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| Open AccessAgeing and brain white matter structure in 3,513 UK Biobank participants
Part of understanding ageing involves knowing how the brain’s connecting pathways change in healthy aging. Here, authors provide a detailed characterisation of data from 3513 UK Biobank participants, and show that the microstructure of these pathways becomes more similar with age.
- Simon R. Cox
- , Stuart J. Ritchie
- & Ian J. Deary
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Article
| Open AccessNeuroanatomy accounts for age-related changes in risk preferences
Tolerance for risk decreases with age, but it is not known whether this shift can be accounted for by a neurobiological marker. Here, authors show that the age-related decrease in risk tolerance is better accounted for by grey matter decreases in right posterior parietal cortex than by age per se.
- Michael A. Grubb
- , Agnieszka Tymula
- & Ifat Levy
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| Open AccessSerotonergic neuronal death and concomitant serotonin deficiency curb copulation ability of Drosophila platonic mutants
Drosophila platonic (plt) mutant males court with females but fail to copulate. Here, the authors find plt is an allele of scribblerand may disrupt courtship behaviour via developmental disruption of a subgroup of serotonergic Doublesex+ neurons in the abdominal ganglion.
- Yasemin B. Yilmazer
- , Masayuki Koganezawa
- & Daisuke Yamamoto
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Article
| Open AccessMaking brain–machine interfaces robust to future neural variability
Brain-machine interfaces (BMI) depend on algorithms to decode neural signals, but these decoders cope poorly with signal variability. Here, authors report a BMI decoder which circumvents these problems by using a large and perturbed training dataset to improve performance with variable neural signals.
- David Sussillo
- , Sergey D. Stavisky
- & Krishna V. Shenoy
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Article
| Open AccessTectal-derived interneurons contribute to phasic and tonic inhibition in the visual thalamus
The development and function of thalamic interneurons is only partially understood. Here the authors describe the unexpected mesencephalic origin of the GABAergic interneurons of the visual thalamus that provide both phasic and tonic modulation of thalamic relay neuron excitability.
- Polona Jager
- , Zhiwen Ye
- & Alessio Delogu
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Article
| Open AccessASIC1a regulates insular long-term depression and is required for the extinction of conditioned taste aversion
The acid-sensing ion channel, ASIC1a, is known to play a role in synaptic transmission and plasticity. Here, the authors demonstrate a role for ASIC1a in regulating plasticity in the insular cortex and find that extinction of conditioned taste aversion memory is disrupted in the ASIC1a knockout mice.
- Wei-Guang Li
- , Ming-Gang Liu
- & Tian-Le Xu
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Article
| Open AccessConstraints and spandrels of interareal connectomes
Whole-brain networks of long-range neuronal pathways are characterized by interdependencies between structural features. Here the author shows that module hierarchy and rich club features in these networks are structural byproducts (spandrels) of module and hub constraints, but not of wiring-cost constraints.
- Mikail Rubinov
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Article
| Open AccessPET imaging-guided chemogenetic silencing reveals a critical role of primate rostromedial caudate in reward evaluation
Processing the value of reward is thought to involve the rostromedial caudate (rmCD), but a causal demonstration is lacking in primates. Here the authors use chemogenetics and PET imaging to show that inactivation of rmCD leads to impairments in reward value judgments.
- Yuji Nagai
- , Erika Kikuchi
- & Takafumi Minamimoto
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Article
| Open AccessAtomic structure of the innexin-6 gap junction channel determined by cryo-EM
Gap junctions have critical roles in maintaining homeostasis in multicellular organisms. Here the authors present cryo-EM structures of the C. elegansinnexin-6 gap junction channel, revealing high structural similarity to human connexin 26 despite a different oligomeric number and lack of sequence similarity.
- Atsunori Oshima
- , Kazutoshi Tani
- & Yoshinori Fujiyoshi
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Article
| Open AccessTransplanted photoreceptor precursors transfer proteins to host photoreceptors by a mechanism of cytoplasmic fusion
Previous studies have used fluorescently labelled cells to demonstrate the incorporation of transplanted photoreceptor precursors into the mouse retina. Here, the authors show that fluorescent proteins are passed between the host and transplanted cells rather than migration of donor cells into the retina.
- Mandeep S. Singh
- , Jasmin Balmer
- & Robert E. MacLaren
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Article
| Open AccessStructural decoding of netrin-4 reveals a regulatory function towards mature basement membranes
Netrins are secreted guidance factors that promote axon outgrowth and orientation during nervous system development. Here the authors present structural and biological evidence that netrin-4 is not a guidance cue per se, but rather functions to modulate laminin-laminin interactions.
- Raphael Reuten
- , Trushar R. Patel
- & Manuel Koch
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Article
| Open AccessMemory consolidation reconfigures neural pathways involved in the suppression of emotional memories
As memories consolidate over time, they become resistant to change, though how this impacts the volitional suppression of memories is not known. Liu and colleagues show that, after overnight consolidation, aversive memories exhibit distributed prefrontal representations and are harder to suppress.
- Yunzhe Liu
- , Wanjun Lin
- & Shaozheng Qin
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Article
| Open AccessParvalbumin- and vasoactive intestinal polypeptide-expressing neocortical interneurons impose differential inhibition on Martinotti cells
Martinotti cells disinhibit excitatory cells in the brain cortex and play an important role in information flow. Here the authors study the role of parvalbumin and vasoactive intestinal polypeptide interneurons on the inhibition of Martinotti cells in the mouse somatosensory cortex.
- F. Walker
- , M. Möck
- & M. Witte
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Article
| Open AccessSomatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and extends C. elegans lifespan
Pluripotent stem cells are thought to require a highly active proteostatic machinery. Here, the authors show that CCT8, a subunit of the proteostatic chaperonin complex, is increased in pluripotent stem cells, and that overexpression of CCT8 in worms increases cellular proteostasis and organismal longevity.
- Alireza Noormohammadi
- , Amirabbas Khodakarami
- & David Vilchez
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Article
| Open AccessAstrocytic GABA transporter activity modulates excitatory neurotransmission
Astrocytes monitor and regulate both excitatory and inhibitory synaptic activity. Here, the authors identify a novel form of neuronal-glia communication, by which astrocytes detect rises in GABA via the GABA transporter GAT-3; this results in adenosine release that acts presynaptically to inhibit neural glutamatergic signalling.
- Kim Boddum
- , Thomas P. Jensen
- & Matthew C. Walker
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Article
| Open AccessTransduction of group I mGluR-mediated synaptic plasticity by β-arrestin2 signalling
mGluRs are known to undergo non-canonical signalling regulation, although the underlying mechanisms are unclear. Here, the authors identify a role for β-arrestin2, but not β-arrestin1, in group I mGluR-mediated plasticity at hippocampal synapses.
- Andrew G. Eng
- , Daniel A. Kelver
- & Geoffrey T. Swanson
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Article
| Open AccessMeta-adaptation in the auditory midbrain under cortical influence
Neurons in the auditory midbrain are known to modify their firing rates in response to changes in sound intensity. Here the authors show that in guinea pigs, such modifications occur faster when neurons re-encounter the same environment, a phenomenon they term meta-adaptation.
- Benjamin L. Robinson
- , Nicol S. Harper
- & David McAlpine
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Article
| Open AccessGlobal gain modulation generates time-dependent urgency during perceptual choice in humans
Decision-making balances the benefits of additional information with the cost of time, but it is unclear whether humans adjust this balance within individual decisions. Here, authors show that we do make such adjustments to suit contextual demands and suggest that these are driven by modulation of neural gain.
- Peter R. Murphy
- , Evert Boonstra
- & Sander Nieuwenhuis
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Article
| Open AccessFunctional implications of orientation maps in primary visual cortex
Stimulus orientation in the primary visual cortex of primates and carnivores is mapped into a geometrical mosaic but the functional implications of these maps remain debated. Here the authors reveal an association between the structure of cortical orientation maps in cats, and the functions of local cortical circuits in processing patterns and contours.
- Erin Koch
- , Jianzhong Jin
- & Qasim Zaidi
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Article
| Open AccessVCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination
The vascular cell adhesion molecule VCAM1 plays a role in the immune system but is also expressed in oligodendrocytes. Here, the authors find VCAM1 interacts with neuronal α4 integrin to regulate oligodendrocyte differentiation and thereby myelination, an effect mediated by downstream CD69 signalling.
- Yuki Miyamoto
- , Tomohiro Torii
- & Junji Yamauchi
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Article
| Open AccessDeep phenotyping unveils hidden traits and genetic relations in subtle mutants
Experimenter scoring of cellular imaging data can be biased. This study describes an automated and unbiased multidimensional phenotyping method that relies on machine learning and complex feature computation of imaging data, and identifies weak alleles affecting synapse morphology in live C. elegans.
- Adriana San-Miguel
- , Peri T. Kurshan
- & Hang Lu
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Article
| Open AccessDefective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease
Accumulated damage to mitochondrial DNA (mtDNA) occurs during the ageing process and neurodegenerative disease. Here, the authors show that mtDNA copy number increases in an age-dependent manner in substantia nigra of healthy individuals, but not in individuals with Parkinson disease.
- Christian Dölle
- , Irene Flønes
- & Charalampos Tzoulis
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Article
| Open AccessA radial map of multi-whisker correlation selectivity in the rat barrel cortex
Barrel cortex contains a functional map of whiskers but how neuronal activity maps multi-whisker inputs has not been studied. Here the authors show that while uncorrelated multi-whisker stimuli activate barrel neurons, correlated multi-whisker inputs activate neurons in a ring at the barrel-septa boundary
- Luc Estebanez
- , Julien Bertherat
- & Jean- François Léger
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Article
| Open AccessCerebral vascular amyloid seeds drive amyloid β-protein fibril assembly with a distinct anti-parallel structure
Cerebrovascular accumulation of Aβ is a common feature of Alzheimer’s disease, though it is unclear whether mutant vascular amyloid is capable of Aβ seeding. Here, the authors show microvascular amyloid seeds are capable of driving wild-type Aβ to assemble into distinctive anti-parallel fibrillary structures.
- Feng Xu
- , Ziao Fu
- & William E. Van Nostrand
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Article
| Open AccessAn elastic element in the protocadherin-15 tip link of the inner ear
Tip-link filaments convey force to activate hair cells, important sensory receptors. Here the authors solve a partial structure of human protocadherin-15, a tip-link component with an unusual Ca2+–free linker that bends and is predicted to confer flexibility to this filament during inner-ear mechanotransduction.
- Raul Araya-Secchi
- , Brandon L. Neel
- & Marcos Sotomayor
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Article
| Open AccessSpatially precise visual gain control mediated by a cholinergic circuit in the midbrain attention network
Attention and gaze impact the spatial responsiveness of neurons in the optic tectum. Here the authors elucidate the mechanism by which cholinergic inputs affect receptive field properties of tectal neurons in a spatially precise manner in barn owls.
- Ali Asadollahi
- & Eric I. Knudsen
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Article
| Open AccessCl-out is a novel cooperative optogenetic tool for extruding chloride from neurons
Chloride regulation is important for setting GABAergic reversal potential, though tools to manipulate chloride levels are limited. Here, the authors combine Archaerhodopsin with a chloride channel opsin to generate an optogenetic chloride extrusion strategy, ‘Cl-out’, which they demonstrate in hippocampal slices.
- Hannah Alfonsa
- , Jeremy H. Lakey
- & Andrew J. Trevelyan
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Article
| Open AccessDendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells
Back-propagating action potentials (bAP) and NMDA dendritic spikes have both been linked to long-term plasticity (LTP) induction, though it is unclear which factors are essential. Here, using electrophysiology and Ca2+imaging, the authors find NMDA spikes are a key initiator of LTP, and that bAP contribution occurs via NMDA spike triggering.
- Federico Brandalise
- , Stefano Carta
- & Urs Gerber
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Article
| Open AccessMyelinosome formation represents an early stage of oligodendrocyte damage in multiple sclerosis and its animal model
Oligodendrocyte damage is a key component of demyelinating diseases. Here, the authors use in vivolight and correlated electron microscopy in EAE mouse models, and find early damage occurs at the myelin sheath before spreading to the oligodendrocyte cell body.
- Elisa Romanelli
- , Doron Merkler
- & Martin Kerschensteiner
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Article
| Open AccessFast ensemble representations for abstract visual impressions
Perceiving objects as lifelike is an inferential process but whether it occurs quickly and how it applies to groups of objects is not well understood. Here the authors show that observers’ percepts of crowd lifelikeness are fast and represent the average of the individual objects comprising that crowd.
- Allison Yamanashi Leib
- , Anna Kosovicheva
- & David Whitney
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Article
| Open AccessLack of Diaph3 relaxes the spindle checkpoint causing the loss of neural progenitors
Molecular mechanisms that control the division of neural progenitor cells are only partially understood. Here the authors show that Diaph3 is critical for spindle checkpoint activity in cortical progenitor cells as the loss of Diaph3 leads to apoptosis of progenitor cells and eventually results in microcephaly in mice.
- Devid Damiani
- , André M. Goffinet
- & Fadel Tissir
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Article
| Open AccessHyperconnectivity of prefrontal cortex to amygdala projections in a mouse model of macrocephaly/autism syndrome
Dysregulation of mTOR signaling has been implicated in autism spectrum disorders. Here authors show that hyperconnectivity and hyperactivity of the mPFC–BLA circuitry inPten+/−mice underlies their social impairments, and that reducing mTORC1 signaling during early postnatal development rescues these deficits.
- Wen-Chin Huang
- , Youjun Chen
- & Damon T. Page
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Article
| Open AccessLong-term coding of personal and universal associations underlying the memory web in the human brain
Neurons in the medial temporal lobe change their firing patterns as people learn to pair items together, yet it is unclear if this pairing lasts. Here, authors find that single medial temporal lobe neurons in humans tend to respond similarly to items that are closely conceptually related.
- Emanuela De Falco
- , Matias J. Ison
- & Rodrigo Quian Quiroga
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Article
| Open AccessMultidimensional heritability analysis of neuroanatomical shape
Neuroanatomical shape measurements are multidimensional geometric descriptions of brain structure. This study develops multivariate heritability analysis methods and examines structural brain MRI scans and genetic data to estimate the heritability of neuroanatomical shape.
- Tian Ge
- , Martin Reuter
- & Mert R. Sabuncu
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Article
| Open AccessRegulation of persistent sodium currents by glycogen synthase kinase 3 encodes daily rhythms of neuronal excitability
It is not clear how circadian biochemical cascades are encoded into neural electrical signals. Here, using a combination of electrophysiology and modelling approaches in mice, the authors show activation of glycogen synthase kinase 3 modulates neural activity in the suprachiasmatic nuclei via regulation of the persistent sodium current, INaP.
- Jodi R. Paul
- , Daniel DeWoskin
- & Karen L. Gamble
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Article
| Open AccessShifting transcriptional machinery is required for long-term memory maintenance and modification in Drosophila mushroom bodies
Transcriptional regulation is necessary for maintaining long-term memories (LTM) but the mechanistic details are not completely defined. Here the authors identify transcriptional machinery and histone modifiers required for LTM maintenance inDrosophilaand show that transcriptional regulation for LTM maintenance is distinct from that for LTM formation.
- Yukinori Hirano
- , Kunio Ihara
- & Minoru Saitoe
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Article
| Open AccessMapping synaptic glutamate transporter dysfunction in vivo to regions surrounding Aβ plaques by iGluSnFR two-photon imaging
In Alzheimer’s disease (AD), neural hyperactivity has been shown to occur in the regions surrounding Aβ plaques. Here, the authors use in vivotwo-photon imaging in mouse models of AD and report abnormal glutamate dynamics in the vicinity of plaques which can be partially restored via GLT-1 upregulation through Ceftriaxone treatment.
- J. K. Hefendehl
- , J. LeDue
- & B. A. MacVicar
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Article
| Open AccessCoupled binding mechanism of three sodium ions and aspartate in the glutamate transporter homologue GltTk
In neurons and glia, glutamate transporters catalyse the reuptake of this neurotransmitter by coupling it with cation transport. Here the authors combine X-ray crystallography and molecular dynamics simulations of the archeal glutamate transporter GltTkto get insight into the coupled transport mechanism.
- Albert Guskov
- , Sonja Jensen
- & Dirk Jan Slotboom
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Article
| Open AccessSensing of HSV-1 by the cGAS–STING pathway in microglia orchestrates antiviral defence in the CNS
The cGAS–STING pathway is an important immune defence pathway against viral infection, including HSV-1. Here the authors use an HSV-1 encephalitis model and show microglia are the main producers of type 1 interferons that induce antiviral activity in neurons and prime the TLR3-interferon pathway in astrocytes.
- Line S. Reinert
- , Katarína Lopušná
- & Søren R. Paludan
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Article
| Open AccessNeural correlates of working memory development in adolescent primates
Working memory is known to improve through adolescence into adulthood, yet the associated changes in neuronal activity are not well understood. Zhou and colleagues report increased delay period activity correlated with changes in performance on working memory tasks in monkeys as they transition into adulthood.
- Xin Zhou
- , Dantong Zhu
- & Christos Constantinidis
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Article
| Open AccessDecrease of SYNGAP1 in GABAergic cells impairs inhibitory synapse connectivity, synaptic inhibition and cognitive function
Glutamatergic signalling regulation by Syngap1 has been linked to intellectual disabilities. Here, the authors find Syngap1 also regulates cortical GABAergic synaptic signalling development and that this reduced inhibitory signalling contributes to cognitive deficits in a mouse model.
- Martin H. Berryer
- , Bidisha Chattopadhyaya
- & Graziella Di Cristo
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Article
| Open AccessPupil fluctuations track rapid changes in adrenergic and cholinergic activity in cortex
In addition to light intensity, changes in pupil diameter are correlated with mental effort, attention and levels of arousal. Reimer et al. report that across behavioural states, fluctuations in pupil diameter are highly correlated with activity of noradrenergic and cholinergic projection neurons.
- Jacob Reimer
- , Matthew J McGinley
- & Andreas S Tolias
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Article
| Open AccessPromotion of behavior and neuronal function by reactive oxygen species in C. elegans
The deleterious role of reactive oxygen species has been widely reported in the nervous system. Here the authors report that surprisingly, low doses of H2O2 in fact enhances sensory neuron function and promotes sensory behaviors in C. elegans.
- Guang Li
- , Jianke Gong
- & X. Z. Shawn Xu
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Article
| Open AccessRandom synaptic feedback weights support error backpropagation for deep learning
Multi-layered neural architectures that implement learning require elaborate mechanisms for symmetric backpropagation of errors that are biologically implausible. Here the authors propose a simple resolution to this problem of blame assignment that works even with feedback using random synaptic weights.
- Timothy P. Lillicrap
- , Daniel Cownden
- & Colin J. Akerman
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Article
| Open AccessSeveral posttranslational modifications act in concert to regulate gephyrin scaffolding and GABAergic transmission
Gephyrin is a cytoplasmic scaffolding protein that selectively forms postsynaptic scaffolds at GABAergic and glycinergic synapses. Here the authors characterize regulatory mechanisms determining gephyrin scaffolding and GABAA receptor synaptic transmission that involve acetylation, SUMOylation and phosphorylation.
- Himanish Ghosh
- , Luca Auguadri
- & Shiva K. Tyagarajan
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Article
| Open AccessBasal forebrain degeneration precedes and predicts the cortical spread of Alzheimer’s pathology
Whether Alzheimer’s disease originates in basal forebrain or entorhinal cortex remains highly debated. Here the authors use structural magnetic resonance data from a longitudinal sample of participants stratified by cerebrospinal biomarker and clinical diagnosis to show that tissue volume changes appear earlier in the basal forebrain than in the entorhinal cortex.
- Taylor W. Schmitz
- , R. Nathan Spreng
- & Ansgar J. Furst
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Article
| Open AccessIntegration and segregation of large-scale brain networks during short-term task automatization
Humans can quickly learn to efficiently execute tasks yet how the brain activity is dynamically reconfigured during this process remains unknown. Here the authors demonstrate that large-scale functional brain networks are reorganized flexibly to support rapid task automation.
- Holger Mohr
- , Uta Wolfensteller
- & Hannes Ruge
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Article
| Open AccessSocial support reduces stress hormone levels in wild chimpanzees across stressful events and everyday affiliations
The stress-reducing effects of social bonds have been hypothesized to accrue either during stressful events or across daily affiliations. Here, Wittiget al. show that the presence of social partners reduces levels of stress hormones in wild chimpanzees beyond stressful contexts, supporting the latter hypothesis.
- Roman M. Wittig
- , Catherine Crockford
- & Klaus Zuberbühler
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Article
| Open AccessSpontaneous emergence of fast attractor dynamics in a model of developing primary visual cortex
Sensory cortices represent stimuli through joint activity of competing neuronal assemblies. Here the authors show that a model of visual cortex with plastic feedforward and recurrent synapses, exposed to natural images, spontaneously develops attractor dynamics between groups of similarly tuned neurons.
- Thomas Miconi
- , Jeffrey L. McKinstry
- & Gerald M. Edelman
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