Browse Articles

  • Resource |

    The connectivity of a cortical region is instrumental to its function. The authors generated brain-wide maps of the afferent input to four distinct cell types in the mPFC to reveal the structural architecture that underlies the mPFC’s functions.

    • Sofie Ährlund-Richter
    • , Yang Xuan
    • , Josina Anna van Lunteren
    • , Hoseok Kim
    • , Cantin Ortiz
    • , Iskra Pollak Dorocic
    • , Konstantinos Meletis
    •  & Marie Carlén
  • Technical Report |

    A modified brain-organoid culture generates extensive axon outgrowth with specific tract-like patterns. Organoid tracts connect neurons across distant sites and can innervate and stimulate co-cultured mouse spinal cord tissue to elicit muscle contractions.

    • Stefano L. Giandomenico
    • , Susanna B. Mierau
    • , George M. Gibbons
    • , Lea M. D. Wenger
    • , Laura Masullo
    • , Timothy Sit
    • , Magdalena Sutcliffe
    • , Jerome Boulanger
    • , Marco Tripodi
    • , Emmanuel Derivery
    • , Ole Paulsen
    • , András Lakatos
    •  & Madeline A. Lancaster
  • 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
  • News & Views |

    Astrocytes are emerging as causal or modulating factors in diverse neurological disorders. Two papers published in Nature Neuroscience in 2007 revealed astrocytes as causally contributing to motor neuron loss in amyotrophic lateral sclerosis, thereby challenging the longstanding neuron-centric view of neurodegenerative disease.

    • Shane A. Liddelow
    •  & Michael V. Sofroniew
  • Brief Communication |

    Park et al. demonstrate in vivo the efficacy of Cas9 nanocomplexes as therapeutic agents in mouse models of Alzheimer’s disease. This strategy may be applicable to the treatment of a broad range of neurological diseases.

    • Hanseul Park
    • , Jungju Oh
    • , Gayong Shim
    • , Byounggook Cho
    • , Yujung Chang
    • , Siyoung Kim
    • , Soonbong Baek
    • , Hongwon Kim
    • , Jeain Shin
    • , Hwan Choi
    • , Junsang Yoo
    • , Junyeop Kim
    • , Won Jun
    • , Minhyung Lee
    • , Christopher J Lengner
    • , Yu-Kyoung Oh
    •  & Jongpil Kim
  • Resource |

    The lateral hypothalamic area (LHA) regulates fundamental aspects of innate behavior. However, the circuit-level underpinnings of LHA function are poorly understood given its cellular heterogeneity. Here, Mickelsen et al. employ a single-cell RNA-sequencing approach to classify molecularly distinct cell types in the mouse LHA.

    • Laura E. Mickelsen
    • , Mohan Bolisetty
    • , Brock R. Chimileski
    • , Akie Fujita
    • , Eric J. Beltrami
    • , James T. Costanzo
    • , Jacob R. Naparstek
    • , Paul Robson
    •  & Alexander C. Jackson
  • News & Views |

    In this issue of Nature Neuroscience, Kim and colleagues report that corticotropin-releasing factor neurons in the paraventricular nucleus, known essential regulators of the neuroendocrine axis, encode the valence of environmental stimuli through a bidirectional strategy and modulate animals’ immediate behavioral responses.

    • Rui Lin
    • , Ting Yan
    •  & Minmin Luo
  • Article |

    Animals must determine quickly whether any given environmental stimuli are beneficial or detrimental. This work reveals a novel strategy to encode opposing valences by a single population of CRF neurons in the hypothalamus.

    • Jineun Kim
    • , Seongju Lee
    • , Yi-Ya Fang
    • , Anna Shin
    • , Seahyung Park
    • , Koichi Hashikawa
    • , Shreelatha Bhat
    • , Daesoo Kim
    • , Jong-Woo Sohn
    • , Dayu Lin
    •  & Greg S. B. Suh
  • Article |

    A simple behavioral task identifies two qualitatively different groups within the general population, according to their speech-to-speech synchronization abilities. Group pertinence predicts brain function and anatomy, as well as word-learning performance.

    • M. Florencia Assaneo
    • , Pablo Ripollés
    • , Joan Orpella
    • , Wy Ming Lin
    • , Ruth de Diego-Balaguer
    •  & David Poeppel
  • Article |

    Miller et al. show that subpopulations of D1 receptor-expressing neurons in the medial amygdala modulate approach–avoidance responses to threats through inhibitory and excitatory projections to the extended amygdala and hypothalamus, respectively.

    • Samara M. Miller
    • , Daniele Marcotulli
    • , Angela Shen
    •  & Larry S. Zweifel
  • Review Article |

    Considerations of optimality have served perceptual neuroscience well, but accumulating evidence suggests that optimal goals can be achieved by heuristic means. Theory that embraces this is key to uncovering the neural basis of perceptual behavior.

    • Justin L. Gardner
  • Article |

    Causal manipulations combined with simultaneous recordings of both interneurons and medium spiny neurons in the striatum reveal dissociable contributions of cholinergic and parvalbumin interneurons in movement initiation and termination.

    • Howard J. Gritton
    • , William M. Howe
    • , Michael F. Romano
    • , Alexandra G. DiFeliceantonio
    • , Mark A. Kramer
    • , Venkatesh Saligrama
    • , Mark E. Bucklin
    • , Dana Zemel
    •  & Xue Han
  • News & Views |

    Disproportionate reactions to unexpected stimuli and greater attention to perceived threat are cardinal symptoms of post-traumatic stress disorder. Computational psychiatry helps explain how these responses develop and result from abnormalities in learning and prediction during and after traumatic events.

    • Peggy Seriès
  • News & Views |

    Excessive synapse elimination during adolescence and early adulthood has long been hypothesized to underpin the emergence of schizophrenia. A new study reports that induced microglia-like cells derived from schizophrenia patients display increased synapse engulfment, which may be partly mediated by a genetic schizophrenia-risk variant.

    • Meiyan Wang
    • , Lei Zhang
    •  & Fred H. Gage
  • News & Views |

    Geneticists are pushing for ever-greater sample sizes to gain insight into the genetic variation that contributes to psychiatric disorders. Two new genome-wide association studies leverage this approach to provide broad, population-level perspectives on the genetic basis for major depressive disorder and the shared genetic risk that underlies multiple disorders.

    • Lea Karatheodoris Davis
  • Article |

    The cellular origin of glioblastoma is controversial. Alcantara Llaguno et al. examine the tumor-initiating capacity of adult neuronal cells and find that increasing lineage commitment is accompanied by decreasing susceptibility to transformation.

    • Sheila Alcantara Llaguno
    • , Daochun Sun
    • , Alicia M. Pedraza
    • , Elsa Vera
    • , Zilai Wang
    • , Dennis K. Burns
    •  & Luis F. Parada
  • Article |

    Li et al. have discovered a necessary role for the DNA modification N6-methyldeoxyadenosine (m6dA) in regulating experience-dependent gene expression and the formation of fear extinction memory. These findings expand the scope of DNA modifications in the adult brain.

    • Xiang Li
    • , Qiongyi Zhao
    • , Wei Wei
    • , Quan Lin
    • , Christophe Magnan
    • , Michael R. Emami
    • , Luis E. Wearick-Silva
    • , Thiago W. Viola
    • , Paul R. Marshall
    • , Jiayu Yin
    • , Sachithrani U. Madugalle
    • , Ziqi Wang
    • , Sarah Nainar
    • , Cathrine Broberg Vågbø
    • , Laura J. Leighton
    • , Esmi L. Zajaczkowski
    • , Ke Ke
    • , Rodrigo Grassi-Oliveira
    • , Magnar Bjørås
    • , Pierre F. Baldi
    • , Robert C. Spitale
    •  & Timothy W. Bredy
  • Article |

    The authors report that mitophagy is impaired in Alzheimer’s disease. Stimulation of mitophagy reverses cognitive deficits in nematode and mouse models of Alzheimer’s disease, suggesting a potential therapeutic intervention.

    • Evandro F. Fang
    • , Yujun Hou
    • , Konstantinos Palikaras
    • , Bryan A. Adriaanse
    • , Jesse S. Kerr
    • , Beimeng Yang
    • , Sofie Lautrup
    • , Md Mahdi Hasan-Olive
    • , Domenica Caponio
    • , Xiuli Dan
    • , Paula Rocktäschel
    • , Deborah L. Croteau
    • , Mansour Akbari
    • , Nigel H. Greig
    • , Tormod Fladby
    • , Hilde Nilsen
    • , M. Zameel Cader
    • , Mark P. Mattson
    • , Nektarios Tavernarakis
    •  & Vilhelm A. Bohr
  • Article |

    Shen et al. show that FMRP promotes mitochondrial fusion through HTT. FMRP loss caused fragmented mitochondria and oxidative stress in immature neurons, and enhancing mitochondrial fusion rescued neuronal and behavioral deficits in Fmr1-mutant mice.

    • Minjie Shen
    • , Feifei Wang
    • , Meng Li
    • , Nirnath Sah
    • , Michael E. Stockton
    • , Joseph J. Tidei
    • , Yu Gao
    • , Tomer Korabelnikov
    • , Sudharsan Kannan
    • , Jason D. Vevea
    • , Edwin R. Chapman
    • , Anita Bhattacharyya
    • , Henriette van Praag
    •  & Xinyu Zhao
  • Brief Communication |

    Weiler et al demonstrate that the fastest spinal feedback pathway can integrate information from the elbow and wrist, and take into account the arm’s orientation to produce corrective responses that help to maintain the hand’s position in space.

    • Jeffrey Weiler
    • , Paul L. Gribble
    •  & J. Andrew Pruszynski
  • Article |

    The authors found that white blood cells plug about 2% of capillaries in the brains of Alzheimer’s disease mouse models. When the adhesion of these cells was blocked, cerebral blood flow immediately increased and cognitive performance rapidly improved.

    • Jean C. Cruz Hernández
    • , Oliver Bracko
    • , Calvin J. Kersbergen
    • , Victorine Muse
    • , Mohammad Haft-Javaherian
    • , Maxime Berg
    • , Laibaik Park
    • , Lindsay K. Vinarcsik
    • , Iryna Ivasyk
    • , Daniel A. Rivera
    • , Yiming Kang
    • , Marta Cortes-Canteli
    • , Myriam Peyrounette
    • , Vincent Doyeux
    • , Amy Smith
    • , Joan Zhou
    • , Gabriel Otte
    • , Jeffrey D. Beverly
    • , Elizabeth Davenport
    • , Yohan Davit
    • , Charles P. Lin
    • , Sidney Strickland
    • , Costantino Iadecola
    • , Sylvie Lorthois
    • , Nozomi Nishimura
    •  & Chris B. Schaffer
  • News & Views |

    Variability is a ubiquitous aspect of neural recordings. In an influential paper, Churchland et al. (2010) compiled data from many cortical areas to demonstrate that variability generally decreases upon presentation of a stimulus. What are the implications of this finding?

    • Adrienne L. Fairhall
  • Article |

    Postmortem studies indicate reduced synaptic density in schizophrenia. Sellgren et al. show increased synaptic pruning in patient-derived cell models and provide evidence that C4 risk variants increase engulfment, while minocycline decreases it.

    • Carl M. Sellgren
    • , Jessica Gracias
    • , Bradley Watmuff
    • , Jonathan D. Biag
    • , Jessica M. Thanos
    • , Paul B. Whittredge
    • , Ting Fu
    • , Kathleen Worringer
    • , Hannah E. Brown
    • , Jennifer Wang
    • , Ajamete Kaykas
    • , Rakesh Karmacharya
    • , Carleton P. Goold
    • , Steven D. Sheridan
    •  & Roy H. Perlis
  • Article |

    An interaction between UTX and 53BP1, which occurs in humans but not mice, promotes neurogenic gene expression that underlies neuronal differentiation and cortical development, perhaps providing insight into human-specific neurodevelopment.

    • Xiaoyang Yang
    • , Beisi Xu
    • , Brett Mulvey
    • , Myron Evans
    • , Samuel Jordan
    • , Yong-Dong Wang
    • , Vishwajeeth Pagala
    • , Junmin Peng
    • , Yiping Fan
    • , Arishna Patel
    •  & Jamy C. Peng
  • Article |

    van Ede et al. show that both sensory qualities and motor responses associated with information held in mind are accessed simultaneously to guide behavior. The findings help bridge the fields of visual working memory and action planning.

    • Freek van Ede
    • , Sammi R. Chekroud
    • , Mark G. Stokes
    •  & Anna C. Nobre
  • Article |

    The authors conducted a genetic meta-analysis of depression and found 269 associated genes. These genes highlight several potential drug repositioning opportunities, and relationships with depression were found for neuroticism and smoking.

    • David M. Howard
    • , Mark J. Adams
    • , Toni-Kim Clarke
    • , Jonathan D. Hafferty
    • , Jude Gibson
    • , Masoud Shirali
    • , Jonathan R. I. Coleman
    • , Saskia P. Hagenaars
    • , Joey Ward
    • , Eleanor M. Wigmore
    • , Clara Alloza
    • , Xueyi Shen
    • , Miruna C. Barbu
    • , Eileen Y. Xu
    • , Heather C. Whalley
    • , Riccardo E. Marioni
    • , David J. Porteous
    • , Gail Davies
    • , Ian J. Deary
    • , Gibran Hemani
    • , Klaus Berger
    • , Henning Teismann
    • , Rajesh Rawal
    • , Volker Arolt
    • , Bernhard T. Baune
    • , Udo Dannlowski
    • , Katharina Domschke
    • , Chao Tian
    • , David A. Hinds
    • , Maciej Trzaskowski
    • , Enda M. Byrne
    • , Stephan Ripke
    • , Daniel J. Smith
    • , Patrick F. Sullivan
    • , Naomi R. Wray
    • , Gerome Breen
    • , Cathryn M. Lewis
    •  & Andrew M. McIntosh
  • Article |

    Besnard et al. uncover functional heterogeneity of somatostatin interneurons (SST-INs) in the dorsolateral septum and reveal a role for a subpopulation of SST-INs as hippocampal relays that govern mobility to calibrate adaptive fear responses.

    • Antoine Besnard
    • , Yuan Gao
    • , Michael TaeWoo Kim
    • , Hannah Twarkowski
    • , Alexander Keith Reed
    • , Tomer Langberg
    • , Wendy Feng
    • , Xiangmin Xu
    • , Dieter Saur
    • , Larry S. Zweifel
    • , Ian Davison
    •  & Amar Sahay
  • Article |

    DeNardo et al. characterize TRAP2, which allows genetic access to neurons based on their activity, and use it to show that neuronal ensembles in prelimbic cortex for remote fear memory undergo dynamic changes during the first 14 days after learning.

    • Laura A. DeNardo
    • , Cindy D. Liu
    • , William E. Allen
    • , Eliza L. Adams
    • , Drew Friedmann
    • , Lisa Fu
    • , Casey J. Guenthner
    • , Marc Tessier-Lavigne
    •  & Liqun Luo
  • Technical Report |

    The authors generate 3D brain organoids containing oligodendrocytes, astrocytes, and neurons derived from human pluripotent stem cells. These human oligodendrocytes are transcriptionally similar to primary cells and mature to myelinate axons.

    • Rebecca M. Marton
    • , Yuki Miura
    • , Steven A. Sloan
    • , Qingyun Li
    • , Omer Revah
    • , Rebecca J. Levy
    • , John R. Huguenard
    •  & Sergiu P. Pașca
  • Technical Report |

    Inhibitory interneurons shape neuronal activity of cortical principal neurons. Yetman et al. developed a genetic strategy to elucidate the organization of inhibitory neuron subtypes sending inputs to principal neurons.

    • Michael J. Yetman
    • , Eric Washburn
    • , Jung Ho Hyun
    • , Fumitaka Osakada
    • , Yasufumi Hayano
    • , Hongkui Zeng
    • , Edward M. Callaway
    • , Hyung-Bae Kwon
    •  & Hiroki Taniguchi
  • Article |

    Schork et al. identify novel variants contributing to shared risk among psychiatric disorders and suggest that these variants act through the disruption of early neurodevelopment.

    • Andrew J. Schork
    • , Hyejung Won
    • , Vivek Appadurai
    • , Ron Nudel
    • , Mike Gandal
    • , Olivier Delaneau
    • , Malene Revsbech Christiansen
    • , David M. Hougaard
    • , Marie Bækved-Hansen
    • , Jonas Bybjerg-Grauholm
    • , Marianne Giørtz Pedersen
    • , Esben Agerbo
    • , Carsten Bøcker Pedersen
    • , Benjamin M. Neale
    • , Mark J. Daly
    • , Naomi R. Wray
    • , Merete Nordentoft
    • , Ole Mors
    • , Anders D. Børglum
    • , Preben Bo Mortensen
    • , Alfonso Buil
    • , Wesley K. Thompson
    • , Daniel H. Geschwind
    •  & Thomas Werge
  • Article |

    Neuronal responses in a higher-order auditory cortical area reveal striking attention-driven effects, long-term learning, and stimulus–action coupling, indicating a dynamic intermediate stage between sensory and frontal cortex representations.

    • Diego Elgueda
    • , Daniel Duque
    • , Susanne Radtke-Schuller
    • , Pingbo Yin
    • , Stephen V. David
    • , Shihab A. Shamma
    •  & Jonathan B. Fritz
  • 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 |

    PTSD symptom severity in combat veterans was associated with enhanced sensitivity to prediction errors and lower neural tracking of value and learning rate, providing evidence for neurocomputational contributions to trauma-related psychopathology.

    • Philipp Homan
    • , Ifat Levy
    • , Eric Feltham
    • , Charles Gordon
    • , Jingchu Hu
    • , Jian Li
    • , Robert H. Pietrzak
    • , Steven Southwick
    • , John H. Krystal
    • , Ilan Harpaz-Rotem
    •  & Daniela Schiller
  • 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 |

    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 |

    Blood vessels help macrophage entry. Zhou et al. show that activated microvessels serve as critical portals for macrophage entry to boost inflammation after spinal cord injury.

    • Tian Zhou
    • , Yiming Zheng
    • , Li Sun
    • , Smaranda Ruxandra Badea
    • , Yuanhu Jin
    • , Yang Liu
    • , Alyssa J. Rolfe
    • , Haitao Sun
    • , Xi Wang
    • , Zhijian Cheng
    • , Zhaoshuai Huang
    • , Na Zhao
    • , Xin Sun
    • , Jinhua Li
    • , Jianqing Fan
    • , Choogon Lee
    • , Timothy L. Megraw
    • , Wutian Wu
    • , Guixue Wang
    •  & Yi Ren
  • 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 |

    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
  • 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