Focus 26 January 2021

From brain to behaviour

The aim of this page is to provide a snapshot of some of the most exciting work on the brain published in Nature Communications. We cover a wide variety of areas and organisms, ranging from neurophysiological and neurodevelopmental studies in model organisms to systems neuroscience to cognitive neuroscience and psychology.

Featured articles

A geometrical solution underlies general neural principle for serial ordering

How the brain sequentially encodes knowledge is not fully understood. Here authors propose a geometric framework for the elusive neural principles of serial reasoning and sequence encoding. Neural representations are theorized to align along a learned mental line, solving serial position and transitive inference tasks.
- Gabriele Di Antonio
- Sofia Raglio
- Maurizio Mattia
ArticleOpen Access19 Sep 2024 Nature Communications
Distinct codes for environment structure and symmetry in postrhinal and retrosplenial cortices

Whether and how the postrhinal (POR) and retrosplenial (RSC) cortices interact with each other and impact downstream allocentric representations are not fully understood. Here authors present single neuron recordings from freely moving rats exploring different environments to reveal distinct egocentric (self-centered) and allocentric (world-centered) coding frameworks for landmarks and boundaries in interconnected cortical regions.
- Patrick A. LaChance
- Michael E. Hasselmo
ArticleOpen Access13 Sep 2024 Nature Communications
A distinct neuronal ensemble of prelimbic cortex mediates spontaneous pain in rats with peripheral inflammation

Neural mechanisms underlying spontaneous pain are not fully understood. Here authors identify a unique neuronal ensemble in the PL of rats with chronic inflammation, encoding spontaneous pain independently. Activating this ensemble triggers pain-like behaviors, while inhibiting it alleviates pain and accelerates recovery.
- Longyu Ma
- Lupeng Yue
- Ming Yi
ArticleOpen Access10 Sep 2024 Nature Communications
Network state changes in sensory thalamus represent learned outcomes

The computational role of individual sensory thalamic nuclei in flexible encoding during adaptive behaviors is not fully understood. Here authors, using longitudinal deep brain two-photon calcium imaging, show that changes in mouse auditory thalamus single cell and neuronal population dynamics are predictive of task outcome in cross-modal associative learning.
- Masashi Hasegawa
- Ziyan Huang
- Jan Gründemann
ArticleOpen Access7 Sep 2024 Nature Communications
Gliovascular transcriptional perturbations in Alzheimer’s disease reveal molecular mechanisms of blood brain barrier dysfunction

Systematic studies are needed to discover molecular determinants of blood brain barrier dysfunction in Alzheimer’s disease. This study identifies perturbed pericytic SMAD3-astrocytic VEGFA interactions as a potential driver of this dysfunction.
- Özkan İş
- Xue Wang
- Nilüfer Ertekin-Taner
ArticleOpen Access20 Jun 2024 Nature Communications
Plasma proteomics identify biomarkers predicting Parkinson’s disease up to 7 years before symptom onset

Parkinson’s disease is lacking easily accessible biomarkers. Here the authors show, that targeted blood proteomics is feasible to identify the patients and to predict the phenoconvertion in prodromal subjects up to 7 years before symptom onset.
- Jenny Hällqvist
- Michael Bartl
- Brit Mollenhauer
ArticleOpen Access18 Jun 2024 Nature Communications
Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology

Lewy body diseases exhibit notable clinical and pathological heterogeneity. Here, the authors found three distinct trajectories of Lewy body pathology that are associated with different clinicopathological characteristics.
- Sophie E. Mastenbroek
- Jacob W. Vogel
- Oskar Hansson
ArticleOpen Access15 Jun 2024 Nature Communications
Multiomic ALS signatures highlight subclusters and sex differences suggesting the MAPK pathway as therapeutic target

Multiomic brain tissue analysis identified sex-specific molecular changes in Amyotrophic lateral sclerosis (ALS), revealing subgroups within the disease and pointing to the MAPK pathway as an early disease mechanism and potential therapeutic target.
- Lucas Caldi Gomes
- Sonja Hänzelmann
- Paul Lingor
ArticleOpen Access7 Jun 2024 Nature Communications
EEG decoders track memory dynamics

Successful memorization could be decoded from brain activity. Here the authors decode human memory success from EEG recordings, suggesting memory is linked to context.
- Yuxuan Li
- Jesse K. Pazdera
- Michael J. Kahana
ArticleOpen Access6 Apr 2024 Nature Communications
Spatial transcriptomics reveals molecular dysfunction associated with cortical Lewy pathology

The impact of α-synuclein aggregates on neurons has been unclear. Here, the authors identify a Lewy Associated Molecular Dysfunction from Aggregates (LAMDA) signature in inclusion bearing neurons in human brain and a mouse model of α-synucleinopathy.
- Thomas M. Goralski
- Lindsay Meyerdirk
- Michael X. Henderson
ArticleOpen Access26 Mar 2024 Nature Communications
The influence of cortical activity on perception depends on behavioral state and sensory context

The mechanistic link between cortical activity and behaviors remains largely unclear. Here authors show that targeted holographic photostimulation of mouse visual cortex during a detection task alters performance based on the animal’s state and visual stimulus conditions, highlighting the dynamic influence of cortical activity on perception and behavior.
- Lloyd E. Russell
- Mehmet Fişek
- Michael Häusser
ArticleOpen Access19 Mar 2024 Nature Communications
Silencing 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
ArticleOpen Access11 Mar 2024 Nature Communications
Local 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
ArticleOpen Access11 Mar 2024 Nature Communications
Numerosity 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
ArticleOpen Access12 Mar 2024 Nature Communications
A transient protein folding response targets aggregation in the early phase of TDP-43-mediated neurodegeneration

The etiology of TDP-43 proteinopathy in ALS and FTD is complex. Here, the authors show that prior to disease onset in the rNLS8 mouse model, cortex neurons elicit a transient increase in protective chaperones that combat TDP-43 aggregation.
- Rebecca San Gil
- Dana Pascovici
- Adam K. Walker
ArticleOpen Access19 Feb 2024 Nature Communications
Reduced progranulin increases tau and α-synuclein inclusions and alters mouse tauopathy phenotypes via glucocerebrosidase

Neurodegenerative diseases often co-accumulate several disease-associated proteins. Here, the authors show that reduction of progranulin, a protein associated with TDP-43, also increases accumulation of tau and a-synuclein via glucocerebrosidase.
- Hideyuki Takahashi
- Sanaea Bhagwagar
- Stephen M. Strittmatter
ArticleOpen Access16 Feb 2024 Nature Communications
Integrating single-cell and spatially resolved transcriptomic strategies to survey the astrocyte response to stroke in male mice

Astrocytes adopt diverse states in response to brain injuries. Here, the authors develop a platform for spatially resolved, single-cell transcriptomics and proteomics, called tDISCO (tissue-digital microfluidic isolation of single cells for -Omics) to uncover the spatial boundaries of molecularly distinct reactive astrocyte populations in stroke.
- Erica Y. Scott
- Nickie Safarian
- Maryam Faiz
ArticleOpen Access21 Feb 2024 Nature Communications
Ageing 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
ArticleOpen Access11 Mar 2024 Nature Communications
Efficacy and safety of using auditory-motor entrainment to improve walking after stroke: a multi-site randomized controlled trial of InTandem^TM

Post-stroke walking impairment is a significant public health concern. Here, the authors perform an interventional, randomized controlled trial evaluating the efficacy and safety of InTandem™, an autonomous neurorehabilitation system utilizing auditory-motor entrainment to improve walking after stroke.
- Louis N. Awad
- Arun Jayaraman
- Sabrina R. Taylor
ArticleOpen Access8 Feb 2024 Nature Communications
Grid-like entorhinal representation of an abstract value space during prospective decision making

Values of choice options often change over time. Here, the authors show that during prospective decision making the entorhinal cortex encodes changing values using a grid-like representation, suggesting the formation of a cognitive value map.
- Alexander Nitsch
- Mona M. Garvert
- Christian F. Doeller
ArticleOpen Access9 Feb 2024 Nature Communications
Distinct value computations support rapid sequential decisions

How animals determine the value of the environment for motivation and error-based learning remains unclear. Here, the authors found that rats use multiple distinct algorithms to compute the value of the environment for rapid sequential actions on single trials.
- Andrew Mah
- Shannon S. Schiereck
- Christine M. Constantinople
ArticleOpen Access21 Nov 2023 Nature Communications
Emergence of syntax and word prediction in an artificial neural circuit of the cerebellum

The role of the cerebellum in language processing remains unclear. Here, the authors use a biologically-constrained artificial cerebellar neural network to reveal a dual role of single circuit computation in syntax and word prediction.
- Keiko Ohmae
- Shogo Ohmae
ArticleOpen Access31 Jan 2024 Nature Communications
Latent representations in hippocampal network model co-evolve with behavioral exploration of task structure

How mechanisms of single-cell plasticity lead to task-dependent cognitive maps remains unclear. Here, the authors show that this model of hippocampus shows that cooperation between local plasticity and reinforcement learning of behavior can lead to task-specific latent representations.
- Ian Cone
- Claudia Clopath
ArticleOpen Access23 Jan 2024 Nature Communications
Oligodendrocyte calcium signaling promotes actin-dependent myelin sheath extension

The cell biological mechanisms that govern myelin sheath extension remain incompletely understood. Here, the authors find that calcium signaling in oligodendrocytes is required for the actin-dependent extension of myelin sheaths.
- Manasi Iyer
- Husniye Kantarci
- J. Bradley Zuchero
ArticleOpen Access4 Jan 2024 Nature Communications
Behavioral representational similarity analysis reveals how episodic learning is influenced by and reshapes semantic memory

Pre-existing semantic knowledge provides an organizational structure for episodic memories. Here, the authors show that episodic learning systematically shapes this semantic space depending on how learners engage with material and the strength of prior associations.
- Catherine R. Walsh
- Jesse Rissman
ArticleOpen Access20 Nov 2023 Nature Communications
Early-to-mid stage idiopathic Parkinson’s disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females

Men are at a greater risk to develop Parkinson’s disease (PD). However, Hefeng and team revealed enhanced cytotoxicity and terminal differentiation in CD8 T cells of early-to-mid stage idiopathic PD, especially for females, using systems immunology.
- Christophe M. Capelle
- Séverine Ciré
- Feng Q. Hefeng
ArticleOpen Access20 Nov 2023 Nature Communications
Multifaceted information-seeking motives in children

Knowledge can impact children’s emotion, cognition, and action. The authors show that when seeking information, children consider if information is useful, positive, and lowers uncertainty, with the emphasis on these considerations changing with age.
- Gaia Molinaro
- Irene Cogliati Dezza
- Tali Sharot
ArticleOpen Access7 Sep 2023 Nature Communications
FEAST: A flow cytometry-based toolkit for interrogating microglial engulfment of synaptic and myelin proteins

When and how microglia engulf synapses and myelin is still unclear. Here, the authors provide a suite of flow cytometry-based approaches to quantify engulfment, paving the way for high-throughput assessment of microglial function in health and disease.
- Lasse Dissing-Olesen
- Alec J. Walker
- Beth Stevens
ArticleOpen Access27 Sep 2023 Nature Communications
VE-cadherin in arachnoid and pia mater cells serves as a suitable landmark for in vivo imaging of CNS immune surveillance and inflammation

How the leptomeninges establish CNS compartments with different accessibility to immune cells and immune mediators remains unknown. Here, the authors show junctional localization of VE-cadherin in arachnoid and pia mater cells, which allows to visualize potential barrier properties of the leptomeninges in vivo.
- Josephine A. Mapunda
- Javier Pareja
- Britta Engelhardt
ArticleOpen Access20 Sep 2023 Nature Communications
Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

TSPO PET imaging is widely used to quantify microglial activation. Here, the authors show that TSPO expression increases in activated rodent but not human microglia, implying that in humans TSPO informs on microglial density rather than activation status.
- Erik Nutma
- Nurun Fancy
- David R. Owen
ArticleOpen Access28 Aug 2023 Nature Communications
CSF proteome profiling reveals biomarkers to discriminate dementia with Lewy bodies from Alzheimer´s disease

This study characterizes the CSF proteome changes underlying Dementia with Lewy Bodies (DLB) and identifies pathophysiological and diagnostic leads associated to this cause of dementia. Findings have been translated into a biomarker panel that could identify DLB patients with high accuracy across different cohorts.
- Marta del Campo
- Lisa Vermunt
- Charlotte E. Teunissen
ArticleOpen Access13 Sep 2023 Nature Communications
Effect of apolipoprotein genotype and educational attainment on cognitive function in autosomal dominant Alzheimer’s disease

PSEN1 E280A carriers develop dementia by midlife, but there is variability in disease trajectory. Cognitive decline is accelerated in E280A carriers who also have an APOE e4 allele. Educational attainment moderates the effect of APOE on cognition.
- Stephanie Langella
- N. Gil Barksdale
- Yakeel T. Quiroz
ArticleOpen Access23 Aug 2023 Nature Communications
Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice

Brain mitochondria play crucial roles that influence cognition, yet their diversity is often overlooked. This study in mice identifies distinct mitochondrial phenotypes distributed as large-scale networks, accounting for a large portion of animal-to-animal behavioural variation.
- Ayelet M. Rosenberg
- Manish Saggar
- Martin Picard
ArticleOpen Access10 Aug 2023 Nature Communications
Human OPRM1 and murine Oprm1 promoter driven viral constructs for genetic access to μ-opioidergic cell types

Tools for gaining long-term genetic access to mu-opioid receptor (MOR) neural cell types are limited. Here, the authors develop a suite of adeno-associated viral tools allowing selective genetic access to MOR cell types, and showcase their use across species.
- Gregory J. Salimando
- Sébastien Tremblay
- Gregory Corder
ArticleOpen Access13 Sep 2023 Nature Communications
Birds multiplex spectral and temporal visual information via retinal On- and Off-channels

In mammals, the retina splits visual information into functionally opposite signals, but if this applies to birds is not known. Here, the authors show a different retinal functional organization in poultry chicks, where spectral and temporal information is multiplexed.
- Marvin Seifert
- Paul A. Roberts
- Tom Baden
ArticleOpen Access31 Aug 2023 Nature Communications
Beta traveling waves in monkey frontal and parietal areas encode recent reward history

Here, the authors show that beta oscillations in the frontal and parietal lobes of monkeys propagate as traveling waves. The strength of these signals increases after rewards, suggesting a role for traveling waves in memory for recent events.
- Erfan Zabeh
- Nicholas C. Foley
- Jacqueline P. Gottlieb
ArticleOpen Access5 Sep 2023 Nature Communications
CD98hc is a target for brain delivery of biotherapeutics

New delivery platforms are needed to allow broader application of biotherapeutics for CNS diseases. Here, the authors show enhanced CNS delivery with a transport vehicle engineered to bind CD98hc, a highly expressed target at the blood-brain barrier.
- Kylie S. Chew
- Robert C. Wells
- Mihalis S. Kariolis
ArticleOpen Access19 Aug 2023 Nature Communications
Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation

Despite a wealth of knowledge on astrocytes, their contribution to cerebrovascular maturation is less known. Here, the authors identify a molecule produced by astrocytes which controls astrocyte morphology and their placement on brain blood vessels.
- Moises Freitas-Andrade
- Cesar H. Comin
- Baptiste Lacoste
ArticleOpen Access16 Aug 2023 Nature Communications
Microglial expression of CD83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis

Microglial activation is critical for coordinating the immune response during neuroinflammation. Here, the authors demonstrate that the CD83 molecule intrinsically modulates microglial activity and restrains inflammatory processes in experimental autoimmune encephalomyelitis.
- Pia Sinner
- Katrin Peckert-Maier
- Andreas B. Wild
ArticleOpen Access1 Aug 2023 Nature Communications
Glial Draper signaling triggers cross-neuron plasticity in bystander neurons after neuronal cell death in Drosophila

Neuronal death is a feature of development and neurodegeneration. Here, the authors report that ablation of Drosophila motor neurons triggers Draper-dependent signaling in glia to engage ‘cross-neuron plasticity’ in bystander neurons.
- Yupu Wang
- Ruiling Zhang
- Robert A. Carrillo
ArticleOpen Access24 Jul 2023 Nature Communications
Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution

The choroid plexus (ChP) modulates cerebrospinal fluid (CSF) composition and the blood-CSF barrier. Here the authors show that the ChP is a critical circadian component with time-of-day variations in translation, barrier, and metabolism to alter CSF composition.
- Ryann M. Fame
- Peter N. Kalugin
- Maria K. Lehtinen
ArticleOpen Access22 Jun 2023 Nature Communications
Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease

Neuroinflammatory mechanisms are implicated in Parkinson disease. Here we identify border-associated macrophages (BAMs), as essential for the α-synuclein-mediated neuroinflammatory response via class II antigen presentation, and T cell infiltration.
- A. M. Schonhoff
- D. A. Figge
- A. S. Harms
ArticleOpen Access26 Jun 2023 Nature Communications
CNS-associated macrophages shape the inflammatory response in a mouse model of Parkinson’s disease

In an alpha-synuclein (α-syn) model of Parkinson’s disease (PD), Schonhoff and colleagues have shown that central nervous system (CNS)-associated macrophages (CAMs), but not microglia, potentially orchestrate CD4⁺ T cell recruitment and mediate an α-syn-induced inflammatory makeup.
- Maximilian Frosch
- Lukas Amann
- Marco Prinz
CommentOpen Access26 Jun 2023 Nature Communications
Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer’s disease

In inflammatory arthritis, pain neurons communicate with spinal cord microglia to establish nociception. Here, the authors show that this communication is mediated by pain neurons releasing galectin-3, which activates microglia through TLR4. In a mouse model of Alzheimer’s disease, pain is attenuated because microglia lack expression of TLR4.
- George Sideris-Lampretsas
- Silvia Oggero
- Marzia Malcangio
ArticleOpen Access22 Jun 2023 Nature Communications
A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides

Parkinson’s disease (PD) is linked to environmental factors. Through quantitative epidemiology, this study ties 53 pesticides to PD. An innovative human stem cell platform revealed that 10 of these were directly toxic to human dopamine neurons.
- Kimberly C. Paul
- Richard C. Krolewski
- Beate Ritz
ArticleOpen Access16 May 2023 Nature Communications
Astrocyte-oligodendrocyte interaction regulates central nervous system regeneration

The mechanisms regulating central nervous system remyelination efficiency are poorly understood. Here, the authors show that remyelination is driven by astrocytes supporting oligodendrocyte survival, regulated by the Nrf2 and cholesterol pathways.
- Irene Molina-Gonzalez
- Rebecca K. Holloway
- Veronique E. Miron
ArticleOpen Access8 Jun 2023 Nature Communications
Disrupting the α-synuclein-ESCRT interaction with a peptide inhibitor mitigates neurodegeneration in preclinical models of Parkinson’s disease

ESCRT-III is involved in the endolysosomal system and disturbed in neurodegenerative diseases. Here the authors show that disruption of an interaction between ESCRT-III member CHMP2B and α-synuclein by a peptide inhibitor mitigates neurodegeneration in Parkinson’s disease models.
- Satra Nim
- Darren M. O’Hara
- Philip M. Kim
ArticleOpen Access19 Apr 2023 Nature Communications
Distinct astrocytic modulatory roles in sensory transmission during sleep, wakefulness, and arousal states in freely moving mice

The contribution of astrocytic Ca²⁺ signaling to the modulation of sensory transmission in different brain states remains largely unknown. Here, the authors show two types of Ca²⁺ signals in the mouse barrel cortex with distinct function in sensory transmission during sleep and arousal states.
- Fushun Wang
- Wei Wang
- Jason H. Huang
ArticleOpen Access17 Apr 2023 Nature Communications

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