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| Open AccessStereotypic wheel running decreases cortical activity in mice
Sleep need is thought to accumulate gradually over waking periods and is associated with changes in neuronal activity. Here the authors show that in mice cortical firing rates increase between the beginning and end of wakefulness periods but this increase is not seen in waking periods with voluntary stereotypic wheel running.
- Simon P. Fisher
- , Nanyi Cui
- & Vladyslav V. Vyazovskiy
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Article
| Open AccessPurification of functional human ES and iPSC-derived midbrain dopaminergic progenitors using LRTM1
Midbrain dopaminergic neurons generated from stem cells show promise for the treatment of Parkinson’s disease. Here, the authors use the cell surface marker, LRTM1, to enrich the midbrain dopaminergic progenitors and show improved motor function/cell survival when grafted into rat/monkey brains, respectively.
- Bumpei Samata
- , Daisuke Doi
- & Jun Takahashi
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Article
| Open AccessGlucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia
Neuropathic pain hypersensitivity is known to undergo diurnal variations, although the underlying mechanisms are not clear. Using a sciatic nerve-injury mouse model, the authors find such diurnal changes are mediated by glucocorticoid induced enhancement of ATP release from astrocytes via pannexin-1 hemichannels.
- Satoru Koyanagi
- , Naoki Kusunose
- & Shigehiro Ohdo
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Article
| Open AccessKCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting
Specificity of inhibitors of voltage-gated ion channels is crucial for their use as therapeutics. Here, the authors show that adamantane derivatives interact with a specific binding site on fenestrations that only become available when accessory subunits are bound to the channel.
- Eva Wrobel
- , Ina Rothenberg
- & Guiscard Seebohm
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Article
| Open AccessNicotinamide is an endogenous agonist for a C. elegans TRPV OSM-9 and OCR-4 channel
TRPV are cation channels activated by physical and chemical stimuli. Here the authors show that nicotinamide is a soluble, endogenous agonist for orthologous TRPV channels fromC. elegans and Drosophila, unveiling a metabolic-based regulation for TRPV channel activity.
- Awani Upadhyay
- , Aditya Pisupati
- & Wendy Hanna-Rose
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| Open AccessInhibition of TRPV1 channels by a naturally occurring omega-9 fatty acid reduces pain and itch
TRPV1 channels are known to mediate pathological pain and itch. Here, the authors find a naturally occurring fatty acid, oleic acid, acts as a TRPV1 antagonist and can modulate capsaicin and histamine-mediated pain and itch response in mouse models.
- Sara L. Morales-Lázaro
- , Itzel Llorente
- & Tamara Rosenbaum
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Article
| Open AccessSensory feedback synchronizes motor and sensory neuronal networks in the neonatal rat spinal cord
Spontaneous movements are important for mammalian development but how network activity underlies the generation of these actions remains unclear. Here the authors show that both spontaneous twitches and complex movements enable correlated activity in motor and sensory networks of the rat spinal cord in vivo, and that sensory feedback is instrumental in this synchronization.
- Ana R. Inácio
- , Azat Nasretdinov
- & Roustem Khazipov
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Article
| Open AccessStriatal prediction errors support dynamic control of declarative memory decisions
The human brain can efficiently retrieve information from long-term memory and use it to guide action but how the brain selects the most useful information in each case is unclear. Here the authors show that reinforcement learning mechanisms, based on expected value and prediction error fMRI signals in striatum, play a role in memory control processes guiding behavior.
- Jason M. Scimeca
- , Perri L. Katzman
- & David Badre
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Article
| Open AccessMotor cortex activity predicts response alternation during sensorimotor decisions
The motor cortex executes responses based on sensory choices, but it is unknown whether it also impacts response selection. Here, Pape and Siegel show that motor cortex activity present before decision making predicts responses and that this activity is influenced by previous button-presses.
- Anna-Antonia Pape
- & Markus Siegel
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Article
| Open AccessSocial learning strategies modify the effect of network structure on group performance
Previous studies have disagreed over whether efficient or inefficient network structures should be more effective in promoting group performance. Here, Barkoczi and Galesic demonstrate that which structure is superior depends on the social learning strategy used by individuals in the network.
- Daniel Barkoczi
- & Mirta Galesic
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Article
| Open AccessAnalogue modulation of back-propagating action potentials enables dendritic hybrid signalling
‘Analogue’ modulation by somatic membrane potentials can modify ‘digital’ axonal action potentials. Here, the authors show that analogue modulation can occur in back-propagating dendritic action potentials and calcium signals, leading to signal enhancement or attenuation in a location-dependent manner.
- János Brunner
- & János Szabadics
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Article
| Open AccessProkineticin-2 upregulation during neuronal injury mediates a compensatory protective response against dopaminergic neuronal degeneration
Prokineticin-2 (PK2) is a secreted protein involved in a number of physiological functions. Here, the authors find that PK2 expression increases in surviving DA neurons from Parkinson's disease patients, and show it protects against dopaminergic degeneration in PD mouse models.
- Richard Gordon
- , Matthew L. Neal
- & Arthi Kanthasamy
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Article
| Open AccessDivergent effects of central melanocortin signalling on fat and sucrose preference in humans
Hypothalamic melanocortin-4-receptors (MC4R) regulate food preference in rodents, but their role in humans is unclear. Here, the authors perform food preference and liking tests in humans with MC4R mutations and find that they prefer fatty food more, but sweet food less, than people without MC4R mutations.
- Agatha A. van der Klaauw
- , Julia M. Keogh
- & I. Sadaf Farooqi
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Article
| Open AccessRetinal transplantation of photoreceptors results in donor–host cytoplasmic exchange
Integration of transplanted photoreceptors into the host retina has been assumed as the underlying mechanism for vision improvement in pre-clinical studies. Here, the authors show that the majority of transplanted photoreceptors do not structurally integrate but exchange intercellular material with host cells.
- Tiago Santos-Ferreira
- , Sílvia Llonch
- & Marius Ader
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| Open AccessDonor and host photoreceptors engage in material transfer following transplantation of post-mitotic photoreceptor precursors
Transplantation of healthy photoreceptor cells has been shown to rescue blindness. Here, the authors show that rather than donor cells integrating into the host retina, the predominant mechanism underlying this rescue involves exchange of cytoplasmic material between donor and host cells in vivo.
- R. A. Pearson
- , A. Gonzalez-Cordero
- & R. R. Ali
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| Open AccessAgeing increases reliance on sensorimotor prediction through structural and functional differences in frontostriatal circuits
Decline in sensorimotor skills with age may be due to an overreliance on the prediction of the sensory consequences of one’s actions. Here the authors show that sensorimotor attenuation increases with age, and that this is associated with structural and functional changes in frontostriatal circuits.
- Noham Wolpe
- , James N. Ingram
- & James B. Rowe
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Article
| Open AccessLocalized force application reveals mechanically sensitive domains of Piezo1
Piezo ion channels transduce mechanical forces into biological signals. Here, the authors use magnetic tweezers to pull specific regions of Piezo1, identifying mechanically sensitive domains that are essential for channel activation and inactivation.
- Jason Wu
- , Raman Goyal
- & Jörg Grandl
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Article
| Open AccessOrganization of olfactory centres in the malaria mosquito Anopheles gambiae
Mosquitoes use olfactory cues to locate their host. Here, Riabinina et al. use genetic labelling of olfactory receptor neurons in the malaria vector Anopheles gambiaeto show that these neurons project to the antennal lobe, a known insect olfactory centre, and the subesophageal zone, a region previously linked to gustatory processing.
- Olena Riabinina
- , Darya Task
- & Christopher J. Potter
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Article
| Open AccessA plasma membrane microdomain compartmentalizes ephrin-generated cAMP signals to prune developing retinal axon arbors
It is unclear what role cholesterol-enriched domains of the plasma membrane play in mediating the development of neuronal circuits. Here, the authors show that such domains localize ephrin-A-induced cAMP signals, causing the pruning of retinal ganglion cell axons.
- Stefania Averaimo
- , Ahlem Assali
- & Xavier Nicol
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Article
| Open AccessSCOP/PHLPP1β mediates circadian regulation of long-term recognition memory
Learning and memory are subject to circadian variation, though the molecular mechanisms behind this are unclear. Here, the authors show SCOP, a regulator of hippocampal memory, undergoes circadian changes in CA1 membrane raft dynamics and contributes to time-dependent changes in long-term memory.
- Kimiko Shimizu
- , Yodai Kobayashi
- & Yoshitaka Fukada
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Article
| Open AccessFlux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and TrkB
Signalling endosomes are known to be essential for neuronal survival. Here the authors show that, in cultured hippocampal neurons and live Drosophilalarval motor neurons, neuronal activity increases the retrograde flux of signalling endosomes, and this coupling depends on TrkB activation.
- Tong Wang
- , Sally Martin
- & Frédéric A. Meunier
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Article
| Open AccessFoxO1 in dopaminergic neurons regulates energy homeostasis and targets tyrosine hydroxylase
Dopaminergic neurons are important for regulating energy homeostasis. Here, the authors show the transcription factor FoxO1 negatively regulates tyrosine hydroxylase expression in midbrain dopaminergic neurons, and plays an important role in regulation of glucose homeostasis, energy expenditure, and resistance to diet-induced obesity.
- Khanh V. Doan
- , Ann W. Kinyua
- & Ki Woo Kim
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Article
| Open AccessTransition metal ion FRET uncovers K+ regulation of a neurotransmitter/sodium symporter
The neurotransmitter transporter SERT counter transport K+ to transport serotonin. Here the authors show that the activity of the prokaryotic orthologue LeuT is also modulated by this cation, suggesting a general regulatory role for K+on neutrotrasmitter:sodium symporters function.
- Christian B. Billesbølle
- , Jonas S. Mortensen
- & Claus J. Loland
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Article
| Open AccessMolecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells
Kainate receptors are selectively found at CA3-mossy fibre synapses, although the mechanisms regulating this compartmentalisation have yet to be determined. Here, the authors find KAR segregation is dependent on the amount of GluK2a protein and an interaction between the GluK2 C-terminal domain and N-cadherin.
- Sabine Fièvre
- , Mario Carta
- & Christophe Mulle
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Article
| Open AccessA cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication
Immune system participates in the development of high blood pressure. Here the authors show that cholinergic-sympathetic pathway mediated by the α7nAChR receptor and the activation of splenic T cells prime immunity during hypertension and that selective splenic denervation protects against the onset of hypertension in mice.
- Daniela Carnevale
- , Marialuisa Perrotta
- & Giuseppe Lembo
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Article
| Open AccessFHF-independent conduction of action potentials along the leak-resistant cerebellar granule cell axon
FHFs are known to regulate voltage-gated sodium channels (NaVs). Here, the authors compare the role of FHFs in cerebellar granule cell propagation, and find NaVs in the distal axon function independently of FHFs, allowing for faster inactivation rates and reducing energy demands during repetitive spiking.
- Katarzyna Dover
- , Christopher Marra
- & Mitchell Goldfarb
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Article
| Open AccessFMRP regulates an ethanol-dependent shift in GABABR function and expression with rapid antidepressant properties
Alcohol is thought to lead to neuroadaptive changes, although the underlying molecular mechanisms are unclear. Here, the authors find ethanol treatment alters GABAB-receptor expression via fragile-X mental retardation protein in mice, leading to antidepressant-like behaviours.
- Sarah A. Wolfe
- , Emily R. Workman
- & Kimberly F. Raab-Graham
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Article
| Open AccessTransport of a kinesin-cargo pair along microtubules into dendritic spines undergoing synaptic plasticity
Transport of cargo into dendritic spines is required for synaptic plasticity. McVicker et al.describe a method of activity-dependent transport of a kinesin KIF1A and its cargo synaptotagmin-IV along microtubules that are transiently polymerized into dendritic spines.
- Derrick P. McVicker
- , Adam M. Awe
- & Erik W. Dent
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Article
| Open AccessRepresentational changes of latent strategies in rat medial prefrontal cortex precede changes in behaviour
The medial prefrontal cortex (mPFC) is involved in changing behavioural strategies. Recording neural ensembles in rats, Powell and Redish find that the requirement for those changes is represented in mPFC before they manifest behaviourally, both in tasks that externally force a change and in tasks with self-determined change.
- Nathaniel James Powell
- & A. David Redish
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Article
| Open AccessSpatiotemporal dynamics of lesion-induced axonal sprouting and its relation to functional architecture of the cerebellum
Neurodegenerative lesions induce sprouting from surviving axons, but the patterns of re-innervation of these collaterals in relation to existing functional networks remains unclear. Here the authors performed long term in vivoimaging in mice, of sprouts from cerebellar climbing fibers after a lesion, and describe the patterns of connectivity relative to functionally active zones.
- Matasha Dhar
- , Joshua M. Brenner
- & Hiroshi Nishiyama
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Article
| Open AccessA dendritic disinhibitory circuit mechanism for pathway-specific gating
Cortical circuits receive simultaneous inputs from multiple pathways and are able to flexibly select the appropriate inputs for processing. Here the authors propose a network model in which dendritic branch-specific disinhibition established through synaptic plasticity achieves pathway-specific gating.
- Guangyu Robert Yang
- , John D. Murray
- & Xiao-Jing Wang
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Article
| Open AccessDelayed glial clearance of degenerating axons in aged Drosophila is due to reduced PI3K/Draper activity
Glial engulfment declines with age, but the mechanism is unclear. Here authors show that in the Drosophilaolfactory system, glial phagocytosis of injury-induced degenerating axons decreases with age due to reduced PI3K/Draper activity, and restoring Draper in aged glia rescues such defects.
- Maria D. Purice
- , Sean D. Speese
- & Mary A. Logan
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Article
| Open AccessOptogenetically enhanced pituitary corticotroph cell activity post-stress onset causes rapid organizing effects on behaviour
Behavioural adaptations in response to stress are thought to be regulated by rapid neurotransmitter action, followed by slower hormonal signalling. Here, using optogenetic approaches, the authors find corticotroph cell populations are capable of rapidly modulating avoidance behaviours immediately after the onset of stress.
- Rodrigo J. De Marco
- , Theresa Thiemann
- & Soojin Ryu
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Article
| Open AccessStructural basis of synaptic vesicle assembly promoted by α-synuclein
α-synuclein, a protein associated to Parkinson's disease, is involved in synaptic vesicle interaction and assembly. Here, the authors use NMR spectroscopy and super-resolution microscopy to unveil the nature and molecular mechanism of α-synuclein-mediated synaptic vesicle clustering.
- Giuliana Fusco
- , Tillmann Pape
- & Alfonso De Simone
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Article
| Open AccessMechanosensory neurons control sweet sensing in Drosophila
How different sensory modalities interact to control feeding is poorly understood. Here, authors show that in Drosophila, activation of labellar mechanosensory neurons causes inhibition of sweet-sensing gustatory receptor neurons, as a result, Drosophilaprefer soft food at the expense of sweetness.
- Yong Taek Jeong
- , Soo Min Oh
- & Seok Jun Moon
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Article
| Open AccessCold sensitivity of TRPA1 is unveiled by the prolyl hydroxylation blockade-induced sensitization to ROS
The transient receptor potential ankyrin 1 (TRPA1) is a cation channel that is involved in nociceptive pain sensing. Here, the authors show that hydroxylation of a proline in the N terminus of TRPA1 renders it sensitive to reactive oxygen species resulting from noxious cold.
- Takahito Miyake
- , Saki Nakamura
- & Shuji Kaneko
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Article
| Open AccessNeurons in the primate dorsal striatum signal the uncertainty of object–reward associations
The dorsal striatum (DS) is a brain region that is thought to aim actions at certain or known rewards. Here, the authors show that an internal-capsule bordering region of the primate DS signals the uncertainty of object-reward associations, suggesting a novel role for the DS in behavior under uncertainty.
- J. Kael White
- & Ilya E. Monosov
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Article
| Open AccessA dynamic code for economic object valuation in prefrontal cortex neurons
Economic decisions are based on perceived reward value but it is unclear how individual neurons encode value estimates as input for decision mechanisms. Here authors show that dorsolateral prefrontal cortex uses a dynamic value code based on object-specific valuations by single neurons.
- Ken-Ichiro Tsutsui
- , Fabian Grabenhorst
- & Wolfram Schultz
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Article
| Open AccessCentral relay of bitter taste to the protocerebrum by peptidergic interneurons in the Drosophila brain
Bitter taste evokes aversive behaviour in animals, but little is known about the central nervous system mechanisms that convey this taste modality. Hückesfeld et al. identify a set of second order neurons in Drosophilathat contain hugin neuropeptide and are responsible for conveying bitter taste to the protocerebrum.
- Sebastian Hückesfeld
- , Marc Peters
- & Michael J. Pankratz
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Article
| Open AccessStructural insights into the interaction and disease mechanism of neurodegenerative disease-associated optineurin and TBK1 proteins
Mutations in optineurin that cause defects in the interaction with TBK1 are associated with neurodegenerative diseases. Here, the authors report the structure of this complex, and outline a general binding mode for these proteins.
- Faxiang Li
- , Xingqiao Xie
- & Lifeng Pan
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Article
| Open AccessLocal and thalamic origins of correlated ongoing and sensory-evoked cortical activities
Sensory cortices receive input from cortical cells and the thalamus, yet it is unknown how these inputs interact to generate synchronous activity. Here authors show that unlike cortical inputs, thalamic inputs are asynchronous, suggesting that cortical synchronization is due to intracortical coupling.
- Katayun Cohen-Kashi Malina
- , Boaz Mohar
- & Ilan Lampl
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Article
| Open AccessEfficient sensory cortical coding optimizes pursuit eye movements
Efficient coding suggests that adapting gain to match the varying stimulus statistics should help in optimizing behaviour. Here the authors show that adaptation in motion sensitive neurons maximizes information and improves movement accuracy in pursuit eye movements.
- Bing Liu
- , Matthew V. Macellaio
- & Leslie C. Osborne
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Article
| Open AccessPten and EphB4 regulate the establishment of perisomatic inhibition in mouse visual cortex
Fast spiking interneurons provide perisomatic inhibition in the cortex. Here, Baohan et al. show the failure to develop perisomatic inhibition in heterozygous PTENnull mutant mouse and the underlying mechanism to EphB4 reduction in an experience-dependent manner.
- Amy Baohan
- , Taruna Ikrar
- & Joshua T. Trachtenberg
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Article
| Open AccessLayer-specific cholinergic control of human and mouse cortical synaptic plasticity
Nicotinic acetylcholine receptors (nAChRs) are differentially expressed across cortical layers, yet it is unclear whether they show layer-specific effects on synaptic plasticity in the prefrontal cortex. Here, the authors compare nAChRs across L6 and L2/3 in human and mouse cortex and find they mediate opposite effects on synaptic plasticity.
- Matthijs B. Verhoog
- , Joshua Obermayer
- & Huibert D. Mansvelder
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Article
| Open AccessObservational learning computations in neurons of the human anterior cingulate cortex
Humans can learn alone or by watching others, strategies which may depend on similar or different neural networks. This study shows that people watching other players in a card game used computations in neurons of their rostral anterior cingulate cortex to learn through observation.
- Michael R. Hill
- , Erie D. Boorman
- & Itzhak Fried
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Article
| Open AccessLongitudinal assessment of neuronal 3D genomes in mouse prefrontal cortex
Chromosome conformation is a dynamic process, especially in brain. Here, Mitchell and colleagues devise a method they call NeuroDam that can prospectively tag chromosome conformation in the mouse brain in vivo, and longitudinally assess long range chromosome looping weeks and months later.
- Amanda C. Mitchell
- , Behnam Javidfar
- & Schahram Akbarian
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Article
| Open AccessStereotyped initiation of retinal waves by bipolar cells via presynaptic NMDA autoreceptors
Retinal waves are important for visual system development. However, the mechanism involved in their generation remains largely unknown. Here using in vivotwo-photon imaging the authors identify the presence of retinal waves in zebrafish larvae and find that they are initiated at bipolar cells via presynaptic NMDARs.
- Rong-wei Zhang
- , Xiao-quan Li
- & Jiu-lin Du
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Article
| Open AccessDysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice
Mutations in SHANK2 are associated with autism spectrum disorders (ASD). Here, Peter et al. show that selective loss of Shank2in Purkinje cells of the mouse cerebellum leads to deficits in plasticity, motor behaviour, and a social behaviour phenotype similar to that seen in ASD.
- Saša Peter
- , Michiel M. ten Brinke
- & Chris I. De Zeeuw
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Article
| Open AccessTemporal asymmetries in auditory coding and perception reflect multi-layered nonlinearities
In humans, sounds that increase in intensity over time (up-ramp) are perceived as louder than down-ramping sounds. Here the authors show that in mice this bias also exists and is reflected in the complex nonlinearities of auditory cortex activity.
- Thomas Deneux
- , Alexandre Kempf
- & Brice Bathellier
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