • , Zhuo Chen
    • , Faming Zhao
    • , Susu Pan
    • , Tingting Zhang
    • , Xueer Cheng
    • , Lei Zhang
    • , Shanshan Zhang
    • , Junxia Qi
    • , Juxue Li
    • , Dongsheng Cai
    •  & Guo Zhang
  • News & Views |

    Hardening of the arteries (atherosclerosis) was linked to dementia long ago, but subsequently, Alzheimer’s plaques and tangles have received more attention. A new proteome-wide association study unveils molecular links between intracranial atherosclerosis and dementia, independent of other pathologies, providing new evidence for one of the oldest suspected causes of dementia.

    • Costantino Iadecola
  • News & Views |

    General anesthetics during surgery are presumed to block pain by dampening brain activity and promoting loss-of-consciousness. A new study shows that anesthetics activate an endogenous analgesia neural ensemble in the central nucleus of the amygdala.

    • Nora M. McCall
    • , Jessica A. Wojick
    •  & Gregory Corder
  • Article |

    Hua and Chen et al. show that general anesthesia activates a distinct population of central amygdala neurons and that these neurons can potently suppress pain responses through their widespread projections to many pain-processing centers in the brain.

    • Thuy Hua
    • , Bin Chen
    • , Dongye Lu
    • , Katsuyasu Sakurai
    • , Shengli Zhao
    • , Bao-Xia Han
    • , Jiwoo Kim
    • , Luping Yin
    • , Yong Chen
    • , Jinghao Lu
    •  & Fan Wang
  • Brief Communication |

    Proteome-wide association studies of brain samples from older adults revealed effects of cerebral atherosclerosis and Alzheimer’s disease. A subset of proteins and protein co-expression modules were associated with both, suggesting shared mechanisms.

    • Aliza P. Wingo
    • , Wen Fan
    • , Duc M. Duong
    • , Ekaterina S. Gerasimov
    • , Eric B. Dammer
    • , Yue Liu
    • , Nadia V. Harerimana
    • , Bartholomew White
    • , Madhav Thambisetty
    • , Juan C. Troncoso
    • , Namhee Kim
    • , Julie A. Schneider
    • , Ihab M. Hajjar
    • , James J. Lah
    • , David A. Bennett
    • , Nicholas T. Seyfried
    • , Allan I. Levey
    •  & Thomas S. Wingo
  • Brief Communication |

    Greater novelty and diversity in one’s daily physical environment is associated with positive affect, and functional connectivity within a hippocampal–striatal circuit is related to the strength of this effect.

    • Aaron S. Heller
    • , Tracey C. Shi
    • , C. E. Chiemeka Ezie
    • , Travis R. Reneau
    • , Lara M. Baez
    • , Conor J. Gibbons
    •  & Catherine A. Hartley
  • Article |

    Precisely timed motor learning promotes remyelination in the motor cortex by enhancing oligodendrogenesis and stimulating mature oligodendrocytes to generate new myelin, presenting mature oligodendrocytes as new targets in remyelinating therapies.

    • Clara M. Bacmeister
    • , Helena J. Barr
    • , Crystal R. McClain
    • , Michael A. Thornton
    • , Dailey Nettles
    • , Cristin G. Welle
    •  & Ethan G. Hughes
  • Article |

    Medulloblastomas lacking p53 do not express surface class I major histocompatibility complex (MHC-I) and are resistant to immune rejection. Tumor necrosis factor rescues MHC-I expression and synergizes with immune checkpoint inhibitors to promote rejection.

    • Alexandra Garancher
    • , Hiromichi Suzuki
    • , Svasti Haricharan
    • , Lianne Q. Chau
    • , Meher Beigi Masihi
    • , Jessica M. Rusert
    • , Paula S. Norris
    • , Florent Carrette
    • , Megan M. Romero
    • , Sorana A. Morrissy
    • , Patryk Skowron
    • , Florence M. G. Cavalli
    • , Hamza Farooq
    • , Vijay Ramaswamy
    • , Steven J. M. Jones
    • , Richard A. Moore
    • , Andrew J. Mungall
    • , Yussanne Ma
    • , Nina Thiessen
    • , Yisu Li
    • , Alaide Morcavallo
    • , Lin Qi
    • , Mari Kogiso
    • , Yuchen Du
    • , Patricia Baxter
    • , Jacob J. Henderson
    • , John R. Crawford
    • , Michael L. Levy
    • , James M. Olson
    • , Yoon-Jae Cho
    • , Aniruddha J. Deshpande
    • , Xiao-Nan Li
    • , Louis Chesler
    • , Marco A. Marra
    • , Harald Wajant
    • , Oren J. Becher
    • , Linda M. Bradley
    • , Carl F. Ware
    • , Michael D. Taylor
    •  & Robert J. Wechsler-Reya
  • News & Views |

    One hallmark of sleep is the slow oscillation, which is often synchronous across the neocortical mantle. How this synchrony is achieved remains unclear. A new study by Narikiyo et al. demonstrates how the claustrum may play a key role in the global control of this rhythm.

    • Igor Timofeev
    •  & Sylvain Chauvette
  • Article |

    The authors establish the claustrum-Cre transgenic mouse line and demonstrate that the claustrum orchestrates cortical slow-wave activity by synchronously driving the inhibitory interneurons in widespread cortical areas.

    • Kimiya Narikiyo
    • , Rumiko Mizuguchi
    • , Ayako Ajima
    • , Momoko Shiozaki
    • , Hiroki Hamanaka
    • , Joshua P. Johansen
    • , Kensaku Mori
    •  & Yoshihiro Yoshihara
  • Article |

    Cregg et al. find that a specific population of brainstem neurons act to control left–right turning of locomotor movements in mammals through distinct axial- and limb-based mechanisms. This turning pathway is the dominant system for natural directional movements.

    • Jared M. Cregg
    • , Roberto Leiras
    • , Alexia Montalant
    • , Paulina Wanken
    • , Ian R. Wickersham
    •  & Ole Kiehn
  • Article |

    Marshall et al. show that regions of the genome adopt a noncanonical Z-DNA state in the prefrontal cortex in response to fear learning and that binding of Adar1 reduces Z-DNA during extinction learning, which is required for memory flexibility.

    • Paul R. Marshall
    • , Qiongyi Zhao
    • , Xiang Li
    • , Wei Wei
    • , Ambika Periyakaruppiah
    • , Esmi L. Zajaczkowski
    • , Laura J. Leighton
    • , Sachithrani U. Madugalle
    • , Dean Basic
    • , Ziqi Wang
    • , Jiayu Yin
    • , Wei-Siang Liau
    • , Ankita Gupte
    • , Carl R. Walkley
    •  & Timothy W. Bredy
  • Brief Communication |

    A new subset of disease-associated astrocytes (DAAs) is identified in a mouse model of Alzheimer’s disease by single-nucleus RNA sequencing. DAAs are also found in aged wild-type mice, suggesting a link to genetic and age-related factors.

    • Naomi Habib
    • , Cristin McCabe
    • , Sedi Medina
    • , Miriam Varshavsky
    • , Daniel Kitsberg
    • , Raz Dvir-Szternfeld
    • , Gilad Green
    • , Danielle Dionne
    • , Lan Nguyen
    • , Jamie L. Marshall
    • , Fei Chen
    • , Feng Zhang
    • , Tommy Kaplan
    • , Aviv Regev
    •  & Michal Schwartz
  • Resource |

    Single-nucleus transcriptomics reveal brain alterations associated with major depression. Deep layer excitatory cells and immature oligodendrocytes showed most changes, involving synaptic plasticity, immune function and steroid hormones.

    • Corina Nagy
    • , Malosree Maitra
    • , Arnaud Tanti
    • , Matthew Suderman
    • , Jean-Francois Théroux
    • , Maria Antonietta Davoli
    • , Kelly Perlman
    • , Volodymyr Yerko
    • , Yu Chang Wang
    • , Shreejoy J. Tripathy
    • , Paul Pavlidis
    • , Naguib Mechawar
    • , Jiannis Ragoussis
    •  & Gustavo Turecki
  • Obituary
    | Open Access

    Ronald S. Duman, the Elizabeth Mears and House Jameson Professor of Psychiatry, Professor of Neuroscience at the Yale University School of Medicine and Director of the Abraham Ribicoff Research Facilities of the Connecticut Mental Health Center, died unexpectedly of a heart attack on 1 February 2020 while hiking near his home in Guilford, CT. Dr Duman was about to turn 65 years old. He was a member of the US National Academy of Medicine and received many honors for his research on mood disorders, including the Colvin Prize, from the Brain and Behavior Research Foundation, and the Anna-Monika Foundation Prize.

    • Jane R. Taylor
    • , Ralph J. DiLeone
    •  & Marina R. Picciotto
  • News & Views |

    At the heart of C9ORF72-related amyotrophic lateral sclerosis and frontotemporal dementia (ALS /FTD) research lies the mechanistic question of whether disease is caused by toxic gain of function related to the repeat expansion, loss of endogenous C9ORF72 expression, or both. New findings provide insights to this question.

    • Cathleen Lutz
  • Brief Communication |

    Balezeau et al. find a primate homolog of the human language pathway within the auditory system of monkeys and apes. This discovery pushes back the human language pathway’s origin by about 20 million years and illuminates its remarkable evolutionary transformation.

    • Fabien Balezeau
    • , Benjamin Wilson
    • , Guillermo Gallardo
    • , Fred Dick
    • , William Hopkins
    • , Alfred Anwander
    • , Angela D. Friederici
    • , Timothy D. Griffiths
    •  & Christopher I. Petkov
  • Article |

    The authors describe a thalamic population, innervated by multimodal brainstem inputs, that forms a CS–US association prior to the lateral amygdala. Its fast and plastic signal defines an amygdala activity pattern necessary for adaptive fear learning.

    • Boglárka Barsy
    • , Kinga Kocsis
    • , Aletta Magyar
    • , Ákos Babiczky
    • , Mónika Szabó
    • , Judit M. Veres
    • , Dániel Hillier
    • , István Ulbert
    • , Ofer Yizhar
    •  & Ferenc Mátyás
  • Article |

    Flanigan et al. show that activation of inhibitory neurons in the lateral habenula by the neuropeptide orexin (hypocretin) promotes both inter-male aggression and conditioned place preference for contexts associated with winning aggressive contests.

    • Meghan E. Flanigan
    • , Hossein Aleyasin
    • , Long Li
    • , C. Joseph Burnett
    • , Kenny L. Chan
    • , Katherine B. LeClair
    • , Elizabeth K. Lucas
    • , Bridget Matikainen-Ankney
    • , Romain Durand-de Cuttoli
    • , Aki Takahashi
    • , Caroline Menard
    • , Madeline L. Pfau
    • , Sam A. Golden
    • , Sylvain Bouchard
    • , Erin S. Calipari
    • , Eric J. Nestler
    • , Ralph J. DiLeone
    • , Akihiro Yamanaka
    • , George W. Huntley
    • , Roger L. Clem
    •  & Scott J. Russo
  • Article |

    Lopez-Persem et al. used intracranial recordings in people with epilepsy to uncover key functional properties of neural value signals that might explain irrational choice behavior.

    • Alizée Lopez-Persem
    • , Julien Bastin
    • , Mathilde Petton
    • , Raphaëlle Abitbol
    • , Katia Lehongre
    • , Claude Adam
    • , Vincent Navarro
    • , Sylvain Rheims
    • , Philippe Kahane
    • , Philippe Domenech
    •  & Mathias Pessiglione
  • Resource |

    The authors identify two subsets of peripheral nerve macrophages residing in the endoneurium and the epineurium and displaying a distinct transcriptome and response to injury. These cells lack the main microglia identity and have a distinct origin.

    • Elke Ydens
    • , Lukas Amann
    • , Bob Asselbergh
    • , Charlotte L. Scott
    • , Liesbet Martens
    • , Dorine Sichien
    • , Omar Mossad
    • , Thomas Blank
    • , Sofie De Prijck
    • , Donovan Low
    • , Takahiro Masuda
    • , Yvan Saeys
    • , Vincent Timmerman
    • , Ralf Stumm
    • , Florent Ginhoux
    • , Marco Prinz
    • , Sophie Janssens
    •  & Martin Guilliams
  • Article |

    The most common genetic cause of ALS and frontal temporal dementia—hexanucleotide repeat expansion in C9orf72—is shown to provoke disease via synergy of gain of toxicity(ies) from repeat-encoded RNAs/dipeptide repeat proteins and reduction in the C9ORF72 protein.

    • Qiang Zhu
    • , Jie Jiang
    • , Tania F. Gendron
    • , Melissa McAlonis-Downes
    • , Lulin Jiang
    • , Amy Taylor
    • , Sandra Diaz Garcia
    • , Somasish Ghosh Dastidar
    • , Maria J. Rodriguez
    • , Patrick King
    • , Yongjie Zhang
    • , Albert R. La Spada
    • , Huaxi Xu
    • , Leonard Petrucelli
    • , John Ravits
    • , Sandrine Da Cruz
    • , Clotilde Lagier-Tourenne
    •  & Don W. Cleveland
  • Review Article |

    The increasing use of cannabis has brought significant attention to cannabis use disorder (CUD) and its neurobiological underpinnings. Here Ferland and Hurd discuss risk factors related to the development of CUD its neurobiological characteristics.

    • Jacqueline-Marie N. Ferland
    •  & Yasmin L. Hurd
  • Article |

    Hippocampal neurons track events as abstract units of episodic experience. These event representations can be transferred between different experiences and are separately manipulable from hippocampal representations of continuous changes in space.

    • Chen Sun
    • , Wannan Yang
    • , Jared Martin
    •  & Susumu Tonegawa
  • News & Views |

    A new study shows that mapping neural signals directly to word sequences produces lower error rates in speech decoding than previous methods that use motor or auditory based features. This suggests that using higher-level language goals can aid decoding algorithms for neural speech prostheses.

    • Gregory B. Cogan
  • Obituary |

    On 2 January 2020, the neuroscience community lost not only a pioneering figure, but also a generous and influential thought leader. Bruce Sherman McEwen, head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at the Rockefeller University, passed away at age 81, following a short illness. A member of the National Academy of Sciences, National Academy of Medicine and American Academy of Arts & Sciences, and former president of the Society for Neuroscience, Bruce will be remembered for his profound scientific impact, measured not only by output of papers, but also by the large family of neuroscientists he trained over a career spanning nearly six decades. Above all, Bruce will be remembered for his generosity, kindness, gentleness of soul, and for being an extraordinary mentor.

    • Matthew N. Hill
    • , Ilia N. Karatsoreos
    • , E. Ron de Kloet
    • , Sonia Lupien
    •  & Catherine S. Woolley
  • Article |

    Eschbach, Fushiki et al. combine synaptic-resolution circuit mapping, functional analyses and modeling to reveal circuit motifs that regulate dopaminergic neuron activity and may increase associative learning task performance and flexibility.

    • Claire Eschbach
    • , Akira Fushiki
    • , Michael Winding
    • , Casey M. Schneider-Mizell
    • , Mei Shao
    • , Rebecca Arruda
    • , Katharina Eichler
    • , Javier Valdes-Aleman
    • , Tomoko Ohyama
    • , Andreas S. Thum
    • , Bertram Gerber
    • , Richard D. Fetter
    • , James W. Truman
    • , Ashok Litwin-Kumar
    • , Albert Cardona
    •  & Marta Zlatic
  • Article |

    Jaffe et al. profile the granule cell layer of the human hippocampus and find unique molecular associations for aging and genetic variation, as well as diagnosis with schizophrenia and its genetic risk, that were previously undiscovered in homogenate tissue.

    • Andrew E. Jaffe
    • , Daniel J. Hoeppner
    • , Takeshi Saito
    • , Lou Blanpain
    • , Joy Ukaigwe
    • , Emily E. Burke
    • , Leonardo Collado-Torres
    • , Ran Tao
    • , Katsunori Tajinda
    • , Kristen R. Maynard
    • , Matthew N. Tran
    • , Keri Martinowich
    • , Amy Deep-Soboslay
    • , Joo Heon Shin
    • , Joel E. Kleinman
    • , Daniel R. Weinberger
    • , Mitsuyuki Matsumoto
    •  & Thomas M. Hyde
  • Article |

    A new spatial transcriptomic approach reveals astrocyte heterogeneity across layers of the mammalian cerebral cortex. Astrocytes diversify into superficial-, mid- and deep-layer subtypes distinct from neuronal laminae, yet instructed by neuronal cues.

    • Omer Ali Bayraktar
    • , Theresa Bartels
    • , Staffan Holmqvist
    • , Vitalii Kleshchevnikov
    • , Araks Martirosyan
    • , Damon Polioudakis
    • , Lucile Ben Haim
    • , Adam M. H. Young
    • , Mykhailo Y. Batiuk
    • , Kirti Prakash
    • , Alexander Brown
    • , Kenny Roberts
    • , Mercedes F. Paredes
    • , Riki Kawaguchi
    • , John H. Stockley
    • , Khalida Sabeur
    • , Sandra M. Chang
    • , Eric Huang
    • , Peter Hutchinson
    • , Erik M. Ullian
    • , Martin Hemberg
    • , Giovanni Coppola
    • , Matthew G. Holt
    • , Daniel H. Geschwind
    •  & David H. Rowitch
  • Article |

    Mohammad et al. show that prenatal alcohol exposure increases Kcnn2 activity in the mouse cerebral cortex. Blockade of Kcnn2 improves learning deficits in a mouse model of fetal alcohol spectrum disorders.

    • Shahid Mohammad
    • , Stephen J. Page
    • , Li Wang
    • , Seiji Ishii
    • , Peijun Li
    • , Toru Sasaki
    • , Aiesha Basha
    • , Anna Salzberg
    • , Zenaide Quezado
    • , Fumiaki Imamura
    • , Hirotaka Nishi
    • , Keiichi Isaka
    • , Joshua G. Corbin
    • , Judy S. Liu
    • , Yuka Imamura Kawasawa
    • , Masaaki Torii
    •  & Kazue Hashimoto-Torii
  • Technical Report |

    Sey et al. report a computational tool, H-MAGMA, that extracts neurobiological insights from brain-disorder GWAS by linking risk variants to their cognate genes using chromatin interaction profiles from human brain tissue.

    • Nancy Y. A. Sey
    • , Benxia Hu
    • , Won Mah
    • , Harper Fauni
    • , Jessica Caitlin McAfee
    • , Prashanth Rajarajan
    • , Kristen J. Brennand
    • , Schahram Akbarian
    •  & Hyejung Won
  • Article |

    Chen, Deister et al. show that Shank3B-knockout mice display hypersensitivity to tactile sensory stimulation and that dysfunction of interneurons in somatosensory cortex contributes to the sensory hyper-reactivity in this mouse model of autism.

    • Qian Chen
    • , Christopher A. Deister
    • , Xian Gao
    • , Baolin Guo
    • , Taylor Lynn-Jones
    • , Naiyan Chen
    • , Michael F. Wells
    • , Runpeng Liu
    • , Michael J. Goard
    • , Jordane Dimidschstein
    • , Shijing Feng
    • , Yiwu Shi
    • , Weiping Liao
    • , Zhonghua Lu
    • , Gord Fishell
    • , Christopher I. Moore
    •  & Guoping Feng
  • News & Views |

    Motor learning is composed of explicit ‘strategic’ components and implicit ‘automatic’ components. Miyamoto and colleagues reveal how these components work together during visuomotor adaptation, providing evidence that an implicit component corrects for a noisy explicit process.

    • Olivier Codol
    • , Giacomo Ariani
    •  & Jonathan A. Michaels
  • Article |

    Zhou et al. unveil a novel role for activated microglia and macrophages during wound healing after CNS injury. Microglia promote corralling and form a protective barrier at the injury penumbra via the axon guidance receptor Plexin-B2.

    • Xiang Zhou
    • , Shalaka Wahane
    • , Marie-Sophie Friedl
    • , Michael Kluge
    • , Caroline C. Friedel
    • , Kleopatra Avrampou
    • , Venetia Zachariou
    • , Lei Guo
    • , Bin Zhang
    • , Xijing He
    • , Roland H. Friedel
    •  & Hongyan Zou
  • News & Views |

    Three new studies show that activity-dependent formation of myelin contributes to memory consolidation and recall, possibly by increasing functional coupling between neuronal ensembles encoding experience.

    • R. Douglas Fields
    •  & Olena Bukalo