Neuroscience

  • Article
    | Open Access

    In the cerebral cortex, information is processed by multiple hierarchically organized areas, reciprocally connected via feedforward and feedback circuits. Here the authors show that in primate visual cortex, feedforward projection neurons receive monosynaptic feedback contacts selectively from the area to which they project.

    • Caitlin Siu
    • , Justin Balsor
    •  & Alessandra Angelucci
  • Article
    | Open Access

    The relationship between the human structural and functional connectome is still not well established. Here the authors show the interindividual variability that exists in regional coupling of structural and functional connectivity across the brain, and that this is heritable.

    • Zijin Gu
    • , Keith Wakefield Jamison
    •  & Amy Kuceyeski
  • Article
    | Open Access

    The mechanisms stimulating adult neurogenesis are unclear. Here, the authors show the contribution of cholinergic and GABAergic signalling within the locomotor network to spinal cord neurogenesis during homeostasis and regeneration, showing neurogenesis depends on circuit activity in the adult zebrafish.

    • Weipang Chang
    • , Andrea Pedroni
    •  & Konstantinos Ampatzis
  • Article
    | Open Access

    Mapping neuronal proteomes with genetic, subcellular, and temporal specificity is a challenging task. This study uncovers proteome dynamics in two classes of striatal spiny projection neurons in the mouse brain using a genetically targeted APEX2-based proximity labeling approach.

    • V. Dumrongprechachan
    • , R. B. Salisbury
    •  & Y. Kozorovitskiy
  • Article
    | Open Access

    When two memories are similar, their encoding and retrieval can be disrupted by each other. Here the authors show that memory interference is resolved through abrupt remapping of activity patterns in the human hippocampal CA3 and dentate gyrus.

    • Guo Wanjia
    • , Serra E. Favila
    •  & Brice A. Kuhl
  • Article
    | Open Access

    Hippocampal pyramidal cells encode an animal’s location by single action potentials and complex spike bursts. The authors show that Kcnq3-containing M-channels synergistically with GABAergic inputs coordinate complex spike bursts during theta oscillations, which is a key mechanism for spatial coding by single spikes.

    • Xiaojie Gao
    • , Franziska Bender
    •  & Alexey Ponomarenko
  • Article
    | Open Access

    Previous work has shown that in rodents phase precession – the phase of action potentials relative to the theta oscillation – is associated with the representation of sequential locations. Here the authors demonstrate that phase precession also occurs in the human hippocampus using single neuron and LFP recordings.

    • Leila Reddy
    • , Matthew W. Self
    •  & Pieter R. Roelfsema
  • Article
    | Open Access

    NEK1 mutations promote lethality early in life and ALS late in life via unknown mechanisms. Here, the authors show that NEK1 mutation disrupts retromer-mediated trafficking and promotes RIPK1 activation, connecting retromer trafficking and metabolism to neuroinflammation by dietary intervention.

    • Huibing Wang
    • , Weiwei Qi
    •  & Junying Yuan
  • Article
    | Open Access

    Engineering de novo synapse-like connections between neurons could enhance our understanding of neuronal circuits and how they generate behaviour. The authors present a two-component system that creates synthetic neuromodulatory connections to manipulate intracellular Ca2+ levels in in vivo neural circuits.

    • Josh D. Hawk
    • , Elias M. Wisdom
    •  & Daniel A. Colón-Ramos
  • Article
    | Open Access

    Myelination patterns of different neurons in grey matter have not been fully defined. Here, the authors show that axon diameter and neuronal identity influence myelination patterns in the intact mouse somatosensory cortex. In vivo imaging revealed that remyelination altered myelin patterns but restored overall myelin content on distinct neuron subtypes.

    • Cody L. Call
    •  & Dwight E. Bergles
  • Article
    | Open Access

    Organoids have improved disease modeling. Here, the authors generate human sensorimotor organoids derived from hiPSCs of individuals with ALS. These organoids contain skeletal muscle, sensory and motor neurons as well as astrocytes, microglia, and vasculature and form neuromuscular junctions.

    • João D. Pereira
    • , Daniel M. DuBreuil
    •  & Brian J. Wainger
  • Article
    | Open Access

    Glucocorticoid hormones (GCs) are of critical importance for maintaining brain health, but their involvement in mental disorders is poorly understood. Here the authors show how GCs act through hippocampal mineralocorticoid and glucocorticoid receptors to impact the gene regulatory programs underpinning neuronal plasticity, ciliogenesis and behavioral adaptation.

    • Karen R. Mifsud
    • , Clare L. M. Kennedy
    •  & Johannes M. H. M. Reul
  • Article
    | Open Access

    The relative roles of visual, parietal, and frontal cortex in working memory have been actively debated. Here, the authors show that distraction impacts visual working memory representations in primary visual areas, indicating that these regions play a key role in the maintenance of working memory.

    • Grace E. Hallenbeck
    • , Thomas C. Sprague
    •  & Clayton E. Curtis
  • Article
    | Open Access

    NMDA receptors are glutamate-gated ion channels essential for synapse maturation and plasticity. Here the authors show that GluN2A and GluN2B NMDA receptors — the two principal subtypes NMDARs in the adult CNS — operate through distinct long range allosteric mechanisms.

    • Meilin Tian
    • , David Stroebel
    •  & Pierre Paoletti
  • Article
    | Open Access

    Making a decision requires one to differentiate between choice options, committing to one and leaving the other behind. Here, the authors show that decision-making paradoxically binds options together, such that the outcome of the choice ends up changing the value of both the chosen and the unchosen options, in opposite directions.

    • Natalie Biderman
    •  & Daphna Shohamy
  • Article
    | Open Access

    Glucocorticoids are associated with stress. Here, the authors show that high levels of glucocorticoid stress promote secretory autophagy of matrix metalloproteinase 9 via a stress responsive chaperone, increasing brain-derived neurotrophic factor processing and potentially altering adult synaptic plasticity.

    • Silvia Martinelli
    • , Elmira A. Anderzhanova
    •  & Nils C. Gassen
  • Article
    | Open Access

    Here, the authors show that microglia depletion results in unstable wakefulness and altered levels of ceramide, influencing microglia in the mouse thalamic reticular nucleus (TRN). Stable wakefulness can be restored by activation of the TRN or inhibition of ceramide production in the mouse brain.

    • Hanxiao Liu
    • , Xinxing Wang
    •  & Qiaojie Xiong
  • Article
    | Open Access

    Visceral adiposity is a risk factor for cognitive decline, but subcutaneous adipose tissue (SAT) is not and may be protective. Here, the authors show that beige adipocytes are indispensable for the neuroprotective effects of SAT. Beige fat knockout mice were more susceptible to the neuroimmune and cognitive effects of obesity, and in normal mice, SAT transplants protected against chronic obesity via beige fat-dependent mechanisms.

    • De-Huang Guo
    • , Masaki Yamamoto
    •  & Alexis M. Stranahan
  • 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