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| Open AccessDecomposing cortical activity through neuronal tracing connectome-eigenmodes in marmosets
The relationship between neuroanatomical connections and functional activity is still unclear. Using graph signal processing, the authors show neuronal tracing connectome eigenmodes constrain cortical activity in marmosets.
- Jie Xia
- , Cirong Liu
- & Wei Liao
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Article
| Open AccessNanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in mice
Ultrasound may be used to non-invasively modulate the brain. Here the authors describe acoustic nanobubble-mediated ultrasound stimulation of specific brain region in male mice.
- Xuandi Hou
- , Jianing Jing
- & Lei Sun
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Review Article
| Open AccessNeuropathogenesis-on-chips for neurodegenerative diseases
This review focuses on recent advances in on-chip platforms for patient-like in vitro modeling of the pathology of neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases as well as Amyotrophic lateral sclerosis. The authors advocate for broader usage of these human-relevant models in the academic and pharmaceutical fields.
- Sarnai Amartumur
- , Huong Nguyen
- & Chaejeong Heo
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Article
| Open AccessDistributed neural representations of conditioned threat in the human brain
Discriminating threat from safety is critical for humans to navigate their environment. Here, the authors show that neural representations of threat and safety are distributed across brain systems that are robustly decoded across threat paradigms.
- Zhenfu Wen
- , Edward F. Pace-Schott
- & Mohammed R. Milad
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Article
| Open AccessSynapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles
How synaptic vesicles (SVs) are clustered at the presynapse is suggestive of anchoring processes counteracting their diffusion. Here, the authors co-track recycling and reserve SVs in live neurons to find that Synapsin 2a tetramerization dynamically immobilizes reserve SVs at the presynapse.
- Shanley F. Longfield
- , Rachel S. Gormal
- & Frédéric A. Meunier
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Article
| Open AccessA single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer’s disease
Vascular pathology may play important early role in Alzheimer’s disease (AD). Here, the authors show that β-amyloid induces transcriptomic signatures associated with accelerated apoptosis, impaired function and AD risk in human brain microvasculature.
- Stergios Tsartsalis
- , Hannah Sleven
- & Paul M. Matthews
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Article
| Open AccessIdentification of four biotypes in temporal lobe epilepsy via machine learning on brain images
Brain imaging-based disease progression modelling is a promising technique for disease stratification. Here the authors characterize distinct ‘trajectories’ of brain atrophy in temporal lobe epilepsy and identify four subtypes with distinct neuroanatomical signatures.
- Yuchao Jiang
- , Wei Li
- & Dongmei An
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Article
| Open AccessNumerosity estimation of virtual humans as a digital-robotic marker for hallucinations in Parkinson’s disease
Virtual reality, robotics and digital online technologies reveal heightened visual overestimation when estimating the number of humans, indexing presence hallucinations in healthy participants and patients with Parkinson’s disease.
- Louis Albert
- , Jevita Potheegadoo
- & Olaf Blanke
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Article
| Open AccessIntercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells
How the neighboring cells contribute to the survival and functions of neuronal cells remains elusive. Here, authors identified the cell-cell interactions between retinal ganglion cells (RGCs) and other cells after RGC injury and discovered the μ-opioid receptor promotes RGC resilience.
- Cheng Qian
- , Ying Xin
- & Jiang Qian
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Article
| Open AccessSilencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations
Current approaches possibly cannot unambiguously distinguish the unique contributions of feedback inhibition versus feedforward inhibition to oscillatory events. Here authors show that a loss of CA1 pyramidal cell transmission, resulting in feedback inhibition reduction, leads to spatially triggered high-frequency oscillatory events; these events were like place cells in their spatial extent and localized to small regions in CA1.
- Chinnakkaruppan Adaikkan
- , Justin Joseph
- & Thomas J. McHugh
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Article
| Open AccessA multi-demand operating system underlying diverse cognitive tasks
A consistent set of brain areas is engaged across diverse cognitive tasks. Here, the authors reveal a unifying latent brain state that predicts performance across seven tasks, linking a core control network to cognitive flexibility and adaptive behaviors.
- Weidong Cai
- , Jalil Taghia
- & Vinod Menon
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Article
| Open AccessLocal orchestration of distributed functional patterns supporting loss and restoration of consciousness in the primate brain
The brain’s role in supporting consciousness is unclear. Here, authors show that global markers of consciousness in macaque cortex are suppressed by many anaesthetics, and restored by local stimulation of a thalamic nucleus that also induces awakening.
- Andrea I. Luppi
- , Lynn Uhrig
- & Rodrigo Cofre
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Article
| Open AccessIdentification of gene regulatory networks affected across drug-resistant epilepsies
Epilepsy is a chronic, heterogeneous disease with an urgent need for novel therapies. Here, the authors show a systematic comparison of the global molecular signature of refractory epilepsies elucidating the key mechanisms of the disease pathology.
- Liesbeth François
- , Alessia Romagnolo
- & Eleonora Aronica
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Article
| Open AccessPCDHA9 as a candidate gene for amyotrophic lateral sclerosis
Genetic mutations are found in only 15% of sporadic ALS. Here, authors identify PCDHA9 as a candidate ALS gene and elucidate detailed underlying pathogenesis using mice with Pcdhα9 mutations that develop typical ALS phenotype and hallmark pathology.
- Jie Zhong
- , Chaodong Wang
- & Zhiheng Xu
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Article
| Open AccessAgeing impairs the regenerative capacity of regulatory T cells in mouse central nervous system remyelination
Factors limiting CNS remyelination with age are poorly understood. Here the authors show that aged Treg lose capacity to support CNS remyelination in mice, which can be restored in a young environment.
- Alerie Guzman de la Fuente
- , Marie Dittmer
- & Denise C. Fitzgerald
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Article
| Open AccessPrefrontal control of superior colliculus modulates innate escape behavior following adversity
Significant aversive experience can cause lasting behavioral changes due to shifts in arousal thresholds and filter mechanisms. Here, in male mice, the authors identify a change in a neural circuit, underlying adversity driven enhanced threat response.
- Ami Ritter
- , Shlomi Habusha
- & Oded Klavir
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Article
| Open AccessTemporally organized representations of reward and risk in the human brain
It is unclear how reward and risk are temporally organized in the human brain. Here, the authors demonstrate both sequential and parallel encoding of decision variables, and the role of anterior insula in reward- and risk-prediction error.
- Vincent Man
- , Jeffrey Cockburn
- & John P. O’Doherty
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Article
| Open AccessNeural timescales reflect behavioral demands in freely moving rhesus macaques
The functional relevance of neural timescales is not fully understood. Here the authors demonstrate that neural timescales change with behavioral demands in freely moving macaques.
- Ana M. G. Manea
- , David J.-N. Maisson
- & Jan Zimmermann
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Article
| Open AccessFUS unveiled in mitochondrial DNA repair and targeted ligase-1 expression rescues repair-defects in FUS-linked motor neuron disease
Dysfunction of Fused in Sarcoma (FUS) leads to increased mitochondrial DNA (mtDNA) damage, mutations, and mitochondrial dysfunction. This study shows that FUS collaborates with mtDNA Ligase IIIα to maintain mtDNA repair and integrity.
- Manohar Kodavati
- , Haibo Wang
- & Muralidhar L. Hegde
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Article
| Open AccessIdentification of the growth cone as a probe and driver of neuronal migration in the injured brain
Structure and functions of the tip of migratory neurons remain elusive. Here, the authors show that the PTPσ-expressing growth cone senses extracellular matrix changes and drives neuronal migration in the injured brain, leading to the functional recovery.
- Chikako Nakajima
- , Masato Sawada
- & Kazunobu Sawamoto
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Article
| Open AccessA Protein Misfolding Shaking Amplification-based method for the spontaneous generation of hundreds of bona fide prions
To study neurodegenerative prion diseases, a method (PMSA) for generating prions spontaneously is presented. Applied to 380+ different prion proteins, their tendency to become pathogenic was ranked, illuminating their formation process.
- Hasier Eraña
- , Cristina Sampedro-Torres-Quevedo
- & Joaquín Castilla
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Article
| Open AccessOrganization of reward and movement signals in the basal ganglia and cerebellum
How the brain transforms reward information into actions remains poorly understood. Here, the authors found that reward expectation and sensorimotor signals are more pronounced in the output of the basal ganglia than its input or the cerebellar cortex, implying that the transformation of reward signals into motor signals is not hierarchically organized.
- Noga Larry
- , Gil Zur
- & Mati Joshua
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Article
| Open AccessActivity-dependent compartmentalization of dendritic mitochondria morphology through local regulation of fusion-fission balance in neurons in vivo
The mechanisms regulating mitochondrial architecture in neurons remain unclear. The authors report that in dendrites, mitochondria structure is specified by the CAMKK2-AMPK pathway through compartment-specific and activity-dependent levels of fission.
- Daniel M. Virga
- , Stevie Hamilton
- & Tommy L. Lewis Jr
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Article
| Open AccessA persistent prefrontal reference frame across time and task rules
The prefrontal cortex (PFC) is involved in rule-coding and long-term memory. Here, the authors identified a stably active neuronal ensemble in the mouse medial PFC in an olfaction-guided spatial memory task, which showed stable tuning to task features across time, rule-reversal, and context changes.
- Hannah Muysers
- , Hung-Ling Chen
- & Marlene Bartos
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Article
| Open AccessmicroRNA-33 controls hunger signaling in hypothalamic AgRP neurons
AgRP neurons regulate feeding behavior by promoting signals of hunger. Here, the authors show that miR-33, represses the activity of AgRP neurons, and selective loss of miR-33 in AgRP neurons promotes obesity and metabolic dysfunction in mice.
- Nathan L. Price
- , Pablo Fernández-Tussy
- & Carlos Fernández-Hernando
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Article
| Open AccessWalking modulates visual detection performance according to stride cycle phase
“Visual performance might vary during natural behaviour such as walking. Here, the authors use wireless virtual reality to show that oscillations in performance on a visual detection task were systematically linked to the phase of the stride cycle.”
- Matthew J. Davidson
- , Frans A. J. Verstraten
- & David Alais
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Article
| Open AccessSocial buffering in rats reduces fear by oxytocin triggering sustained changes in central amygdala neuronal activity
After rats were trained to fear a sound, they showed less fear when another rat was nearby and this calming effect lasted when the other rat was removed. Both reductions required oxytocin signaling from the hypothalamus to the central amygdala.
- Chloe Hegoburu
- , Yan Tang
- & Ron Stoop
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Article
| Open AccessControl of feeding by a bottom-up midbrain-subthalamic pathway
Periaqueductal gray (PAG) inputs control hunting, but foraging-inducing PAG cells were unidentified. Here, authors show that in mice activity in the projection of vgat PAG cells to the zona incerta is sufficient and necessary for food-seeking.
- Fernando M. C. V. Reis
- , Sandra Maesta-Pereira
- & Avishek Adhikari
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Article
| Open AccessHypothalamic astrocyte NAD+ salvage pathway mediates the coupling of dietary fat overconsumption in a mouse model of obesity
The cellular levels of the critical coenzyme nicotinamide adenine dinucleotide (NAD)+ depend on its salvage pathway. Here, the authors show that the NAD+ salvage pathway in hypothalamic astrocytes is activated to promote obesity in high fat diet-fed mice.
- Jae Woo Park
- , Se Eun Park
- & Min-Seon Kim
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Article
| Open AccessKdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons
Kdm1a is a histone demethylase implicated in intellectual disability. Here, the authors show that removing Kdm1a in neurons of the adult mouse forebrain disrupts silencing of nonneuronal genes and chromatin organization, emphasizing its role in preserving neuronal genome integrity.
- Beatriz del Blanco
- , Sergio Niñerola
- & Ángel Barco
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Article
| Open AccessBHLHE40/41 regulate microglia and peripheral macrophage responses associated with Alzheimer’s disease and other disorders of lipid-rich tissues
Factors regulating lipid and lysosomal clearance in microglia and peripheral macrophage are not known. Here, authors nominate and validate transcription factors BHLHE40 and BHLHE41 as regulators of these processes in health and disease.
- Anna Podleśny-Drabiniok
- , Gloriia Novikova
- & Alison Mary Goate
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Article
| Open AccessFully bioresorbable hybrid opto-electronic neural implant system for simultaneous electrophysiological recording and optogenetic stimulation
Bioresorbable neural implants offer a promising solution to the challenges of secondary surgeries required for the removal of implanted devices. Here, the authors introduce a fully bioresorbable flexible hybrid opto-electronic system for simultaneous electrophysiological recording and optogenetic stimulation.
- Myeongki Cho
- , Jeong-Kyu Han
- & Ki Jun Yu
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Article
| Open AccessAn artificial protein modulator reprogramming neuronal protein functions
Direct modulation of protein by artificial catalysts as enzyme mimetics remains hindered by the lack of highly efficient catalytic centers. Here, the authors present the development of artificial protein modulators (APROMs) with protein phosphatase-like characteristics, catalytically reprogram the biological function of α-synuclein.
- Peihua Lin
- , Bo Zhang
- & Daishun Ling
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Article
| Open AccessImproved modeling of human vision by incorporating robustness to blur in convolutional neural networks
The phenomenon of blurry or degraded visual input in humans has been overlooked in the training of convolutional neural networks (CNNs). Here, the authors show that blur-trained CNNs outperform standard CNNs in predicting neural responses to objects and show improved correspondence with human perception.
- Hojin Jang
- & Frank Tong
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Article
| Open AccessFunctional analysis of the human perivascular subarachnoid space
Functional implications of subarachnoid space anatomy remain unclear. Here, the authors show by human in vivo imaging that an intrathecal tracer propagates antegrade along the major cerebral arteries within a perivascular subarachnoid space facilitating tracer passage towards the brain.
- Per Kristian Eide
- & Geir Ringstad
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Article
| Open AccessSpecific pharmacological and Gi/o protein responses of some native GPCRs in neurons
G protein responses mediated by GPCRs may differ depending on their environment. Here, using highly sensitive Gi/o sensors, the authors reveal the specific pharmacological and Gi/o protein responses of some native GPCRs in neurons, and the influence of G protein composition.
- Chanjuan Xu
- , Yiwei Zhou
- & Jianfeng Liu
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Article
| Open AccessA spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution
The dorsal pons in the brainstem is packed with clusters of neurons, including the parabrachial nucleus, that are involved in many vital functions. Here, authors use single nucleus RNA sequencing and MERFISH to create a spatially defined transcriptional atlas of this region.
- Stefano Nardone
- , Roberto De Luca
- & Bradford B. Lowell
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Article
| Open AccessGenetic architecture of the structural connectome
The structural connectome is the complete set of anatomical connections between brain cells. Here, the authors perform a genome-wide association study of white-matter structural connectivity in the human brain, finding 30 variants influencing the density of myelinated connections between brain regions.
- Michael Wainberg
- , Natalie J. Forde
- & Shreejoy J. Tripathy
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Article
| Open AccessDistinct neurochemical influences on fMRI response polarity in the striatum
The relationship between striatal vascular and neural activity is not fully understood. Here the authors found neuronal activity inadequately explains striatal hemodynamic polarity, challenging classic fMRI interpretations.
- Domenic H. Cerri
- , Daniel L. Albaugh
- & Yen-Yu Ian Shih
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Article
| Open AccessA phase I/IIa safety and efficacy trial of intratympanic gamma-secretase inhibitor as a regenerative drug treatment for sensorineural hearing loss
Pharmacological inhibition of gamma-secretase induced partial recovery of hearing in animal models. Here, the authors present the safety and efficacy results and key learnings of the First in Human Phase I/IIa study of a gamma-secretase inhibitor in patients with acquired Hearing Loss.
- Anne G. M. Schilder
- , Stephan Wolpert
- & Athanasios G. Bibas
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Article
| Open AccessDistributed feature representations of natural stimuli across parallel retinal pathways
The precise organization of ON bipolar cells in the visual system remains poorly understood. Here, the authors discover that the mammalian ON bipolar pathway is divided into two streams that distribute the encoding of spatial and temporal information from naturalistic visual stimuli, respectively.
- Jen-Chun Hsiang
- , Ning Shen
- & Daniel Kerschensteiner
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Article
| Open AccessGamma oscillatory complexity conveys behavioral information in hippocampal networks
Specific gamma frequency oscillations are supposed to differentially route information within the hippocampal formation. Here, the authors show that while hippocampal gamma oscillations are more diverse than previously reported, this variability is modulated by behavior and learning.
- Vincent Douchamps
- , Matteo di Volo
- & Romain Goutagny
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Review Article
| Open AccessDiagnosis and management of subarachnoid haemorrhage
Aneurysmal subarachnoid haemorrhage, with its multisystem effects, presents a substantial challenge to clinicians. Here, the authors show the necessity for comprehensive multidisciplinary care and the urgent need for largescale studies to validate standardised treatment protocols for improved outcomes.
- Suneesh Thilak
- , Poppy Brown
- & Tonny Veenith
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Article
| Open AccessDendritic mGluR2 and perisomatic Kv3 signaling regulate dendritic computation of mouse starburst amacrine cells
How starburst amacrine cell (SAC) dendrites transform concentrically distributed synaptic inputs into branch-specific directional outputs is not fully understood. Here the authors report that dendritic mGluR2 signaling and somatic Kv3-mediated shunting coordinately implement SAC dendritic direction selectivity.
- Héctor Acarón Ledesma
- , Jennifer Ding
- & Wei Wei
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Article
| Open AccessData leakage inflates prediction performance in connectome-based machine learning models
The effects of data leakage on predictive models in neuroimaging studies are not well understood. Here, the authors show that data leakage via feature selection and repeated subjects drastically inflates prediction performance, whereas other forms of leakage have more minor effects.
- Matthew Rosenblatt
- , Link Tejavibulya
- & Dustin Scheinost
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Article
| Open AccessComparative connectomics of dauer reveals developmental plasticity
How the dauer, an alternative developmental stage in nematodes, exhibits distinct behavioral traits remains unclear. Here, the authors reveal the neural circuitry underlying these distinctions by reconstructing the dauer connectome and comparing it with other stages.
- Hyunsoo Yim
- , Daniel T. Choe
- & Junho Lee
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Article
| Open AccessImportin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons
Myelinated axons vary in diameter by over 100-fold. Here, the authors identify a role for the nuclear transport receptor importin 13 in axon diameter growth and corresponding increases to conduction speed along myelinated axons.
- Jenea M. Bin
- , Daumante Suminaite
- & David A. Lyons
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Article
| Open AccessTBC1D23 mediates Golgi-specific LKB1 signaling
The LKB1 signaling is differentially regulated and has distinct functions at different subcellular compartments. Tu et al reports that TBC1D23 specifically regulates Golgi-LKB1 signaling and link this pathway to neurodevelopment disorders.
- Yingfeng Tu
- , Qin Yang
- & Da Jia
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Article
| Open AccessBicarbonate signalling via G protein-coupled receptor regulates ischaemia-reperfusion injury
The acid–base balance regulates cellular responses, but little has been known about its molecular mechanism. Here, the authors unveil a bicarbonate-sensing GPCR, GPR30, that underlies cerebral ischemia–reperfusion injury by regulating blood flow recovery.
- Airi Jo-Watanabe
- , Toshiki Inaba
- & Takehiko Yokomizo
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