Neuroscience

  • Article
    | Open Access

    Visual processing necessitates both extracting and discarding information. Here, the authors use a specialized set of stimuli and two complementary discrimination tasks to demonstrate the opposing perceptual implications of these two aspects of information processing.

    • Corey M. Ziemba
    •  & Eero P. Simoncelli
  • Article
    | Open Access

    The willingness to exert effort into demanding tasks often declines over time through fatigue. Here the authors provide a computational account of the moment-to-moment dynamics of fatigue and its impact on effort-based choices, and reveal the neural mechanisms that underlie such computations.

    • Tanja Müller
    • , Miriam C. Klein-Flügge
    •  & Matthew A. J. Apps
  • Article
    | Open Access

    Chronic use of mTORC1 inhibitors produces undesirable side effects in humans which limit their value for CNS disorders treatment. The authors present a binary drug strategy to protects mTORC1 activity in the periphery and show its potential utility in preclinical models of alcohol use disorder.

    • Yann Ehinger
    • , Ziyang Zhang
    •  & Dorit Ron
  • Article
    | Open Access

    There is an unmet clinical need to develop therapies to alleviate metastatic bone pain, frequently observed in patients with advanced cancers. Here, using mouse models of bone cancer pain, the authors show that STING agonists not only suppress bone cancer tumor burden, but also attenuate bone pain and reduce cancer-induced bone destruction.

    • Kaiyuan Wang
    • , Christopher R. Donnelly
    •  & Ru-Rong Ji
  • Article
    | Open Access

    Currently, bidirectional control of activity in the same neurons in the same experiment is difficult. Here the authors report a Bidirectional Pair of Opsins for Light-induced Excitation and Silencing, BiPOLES, which they use in a range of organisms including worms, fruit flies, mice and ferrets.

    • Johannes Vierock
    • , Silvia Rodriguez-Rozada
    •  & J. Simon Wiegert
  • Article
    | Open Access

    Microbial rhodopsins can be used to control action potentials, while animal opsins can be used to control intracellular signaling pathways. The authors identify Opn7b as constitutively active Gi/o coupled receptor that can be deactivated by light and used to modulate neuronal activity.

    • Raziye Karapinar
    • , Jan Claudius Schwitalla
    •  & Stefan Herlitze
  • Article
    | Open Access

    Multi-sensory input can lead to dendritic integration at the single neuron level. Here the authors show that combined auditory and somatosensory input increases distal dendritic and somatic activity in layer 2/3 pyramidal neurons of the primary somatosensory cortex and decreases response latency during somatosensory-based goal-directed behaviour.

    • L. Godenzini
    • , D. Alwis
    •  & L. M. Palmer
  • Article
    | Open Access

    In neurons and other cells, contacts between organelles regulates function and subcellular organization, but the precise mechanisms and effects are unclear. Here the authors show that endoplasmic reticulum (ER) tubules in the soma of neurons regulate lysosome localization and function by regulating lysosomal fission, suggesting a role for ER – lysosome inter-organelle membrane contact sites in lysosomal axonal availability.

    • Nazmiye Özkan
    • , Max Koppers
    •  & Ginny G. Farías
  • Article
    | Open Access

    Feedback modulates visual neurons, thought to help achieve flexible task performance. Here, the authors show decision-related feedback is not only relayed to task-relevant neurons, suggesting a broader mechanism and supporting a previously hypothesized link to feature-based attention.

    • Katrina R. Quinn
    • , Lenka Seillier
    •  & Hendrikje Nienborg
  • Article
    | Open Access

    Scintillators emit visible luminescence when irradiated with X-rays and may enable remote optogenetic control of neurons deep in the brain. The authors inject an inorganic scintillator to activate and inhibit midbrain dopamine neurons in freely moving mice by X-ray irradiation to modulate place preference behavior.

    • Takanori Matsubara
    • , Takayuki Yanagida
    •  & Takayuki Yamashita
  • Article
    | Open Access

    People can search for memories based on their content or context, defined as when and where they were formed. Here, the authors use direct brain recordings to provide evidence in line with the idea that separable neural systems retrieve these two types of information and predict whether recall is organized by time or content.

    • James E. Kragel
    • , Youssef Ezzyat
    •  & Michael J. Kahana
  • Article
    | Open Access

    Intratelencephalic and pyramidal tract neurons are two major types of cortical excitatory neurons that project to cortical and subcortical structures. The authors show that in the prefrontal cortex the two populations have different roles for the maintenance of working memory and for tracking the passage of time.

    • Jung Won Bae
    • , Huijeong Jeong
    •  & Min Whan Jung
  • Article
    | Open Access

    Astrocytes have functions crucial for brain homeostasis, which are disrupted in many neurological disorders, but how these functions are established during astrocyte maturation is largely unknown. Here the authors show transcriptional and chromatin changes underlying astrocyte maturation in mice and identify transcription factors regulating maturation of cultured astrocytes.

    • Michael Lattke
    • , Robert Goldstone
    •  & Francois Guillemot
  • Article
    | Open Access

    Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in neurofibromin and associated with disruptions in physiology and behavior. Here the authors show that neurofibromin regulates metabolic homeostasis via a discrete brain circuit in a Drosophila model of NF1.

    • Valentina Botero
    • , Bethany A. Stanhope
    •  & Seth M. Tomchik
  • Article
    | Open Access

    How genes sculpt the complex architecture of the human connectome remains unclear. Here, the authors show that genes preferentially influence the strength of connectivity between functionally valuable, metabolically costly connections between brain network hubs.

    • Aurina Arnatkeviciute
    • , Ben D. Fulcher
    •  & Alex Fornito
  • Article
    | Open Access

    The formation of large-scale brain networks represents crucial developmental processes that can drive individual differences in cognition and which are associated with multiple neurodevelopmental conditions. Here, the authors use generative network modelling to provide a computational framework for understanding neurodevelopmental diversity.

    • Danyal Akarca
    • , Petra E. Vértes
    •  & Duncan E. Astle
  • Article
    | Open Access

    The authors present a method for the conversion of full-length tau protein into seeding-competent amyloid fibrils without heparin or other negatively charged co-factors, which could be useful for studying the effects of post-translational modifications on Tau aggregation as well as to identify potential inhibitors of tau aggregation. Biochemical experiments and solid-state NMR spectroscopy measurements show that these co-factor-free tau fibrils have similar properties as amyloid fibrils isolated from brain tissue but differ from those of commonly used heparin-induced tau fibrils.

    • Pijush Chakraborty
    • , Gwladys Rivière
    •  & Markus Zweckstetter
  • Article
    | Open Access

    Prokineticin-2 (Prok2) is a secreted protein involved in many physiological processes. Here, the authors show that Prok2 prevents neuronal cell ferroptosis after traumatic brain injury and its administration before cortical injury reduces neuronal degeneration, and motor and cognitive impairments.

    • Zhongyuan Bao
    • , Yinlong Liu
    •  & Jing Ji
  • Article
    | Open Access

    Recurrent spiking neural networks have garnered interest due to their energy efficiency; however, they suffer from lower accuracy compared to conventional neural networks. Here, the authors present an alternative neuron model and its efficient hardware implementation, demonstrating high classification accuracy across a range of datasets.

    • Ahmed Shaban
    • , Sai Sukruth Bezugam
    •  & Manan Suri
  • Article
    | Open Access

    Sleep is known to promote memory consolidation, but the extent to which this is dependent on the memory’s relevance remains unclear. Here, the authors use a brain decoding approach to show that neural representations of rewarded experiences undergo a privileged reactivation during sleep, favouring their consolidation.

    • Virginie Sterpenich
    • , Mojca K. M. van Schie
    •  & Sophie Schwartz
  • Article
    | Open Access

    The central amygdala inhibitory microcircuits mediate fear extinction by reversible, stimulus- and context-specific changes in neuronal responses. These alterations are absent when extinction is deficient and selective silencing of PKCδ neurons impairs fear extinction.

    • Nigel Whittle
    • , Jonathan Fadok
    •  & Stéphane Ciocchi
  • Article
    | Open Access

    Despite the profound knowledge of sex pheromones, little is known about the coevolutionary mechanisms and constraints on their production and detection. Whole-genome sequences from 99 drosophilids, with chemical and behavioural data, show that sex pheromones and their cognate olfactory channels evolve rapidly and independently.

    • Mohammed A. Khallaf
    • , Rongfeng Cui
    •  & Markus Knaden
  • Article
    | Open Access

    Axonal swellings have been found on Purkinje cell axons in the cerebellum both during development and disease. The authors show that axons with swellings propagate action potentials with higher fidelity than those without and that mice with more axonal swellings learn cerebellar-related tasks better.

    • Daneck Lang-Ouellette
    • , Kim M. Gruver
    •  & Alanna J. Watt
  • Article
    | Open Access

    Limited understanding of the interactions between nanoparticle drug carriers and the blood-brain barrier underlies many translational failures in treatments of brain disorders. Here the authors use two-photon microscopy in mice to characterize the receptor-mediated transcytosis of nanoparticles at all steps of delivery from the blood to the brain in vivo.

    • Krzysztof Kucharz
    • , Kasper Kristensen
    •  & Martin Johannes Lauritzen
  • Article
    | Open Access

    α-ketoglutarate (αKG) is an intermediate in the tricarboxylic acid cycle that is required in the nucleus for genomic DNA demethylation by Tet3. Here, the authors show that the enzyme glutamate dehydrogenase, which converts glutamate to αKG, is redirected from the mitochondria to the nucleus.

    • Franziska R. Traube
    • , Dilara Özdemir
    •  & Thomas Carell
  • Article
    | Open Access

    Ataxia Telangiectasia and Rad3-related (ATR) is a key regulator of replication stress response; yet, mutations within the ATR gene cause human ATR-Seckel Syndrome associated with microcephaly and intellectual disability. Here, the authors show neuron-specific ATR deletion increases intrinsic neuronal and epileptiform activity, revealing a function of ATR beyond its role in DNA damage response.

    • Murat Kirtay
    • , Josefine Sell
    •  & Zhao-Qi Wang
  • Article
    | Open Access

    Long noncoding RNAs (lncRNAs) are known to regulate the DNA damage response (DDR), however their role in the brain is less well studied. Here, the authors demonstrate a neuron-specific role for Brain Specific DNA-damage Related lncRNA1 (BS-DRL1) and show BS-DRL1 modulates DDR by interacting with HMGB1 in a cell-type specific manner.

    • Min-Min Lou
    • , Xiao-Qiang Tang
    •  & Wen-Yuan Wang
  • Article
    | Open Access

    Schinzel-Giedion syndrome (SGS) is a fatal developmental syndrome characterized by severe intellectual and physical deficits due, at least in part, to early neurodegeneration. Here the authors introduce a human SGS model that displays disease-relevant phenotypes to demonstrate that neuronal death in SGS originates from developmental alterations mainly in safeguarding cell identity and homeostasis.

    • Federica Banfi
    • , Alicia Rubio
    •  & Alessandro Sessa
  • Article
    | Open Access

    Attentional lapses occur in many forms such as mind-wandering or mindblanking. Here the authors show different types of attentional lapse are accompanied by slow waves, neural activity that is characteristic of transitions into sleep.

    • Thomas Andrillon
    • , Angus Burns
    •  & Naotsugu Tsuchiya
  • Article
    | Open Access

    The representation of space in mouse visual cortex was considered to be relatively uniform. The authors show that mice have improved visual resolution in a cortical region representing a location in space directly in front and slightly above them, showing that the representation of space in mouse visual cortex is non-uniform.

    • Enny H. van Beest
    • , Sreedeep Mukherjee
    •  & Matthew W. Self
  • Article
    | Open Access

    Working memory is a foundational component of cognition, but its mechanisms are poorly understood. Using a large sample of participants, this study identifies asymmetric dynamic interactions in cognitive control circuits, and their load-dependent network properties including controllability.

    • Weidong Cai
    • , Srikanth Ryali
    •  & Vinod Menon
  • Article
    | Open Access

    Synaptic inputs on neuronal dendrites exhibit remarkable organization at different spatial scales, which emerges during the early postnatal development. Kirchner and Gjorgjieva propose a biophysically motivated computational model to explain the different types of organization in mouse and ferret.

    • Jan H. Kirchner
    •  & Julijana Gjorgjieva
  • Article
    | Open Access

    The superior colliculus (SC) receives diverse cortical inputs to drive many behaviors. Here, based on comprehensive mapping of cortico-tectal projections, the authors refined the superior colliculus into medial, centromedial, centrolateral, and lateral zones, and characterized the input-output connectivity and morphology of neurons in each zone that serve the role of SC in goal-directed behaviors.

    • Nora L. Benavidez
    • , Michael S. Bienkowski
    •  & Hong-Wei Dong
  • Article
    | Open Access

    Definitive evidence for functional remapping after stroke remains lacking. Here, the authors performed in vivo intrinsic signal imaging and two-photon calcium imaging of sensory-evoked responses before and after photothrombotic stroke and found no evidence of remapping of lost functionalities to new circuits in peri-infarct cortex.

    • William A. Zeiger
    • , Máté Marosi
    •  & Carlos Portera-Cailliau
  • Article
    | Open Access

    The cellular heterogeneity in brain obscures the identification of robust cellular regulatory networks. Here the authors integrate genome-wide chromosome conformation data from sorted neurons and glia, with transcriptomic and enhancer profiles, to characterize cell-type-specific gene regulatory landscapes in the human brain, and provide insights into cell-type-specific gene regulatory networks in brain disorders.

    • Benxia Hu
    • , Hyejung Won
    •  & Daniel H. Geschwind
  • Article
    | Open Access

    In the primary auditory cortex, visual or tactile stimuli can modulate acoustically-driven activity. Here, the authors show that circuits linking the primary somatosensory cortex to both the auditory midbrain and thalamus allow tactile inputs to modulate auditory thalamocortical processing.

    • Michael Lohse
    • , Johannes C. Dahmen
    •  & Andrew J. King