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| Open AccessDisease related changes in ATAC-seq of iPSC-derived motor neuron lines from ALS patients and controls
Amyotrophic Lateral Sclerosis (ALS) is highly heritable but the mechanisms of sporadic ALS are not fully understood. In this study, the authors identify drivers of variation and disease-relevant changes in the epigenomic profile of iPSC-derived motor neuron lines generated from ALS patients and healthy controls as part of the Answer ALS program.
- Stanislav Tsitkov
- , Kelsey Valentine
- & Ernest Fraenkel
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Article
| Open AccessEye movements track prioritized auditory features in selective attention to natural speech
Anatomical overlap of respective brain regions suggests a joint network for attention and eye movements. Here, the authors show that gaze aligns with the acoustics of attended natural speech and differentiates between a target and a distractor in a cocktail party scenario.
- Quirin Gehmacher
- , Juliane Schubert
- & Nathan Weisz
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Article
| Open AccessCerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases
CSF biomarker concentrations may be influenced by non-disease related interindividual variability. Here, the authors show that reference proteins can capture this variability and enhance the accuracy of Alzheimer’s disease biomarkers.
- Linda Karlsson
- , Jacob Vogel
- & Oskar Hansson
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Article
| Open AccessLarge-language models facilitate discovery of the molecular signatures regulating sleep and activity
The knowledge in the large language model (LLM), generative pre-trained transformer (GPT) 3.5, is elicited to facilitate the discovery of MRE11 in regulating sleep in the presence of conspecifics by a multi-object video tracking system.
- Di Peng
- , Liubin Zheng
- & Luoying Zhang
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| Open AccessA role for nNOS in mediating stress and female sexual behavior in mice
Developmental stress can detrimentally affect adult female reproductive behavior, influencing sexual receptivity and fertility. Recent work has demonstrated neuronal nitric oxide (NO) synthase (nNOS)-promoted NO release in the ventromedial hypothalamus as a nexus between pre-pubertal stress and adult sexual behavior in mice.
- Konstantina Chachlaki
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Article
| Open AccessOptochemical control of slow-wave sleep in the nucleus accumbens of male mice by a photoactivatable allosteric modulator of adenosine A2A receptors
The nucleus accumbens integrates sleep and motivation in mice. Here, the authors show sleep induction by increasing the activity of extracellular adenosine from astrocytes and neurons at A2A receptors with a photoactivatable allosteric modulator.
- Koustav Roy
- , Xuzhao Zhou
- & Michael Lazarus
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Article
| Open AccessStress during pubertal development affects female sociosexual behavior in mice
Evidence suggests that stress during development might lead to sexual dysfunction. Here, authors show that pubertal stress disrupted female sexual behavior by reducing activation of nitric oxide synthase-expressing neurons in response to male cues.
- Yassine Bentefour
- & Julie Bakker
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Article
| Open AccessDopamine signaling enriched striatal gene set predicts striatal dopamine synthesis and physiological activity in vivo
Here, the authors report that schizophrenia risk variants mapping to a striatal dopamine-related gene set are associated with increased striatal dopamine synthesis capacity and increased striatal activity during reward anticipation in humans.
- Leonardo Sportelli
- , Daniel P. Eisenberg
- & Giulio Pergola
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Article
| Open AccessAlternative splicing controls teneurin-3 compact dimer formation for neuronal recognition
This study reveals how two splice inserts alter the conformation and dimeric arrangement of the teneurin-3 extracellular region. These insights elucidate the role of teneurin isoforms in neuronal recognition and circuit wiring.
- Christos Gogou
- , J. Wouter Beugelink
- & Dimphna H. Meijer
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Article
| Open AccessMitochondrial complex I deficiency stratifies idiopathic Parkinson’s disease
Idiopathic Parkinson’s disease can be stratified according to the severity of neuronal respiratory complex I deficiency. The emerging disease subtypes show distinct molecular and clinical profiles.
- Irene H. Flønes
- , Lilah Toker
- & Charalampos Tzoulis
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Article
| Open AccessAstroglial Kir4.1 potassium channel deficit drives neuronal hyperexcitability and behavioral defects in Fragile X syndrome mouse model
Fragile X syndrome is a neurodevelopmental disorder with altered neuronal excitability and behavior. Here, the authors show that dysfunction of astroglial Kir4.1 potassium channels drives neuronal and behavioral impairments in a fragile X mouse model.
- Danijela Bataveljic
- , Helena Pivonkova
- & Nathalie Rouach
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Article
| Open AccessHuman connectome topology directs cortical traveling waves and shapes frequency gradients
The factors that determine the direction of traveling waves in the brain are not well understood. Here, the authors show that the sum of incoming structural connection strengths shape both traveling wave direction and frequency gradients.
- Dominik P. Koller
- , Michael Schirner
- & Petra Ritter
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Article
| Open AccessA cluster-randomized trial of water, sanitation, handwashing and nutritional interventions on stress and epigenetic programming
A regulated stress response is essential for healthy child growth and development. Here, the authors show that a nutrition, water, sanitation, and hygiene intervention enhanced adaptive responses of the physiological stress system in early childhood.
- Audrie Lin
- , Andrew N. Mertens
- & Douglas A. Granger
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Article
| Open AccessDynamic corticothalamic modulation of the somatosensory thalamocortical circuit during wakefulness
Layer 6 corticothalamic (L6CT) neurons provide feedback that shapes signaling in sensory pathways. Here, authors show that L6CT neurons are bi-directional modulators of thalamocortical signaling, in a manner dependent upon both L6CT magnitude and synchronization
- Elaida D. Dimwamwa
- , Aurélie Pala
- & Garrett B. Stanley
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Article
| Open AccessCross-modality mapping using image varifolds to align tissue-scale atlases to molecular-scale measures with application to 2D brain sections
Omics data’s diversity and high-dimensionality challenge integration across technologies and with imaging. Here, authors introduce mapping method xIV-LDDMM that estimates geometric and feature transformations to integrate tissue-scale atlases with molecular and cellular-scale data.
- Kaitlin M. Stouffer
- , Alain Trouvé
- & Michael I. Miller
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Article
| Open AccessDisordered clock protein interactions and charge blocks turn an hourglass into a persistent circadian oscillator
Many clock proteins contain intrinsically disordered regions, but how these regions mediate protein interactions is poorly understood. Here, the authors identify charge blocks within a disordered clock protein that regulate circadian timing.
- Meaghan S. Jankowski
- , Daniel Griffith
- & Jennifer M. Hurley
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Article
| Open AccessFunctional connectivity development along the sensorimotor-association axis enhances the cortical hierarchy
Human cortical maturation is organized along the sensorimotor-association axis. Here, the authors investigate in multiple cohorts if the development of functional connectivity during adolescence conforms to this hierarchy.
- Audrey C. Luo
- , Valerie J. Sydnor
- & Theodore D. Satterthwaite
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Article
| Open AccessCortex-wide transcranial localization microscopy with fluorescently labeled red blood cells
Existing neuroimaging tools are still hampered by restricted field-of-view, slow imaging speed or suboptimal spatial resolution. Here, the authors present a fluorescence localization imaging approach aided by sparsely-labeled red blood cells for cortex-wide morphological and functional cerebral angiography with high spatiotemporal resolution.
- Quanyu Zhou
- , Chaim Glück
- & Zhenyue Chen
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Article
| Open AccessSingle cell tracing of Pomc neurons reveals recruitment of ‘Ghost’ subtypes with atypical identity in a mouse model of obesity
Whether and how hypothalamic neurons can lose or change their identity in adulthood has remained elusive. Here, the authors show that mature pro-opiomelanocortin (Pomc) neurons contain invisible ‘Ghost’ subsets with atypical identities that are recruited in response to obesogenic stimuli.
- Stéphane Leon
- , Vincent Simon
- & Carmelo Quarta
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Article
| Open AccessKalium channelrhodopsins effectively inhibit neurons
Kalium channelrhodopsins (KCRs) are promising tools for optogenetic silencing. Here, the authors show that KCRs inhibit cellular excitability in flies, worms, and fish, establishing them as first-line tools for inhibiting diverse types of excitable cells.
- Stanislav Ott
- , Sangyu Xu
- & Adam Claridge-Chang
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Article
| Open AccessSynergism between two BLA-to-BNST pathways for appropriate expression of anxiety-like behaviors in male mice
How distinct circuits get coordinated to allow individuals to express appropriate level of anxiety is unclear. Here, authors show there are two functionally opposing BLA-BNST pathways interacting via the local inhibitory networks to enable anxiety expression with environmental needs.
- Ren-Wen Han
- , Zi-Yi Zhang
- & Bing-Xing Pan
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Article
| Open AccessAltered grid-like coding in early blind people
The contribution of visual experience to the formation of cognitive maps in humans is not well understood. Here, the authors show using fMRI and an imagined navigation paradigm, that sighted people display hexagonal grid-like neural coding, while blind people show neural representations consistent with a square grid.
- Federica Sigismondi
- , Yangwen Xu
- & Roberto Bottini
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Article
| Open AccessFunctional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development
Cell metabolism has emerged as a major factor implicated in human brain evolution. Here, the authors show that an ape-specific enzyme enhances the ability of a human-specific enzyme to increase glutaminolysis and therefore expand the size of the human neocortex.
- Lei Xing
- , Vasiliki Gkini
- & Takashi Namba
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Article
| Open AccessGoal-directed and flexible modulation of syllable sequence within birdsong
Birdsong contains strings of syllables and is essential for their communication. Using a new song decoder to annotates song in a quasi-real-time manner, and rewarding specific syllable sequences, this study shows Bengalese finches can flexibly modify the content of their song in a goal-directed way.
- Takuto Kawaji
- , Mizuki Fujibayashi
- & Kentaro Abe
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Article
| Open AccessBrightness illusions drive a neuronal response in the primary visual cortex under top-down modulation
The neural mechanisms underpinning visual illusions remains poorly understood. Here, the authors recorded the neural responses of mouse primary visual cortex to illusory grating and found delayed responses to illusory brightness, showing that optogenetic inhibition of higher visual areas reduced V1 response to illusions but not to real gratings.
- Alireza Saeedi
- , Kun Wang
- & Masataka Watanabe
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Article
| Open AccessIntracellular magnesium optimizes transmission efficiency and plasticity of hippocampal synapses by reconfiguring their connectivity
How synapses at dendrites are organized to optimize information processing remains elusive. Here, the authors found that intracellular magnesium optimizes transmission, plasticity, and coding capacity of synapses by reconfiguring their connectivity at dendrites.
- Hang Zhou
- , Guo-Qiang Bi
- & Guosong Liu
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Article
| Open AccessPrediction error processing and sharpening of expected information across the face-processing hierarchy
Perception and neural processing of sensory information are influenced by prior expectations. Here the authors show investigate how prior expectations contribute to face processing in the brain.
- Annika Garlichs
- & Helen Blank
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Article
| Open AccessDiverse and asymmetric patterns of single-neuron projectome in regulating interhemispheric connectivity
How interhemispheric connections are organized and how interhemispheric communication are regulated are not fully understood. Here authors delineate the diverse single-neuron projection patterns of interhemispheric connections in mice and uncover their influence on functional dynamics, highlighting the importance of heterotopic projections in interhemispheric communication.
- Yao Fei
- , Qihang Wu
- & Cirong Liu
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Article
| Open AccessPosition- and scale-invariant object-centered spatial localization in monkey frontoparietal cortex dynamically adapts to cognitive demand
The neural basis of spatial localization is poorly understood. Here the authors showed that when planning a reach towards an object, neural coding in the frontoparietal network dynamically changes between allocentric and egocentric spatial reference frames where the transition is controlled by task demands.
- Bahareh Taghizadeh
- , Ole Fortmann
- & Alexander Gail
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Article
| Open AccessCD20/MS4A1 is a mammalian olfactory receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators
How animals sense and properly avoid predators remains incompletely understood. Here, Jiang et al. show that the B cell co-receptor, CD20 also functions as an olfactory receptor and mediates the innate avoidance of predator derived odors.
- Hao-Ching Jiang
- , Sung Jin Park
- & Paul L. Greer
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Article
| Open AccessPerceptography unveils the causal contribution of inferior temporal cortex to visual perception
The precise role that inferotemporal cortex plays in object recognition remains poorly understood. Here, the authors combine high-throughput behavioral optogenetics in non-human primates with machine learning to graphically capture perceptual events evoked by local stimulation in the high-level visual cortex.
- Elia Shahbazi
- , Timothy Ma
- & Arash Afraz
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Article
| Open AccessCdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila
Mitochondrial fission, performed by Drp1, is carefully regulated, particularly in neurons. Here, the authors examine Drosophila Cdk8/CDK19 function in mitochondrial fission and uncover a role phosphorylating Drp1 in the cytoplasm and show overexpression suppresses a Parkinson’s disease model.
- Jenny Zhe Liao
- , Hyung-lok Chung
- & Esther M. Verheyen
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Article
| Open AccessStructural basis for antiepileptic drugs and botulinum neurotoxin recognition of SV2A
SV2A is a receptor for botulinum neurotoxin (BoNT) and new generation antiepileptic drugs (AEDs). Here the authors report cryo-EM structures of SV2A in complex with BoNT receptor binding domain and AEDs highlighting the difference in the binding affinity between AEDs.
- Atsushi Yamagata
- , Kaori Ito
- & Mikako Shirouzu
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Article
| Open AccessReconstruction of macroglia and adult neurogenesis evolution through cross-species single-cell transcriptomic analyses
Macroglia are neural cells that have garnered less interest than neurons despite their crucial functions including neurogenesis. Here the authors use sequencing from several species to investigate the evolution of macroglia and of adult neurogenesis.
- David Morizet
- , Isabelle Foucher
- & Laure Bally-Cuif
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Article
| Open AccessRobust compression and detection of epileptiform patterns in ECoG using a real-time spiking neural network hardware framework
Costa et al. designed a modular spiking neural network in a neuromorphic device with heterogeneous silicon neurons that remotely detects epileptiform discharges and High Frequency Oscillations in intra-operative EEG during epilepsy surgery in real-time.
- Filippo Costa
- , Eline V. Schaft
- & Johannes Sarnthein
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Article
| Open AccessDistinct information conveyed to the olfactory bulb by feedforward input from the nose and feedback from the cortex
How the feedforward information from the nose and feedback from the cortex interact in the olfactory bulb is not fully understood. Here, by imaging olfactory sensory neurons and cortical projections to the olfactory bulb, the authors show that sensory transformations contained within both streams.
- Joseph D. Zak
- , Gautam Reddy
- & Venkatesh N. Murthy
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Article
| Open AccessCXCL5 activates CXCR2 in nociceptive sensory neurons to drive joint pain and inflammation in experimental gouty arthritis
Here, the authors demonstrate that CXCL5 expression is increased in ankle joints of gouty arthritis model mice. CXCL5-neuronal CXCR2-TRPA1 axis contributes to gouty arthritis pain, neutrophil influx and joint inflammation.
- Chengyu Yin
- , Boyu Liu
- & Boyi Liu
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Article
| Open AccessConjunctive encoding of exploratory intentions and spatial information in the hippocampus
The hippocampus maps space, but its role in encoding investigatory intentions is unclear. Here the authors show that certain CA1 neurons encode both spatial information and animals’ intention to explore, depending on input from lateral entorhinal cortex.
- Yi-Fan Zeng
- , Ke-Xin Yang
- & Ning Zhou
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Article
| Open AccessAlkyne-tagged SERS nanoprobe for understanding Cu+ and Cu2+ conversion in cuproptosis processes
Simultaneously quantifying mitochondrial Cu+ and Cu2+ levels is vital for understanding the molecular mechanism of mitochondria-related biological events. Here the authors report an alkynyl-labeled SERS probe to simultaneously monitor free Cu+ and Cu2+ in mitochondria, and unveil their roles during ischemia and cuproptosis processes.
- Sihan Zhang
- , Yuxiao Mei
- & Yang Tian
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Article
| Open AccessA hippocampus-accumbens code guides goal-directed appetitive behavior
The dorsal hippocampus plays an important role for spatial memory, but how its outputs guide behavior is not fully understood. Here, the authors show that nucleus accumbens-specific hippocampal projection neurons carry a highly conjunctive code of spatial and action information that directs spatial reward memory-guided appetitive behaviors.
- Oliver Barnstedt
- , Petra Mocellin
- & Stefan Remy
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Article
| Open AccessNeurocomputational mechanisms involved in adaptation to fluctuating intentions of others
Humans often interact without knowing the cooperative or competitive intentions of others. Here, the authors determined the neurocomputational mechanisms engaged in adapting to fluctuating intentions of others over repeated social interactions.
- Rémi Philippe
- , Rémi Janet
- & Jean-Claude Dreher
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Article
| Open AccessStimulus encoding by specific inactivation of cortical neurons
How neural ensembles encode information remains poorly understood. Here, the authors identify “offsembles”—neurons that are specifically inactivated by sensory stimuli—which, when combined with “onsemble” neurons that are turned on by the stimulus, provide enhanced encoding power to the cortex.
- Jesús Pérez-Ortega
- , Alejandro Akrouh
- & Rafael Yuste
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Article
| Open AccessSubthalamic stimulation modulates context-dependent effects of beta bursts during fine motor control
How movement speed is neurally modulated remains poorly understood. Here, the authors recorded invasive brain signals in Parkinson’s disease patients during drawing and deep brain stimulation, showing a context-dependent relationship between reductions of movement acceleration and dynamic activity of the basal ganglia.
- Manuel Bange
- , Gabriel Gonzalez-Escamilla
- & Sergiu Groppa
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Article
| Open AccessNeural signatures of indirect pathway activity during subthalamic stimulation in Parkinson’s disease
Subthalamic deep brain stimulation produces evoked resonant neural activity (ERNA) which has been linked to therapeutic benefit. Using a multimodal approach, the authors propose that ERNA reflects activation of the basal ganglia indirect pathway network.
- Leon A. Steiner
- , David Crompton
- & Luka Milosevic
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Article
| Open AccessMultisensory flicker modulates widespread brain networks and reduces interictal epileptiform discharges
Repetitive audio-visual stimulation, or sensory flicker, can modulate oscillations in a non-invasive manner. Here the authors demonstrate the potential of flicker in individuals with epilepsy undergoing intracranial seizure monitoring.
- Lou T. Blanpain
- , Eric R. Cole
- & Annabelle C. Singer
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Article
| Open AccessMultiplicative joint coding in preparatory activity for reaching sequence in macaque motor cortex
Understanding the link between multiple movement elements and sequence-related responses in the motor cortex remains elusive. This study reveals a multiplicative joint coding mechanism during motor preparation which transfers to additive during execution, potentially explaining the linear readout of elemental movements.
- Tianwei Wang
- , Yun Chen
- & He Cui
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Article
| Open AccessTension activation of mechanosensitive two-pore domain K+ channels TRAAK, TREK-1, and TREK-2
TRAAK, TREK-1 and TREK-2 are mechanosensitive potassium channels involved in action potential propagation among other roles. Here, authors quantify their tension response and show ultrasound can generate tension to activate ion channels.
- Ben Sorum
- , Trevor Docter
- & Stephen G. Brohawn
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Article
| Open AccessDynamics of collective cooperation under personalised strategy updates
Collective cooperation is found across many social and biological systems. Here, the authors find that infrequent hub updates promote the emergence of collective cooperation and develop an algorithm that optimises collective cooperation with update rates.
- Yao Meng
- , Sean P. Cornelius
- & Aming Li
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Article
| Open AccessElevated ozone disrupts mating boundaries in drosophilid flies
Some atmospheric pollutants may disrupt chemical communication in insects. Here, the authors show that exposure to elevated ozone disrupts pheromone-mediated mate recognition and increases hybridization in laboratory colonies of four Drosophila species.
- Nan-Ji Jiang
- , Xinqi Dong
- & Markus Knaden
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