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| Open AccessTolerance to ambiguous uncertainty predicts prosocial behavior
Ambiguous uncertainty refers to situations where the likelihood of specific outcomes are not known. Here, the authors show that people tolerant to ambiguous uncertainty are more likely to make costly decisions to cooperate with or trust others.
- Marc-Lluís Vives
- & Oriel FeldmanHall
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Article
| Open Accessα-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson’s disease
How toxic aggregated forms of α-synuclein lead to neurodegeneration is unclear. Here authors use biophysical and cellular imaging methods to show that specific oligomers of α-synuclein exert effects on mitochondria to induce opening of the permeability transition pore, leading to cell death in Parkinson’s disease.
- Marthe H. R. Ludtmann
- , Plamena R. Angelova
- & Sonia Gandhi
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Article
| Open AccessSpatio-temporal relays control layer identity of direction-selective neuron subtypes in Drosophila
Direction-selective T4/T5 neurons show layer-specific projections in the fly visual circuit. Examining the mechanisms behind their development, the authors found that a relay of Wnt and Bmp signaling across neuroepithelial domains and transcription factor interactions specify T4/T5 subtype identity.
- Holger Apitz
- & Iris Salecker
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| Open AccessPostsynaptic RIM1 modulates synaptic function by facilitating membrane delivery of recycling NMDARs in hippocampal neurons
Rab3-interacting molecules (RIMs) are a key component of the presynaptic active zone that regulate neurotransmitter release. Here, the authors show that RIM1 also has postsynaptic function to organize NMDA receptors and synaptic response.
- Jiejie Wang
- , Xinyou Lv
- & Shuang Qiu
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Article
| Open AccessTop-down feedback controls spatial summation and response amplitude in primate visual cortex
Feedback modulation of V1 is implicated in functions such as attention yet the precise neural mechanisms are not known. Here the authors report that optogenetic inactivation of V2 projections leads to modulation of V1 receptive field properties such as size, surround suppression and response amplitude.
- Lauri Nurminen
- , Sam Merlin
- & Alessandra Angelucci
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Article
| Open AccessFinding influential nodes for integration in brain networks using optimal percolation theory
Complex networks can be used to model brain networks. Here the authors identify the essential nodes in a model of a brain network and then validate these predictions by means of in vivo pharmacogenetic interventions. They find that the nucleus accumbens is a central region for brain integration.
- Gino Del Ferraro
- , Andrea Moreno
- & Hernán A. Makse
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Article
| Open AccessIdentifying gene targets for brain-related traits using transcriptomic and methylomic data from blood
To comprehend the genetic regulatory mechanisms underlying brain-related traits in humans, Qi et al. estimate the correlation of expression and DNA methylation QTL effects in cis between blood and brain and show that using blood eQTL/mQTL data of large sample size can increase power in gene discovery for brain-related traits and diseases.
- Ting Qi
- , Yang Wu
- & Jian Yang
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Article
| Open AccessVariations in Dysbindin-1 are associated with cognitive response to antipsychotic drug treatment
Patients with schizophrenia show varied response to antipsychotics. Here, the authors demonstrate in patients under antipsychotics treatment that a haplotype associated with lower dysbindin-1 expression correlated with better executive functions, providing further mechanistic support from mouse models.
- Diego Scheggia
- , Rosa Mastrogiacomo
- & Francesco Papaleo
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Article
| Open AccessA multi-modal MRI study of the central response to inflammation in rheumatoid arthritis
Many diseases, such as rheumatoid arthritis, are characterized by a chronic inflammatory state, but it is not clear whether or how this affects the brain. Here, the authors show that the severity of on-going inflammation predicts altered functional brain connectivity in people with rheumatoid arthritis.
- Andrew Schrepf
- , Chelsea M. Kaplan
- & Neil Basu
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Article
| Open AccessRapid and widespread white matter plasticity during an intensive reading intervention
White matter properties correlate with cognitive performance in a number of domains. Here the authors show that altering a child’s educational environment though a targeted intervention program induces rapid, large-scale changes in the white matter, and that these changes track the learning process.
- Elizabeth Huber
- , Patrick M. Donnelly
- & Jason D. Yeatman
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Article
| Open AccessConcurrence of form and function in developing networks and its role in synaptic pruning
How structure and function coevolve in developing brains is little understood. Here, the authors study a coupled model of network development and memory, and find that due to the feedback networks with some initial memory capacity evolve into heterogeneous structures with high memory performance.
- Ana P. Millán
- , J. J. Torres
- & J Marro
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Article
| Open AccessCREB controls cortical circuit plasticity and functional recovery after stroke
Increasing excitability in the peri-infarct area enhances motor recovery after stroke. Here the authors show that expressing CREB, a transcription factor known for its role in synaptic plasticity, or increasing activity of CREB-expressing cells near the stroke site improves recovery in an effect that is strong enough that it can be used to turn on and off motor recovery after stroke.
- L. Caracciolo
- , M. Marosi
- & S. T. Carmichael
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Article
| Open AccessDiverse populations of local interneurons integrate into the Drosophila adult olfactory circuit
Local interneurons (LNs) in the Drosophila olfactory system are highly diverse. Here, the authors labeled different LN types and described how different LN subtypes are integrated into the developing circuit.
- Nan-Fu Liou
- , Shih-Han Lin
- & Ya-Hui Chou
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Article
| Open AccessAn ensemble code in medial prefrontal cortex links prior events to outcomes during learning
Prefrontal cortex is involved in flexibly learning the correct behavioural strategies but the neural correlates of this process are not well understood. Here the authors show that reinforcement for a correct decision at behavioural transitions evokes ensemble firing patterns related to prior events.
- Silvia Maggi
- , Adrien Peyrache
- & Mark D. Humphries
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Article
| Open AccessEarly deprivation disruption of associative learning is a developmental pathway to depression and social problems
Early childhood deprivation such as institutionalization can greatly affect early development. Here, the authors study children who were raised in institutions but later randomly placed in foster care vs. not, to understand how early-life deprivation affects associative learning in adolescence.
- Margaret A. Sheridan
- , Katie A. McLaughlin
- & Charles A. Nelson
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Article
| Open AccessSpecific hippocampal representations are linked to generalized cortical representations in memory
Memory representations in cortex and hippocampus are reactivated during sharp-wave ripple (SWR) events. Here, the authors show that, in a familiar environment, this activity preferentially links spatially selective hippocampal cells and task general PFC representations, pointing to a potential neural mechanism for generalization of individual experiences.
- Jai Y. Yu
- , Daniel F. Liu
- & Loren M. Frank
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Article
| Open AccessPrecise temporal regulation of alternative splicing during neural development
The precise timing of neurodevelopmental splicing switches and the underlying regulatory mechanisms remain poorly understood. This study identifies two major waves of developmental switches under the control of distinct combinations of RNA-binding proteins in central and peripheral nervous systems.
- Sebastien M. Weyn-Vanhentenryck
- , Huijuan Feng
- & Chaolin Zhang
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Article
| Open AccessGut vagal sensory signaling regulates hippocampus function through multi-order pathways
Feeding-relevant vagal signaling occurs between the gastrointestinal tract and the brain, but it is unclear if this pathway influences cognitive processes. This study shows that endogenous gastrointestinal derived vagal sensory signaling promotes hippocampal-dependent memory function via a multi-order brainstem–septal pathway.
- Andrea N. Suarez
- , Ted M. Hsu
- & Scott E. Kanoski
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| Open AccessMapping higher-order relations between brain structure and function with embedded vector representations of connectomes
The function of a brain region is determined by the network it is embedded in. Here the authors implement the word2vec algorithm for connectomes generating a vector embedding of the connectivity structure for each node allowing inference about functional relationships between brain regions.
- Gideon Rosenthal
- , František Váša
- & Olaf Sporns
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Article
| Open AccessVariable number of TMC1-dependent mechanotransducer channels underlie tonotopic conductance gradients in the cochlea
Mechanoelectrical transduction channel (MET) current found in stereocilia of hair cells matures over the first postnatal week. Here the authors look at the contribution of transmembrane channel-like protein 1 and 2 (TMC1 and TMC2) to MET current during development of tonotopic gradients.
- Maryline Beurg
- , Runjia Cui
- & Bechara Kachar
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Article
| Open AccessCotransporter-mediated water transport underlying cerebrospinal fluid formation
Osmotic forces do not suffice to explain the rate of cerebrospinal fluid (CSF) production. Here, the authors show that the Na+/K+/2Cl− cotransporter in the choroid plexus contributes substantially to CSF production via its inherent ability to cotransport water.
- Annette B. Steffensen
- , Eva K. Oernbo
- & Nanna MacAulay
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Article
| Open AccessArtificial strain of human prions created in vitro
Synthetic prions have previously been generated from recombinant rodent PrP. Here the authors generate synthetic human prions, by seeding human PrP with CJD prions, and characterize its infectivity in mice.
- Chae Kim
- , Xiangzhu Xiao
- & Jiri G. Safar
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Article
| Open AccessReward probability and timing uncertainty alter the effect of dorsal raphe serotonin neurons on patience
Activation of serotonin neurons in the dorsal raphe nucleus promotes patience in waiting for future rewards. Here the authors show that this effect is maximal for high probability reward or high temporal reward uncertainty suggesting that it boosts the prior probability of reward.
- Katsuhiko Miyazaki
- , Kayoko W. Miyazaki
- & Kenji Doya
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Article
| Open AccessVariability in the location of high frequency oscillations during prolonged intracranial EEG recordings
High frequency oscillations (HFO) are a promising biomarker for identifying epileptogenic zones without the need to monitor spontaneous seizure episodes. Here the authors report that there is much variability in the location of HFOs offering a note of caution toward using HFO locations from short recordings as a guide for surgery.
- Stephen V. Gliske
- , Zachary T. Irwin
- & William C. Stacey
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| Open AccessRegulation of cortical activity and arousal by the matrix cells of the ventromedial thalamic nucleus
The ventromedial thalamus (VM) is thought to control cortical arousal through its diffuse projections to cortex. Here the authors record and manipulate the activity of calbindin1-positive matrix cells in VM and show that they bidirectionally regulate the sleep-wake transition.
- Sakiko Honjoh
- , Shuntaro Sasai
- & Chiara Cirelli
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Article
| Open AccessStudy of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.
- Gail Davies
- , Max Lam
- & Ian J. Deary
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Article
| Open AccessInharmonic speech reveals the role of harmonicity in the cocktail party problem
Harmonicity is associated with a single sound source and may be a useful cue with which to segregate the speech of multiple talkers. Here the authors introduce a method for perturbing the constituent frequencies of speech and show that violating harmonicity degrades intelligibility of speech mixtures.
- Sara Popham
- , Dana Boebinger
- & Josh H. McDermott
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Article
| Open AccessON-OFF receptive fields in auditory cortex diverge during development and contribute to directional sweep selectivity
Auditory cortex neurons exhibit distinct frequency tuning to sound onset and offset. Here the authors demonstrate that during development ON-OFF receptive fields diverge to occupy adjacent frequency ranges that may underlie their direction selective responses to frequency modulated sweeps.
- Joseph Sollini
- , Gaëlle A. Chapuis
- & Paul Chadderton
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| Open AccessHuman single neuron activity precedes emergence of conscious perception
The neuronal basis of spontaneous changes in conscious experience is unclear. Here, authors report nonselective medial frontal activity starting two seconds before a spontaneous change in visual perception, followed by selective medial temporal lobe activity, one second before the change.
- Hagar Gelbard-Sagiv
- , Liad Mudrik
- & Itzhak Fried
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Article
| Open AccessThe CaMKII/NMDA receptor complex controls hippocampal synaptic transmission by kinase-dependent and independent mechanisms
Calcium-calmodulin-dependent protein kinase II (CaMKII) is well known for its roles in synaptic plasticity. Using a series of molecular replacement experiments, the authors show that the kinase function of CaMKII is required for long-term plasticity and basal AMPA receptor-mediated transmission.
- Salvatore Incontro
- , Javier Díaz-Alonso
- & Roger A. Nicoll
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Article
| Open AccessRhodopsin-cyclases for photocontrol of cGMP/cAMP and 2.3 Å structure of the adenylyl cyclase domain
Cyclic AMP and cGMP orchestrate a variety of cellular responses. Here, authors characterize the cGMP producing rhodopsin-guanylyl cyclase from C. anguillulae and derived adenylyl cyclase by a biochemical and structural approach which demonstrates the usability of these cyclases for optogenetic applications.
- Ulrike Scheib
- , Matthias Broser
- & Peter Hegemann
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Article
| Open AccessTrait paranoia shapes inter-subject synchrony in brain activity during an ambiguous social narrative
Reactions to the same event can vary vastly based on multiple factors. Here the authors show that people with high trait-level paranoia process ambiguous information in a narrative differently and this can be attributed to greater activity in mentalizing brain regions during the moments of ambiguity.
- Emily S. Finn
- , Philip R. Corlett
- & R. Todd Constable
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Article
| Open AccessLarge-scale forward genetics screening identifies Trpa1 as a chemosensor for predator odor-evoked innate fear behaviors
TMT is a chemical that evokes innate defensive behaviors yet the molecular mechanisms are not well understood. Here the authors perform a large-scale forward genetics screen in mice and identify Trpa1, a pungency/irritancy receptor, as a chemosensor for predator odor-evoked innate fear and defensive behaviors.
- Yibing Wang
- , Liqin Cao
- & Qinghua Liu
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Article
| Open AccessDeep 2-photon imaging and artifact-free optogenetics through transparent graphene microelectrode arrays
Optical imaging and manipulation technologies cannot be easily integrated with electrical recordings due to generation of light-induced artifacts. Here the authors report the optimization of transparent graphene microelectrode fabrication to achieve artifact-free electrical recordings along with deep 2-photon imaging in vivo.
- Martin Thunemann
- , Yichen Lu
- & Duygu Kuzum
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Article
| Open AccessDlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons
In the hypothalamus, the arcuate nucleus (ARC) contains AgRP-neurons that regulate energy balance as well as GHRH-neurons that regulate linear growth. Here, the authors looked at how the transcription factors Dlx1/2 and Otp link development of AgRP- and GHRH-neurons.
- Bora Lee
- , Janghyun Kim
- & Jae W. Lee
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Article
| Open AccessA20 critically controls microglia activation and inhibits inflammasome-dependent neuroinflammation
As resident macrophages of the brain, microglia are important for neuroinflammatory responses. This work shows that nuclear factor kappa B regulatory protein A20 is important for microglia activation and regulation during inflammation of the central nervous system.
- Sofie Voet
- , Conor Mc Guire
- & Geert van Loo
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Article
| Open AccessAsynchronous suppression of visual cortex during absence seizures in stargazer mice
Absence epilepsy is associated with frequent generalized spike-wave seizures and loss of awareness. Here the authors use 2-photon calcium imaging of primary visual cortex in a genetic mouse model of absence epilepsy and find that cortical neurons are less active and more loosely coupled to the seizure EEG signature than previously believed.
- Jochen Meyer
- , Atul Maheshwari
- & Stelios Smirnakis
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Article
| Open AccessThirty loci identified for heart rate response to exercise and recovery implicate autonomic nervous system
Genome-wide association studies have identified multiple loci for resting heart rate (HR) but the genetic factors associated with HR increase during and HR recovery after exercise are less well studied. Here, the authors examine both traits in a two-stage GWAS design in up to 67,257 individuals from UK Biobank.
- Julia Ramírez
- , Stefan van Duijvenboden
- & Patricia B. Munroe
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Article
| Open AccessTissue and cellular rigidity and mechanosensitive signaling activation in Alexander disease
Alexander disease is a rare neurodegeneration caused by mutations in a glial gene GFAP. Here, Wang and colleagues show in animal models of Alexander disease that GFAP mutant brain and cells have greater tissue and cellular stiffness and greater activation of mechanosensitive signaling cascade.
- Liqun Wang
- , Jing Xia
- & Mel B. Feany
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Article
| Open AccessDiffusion markers of dendritic density and arborization in gray matter predict differences in intelligence
Previous studies suggest that individual differences in intelligence correlate with circuit complexity and dendritic arborization in the brain. Here the authors use NODDI, a diffusion MRI technique, to confirm that neurite density and arborization are inversely related to measures of intelligence.
- Erhan Genç
- , Christoph Fraenz
- & Rex E. Jung
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Article
| Open AccessNeural encoding and production of functional morphemes in the posterior temporal lobe
Functional morphemes allow us to express details about objects, events, and their relationships. Here, authors show that inhibiting a small cortical area within left posterior superior temporal lobe selectively impairs the ability to produce functional morphemes but does not impair other linguistic abilities.
- Daniel K. Lee
- , Evelina Fedorenko
- & Ziv M. Williams
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Article
| Open AccessTop-down descending facilitation of spinal sensory excitatory transmission from the anterior cingulate cortex
It is known that descending facilitation of spinal responses may contribute to chronic pain, however many studies have focussed on brainstem mechanisms. Here the authors show that stimulation of the anterior cingulate cortex increases excitatory transmission in the dorsal horn, and that this may be via a direct pathway independent of the brainstem.
- Tao Chen
- , Wataru Taniguchi
- & Min Zhuo
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Article
| Open AccessBelief state representation in the dopamine system
Dopamine neurons encode reward prediction errors (RPE) that report the mismatch between expected reward and outcome for a given state. Here the authors report that when there is uncertainty about the current state, RPEs are calculated on the probabilistic representation of the current state or belief state.
- Benedicte M. Babayan
- , Naoshige Uchida
- & Samuel. J. Gershman
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Article
| Open AccessOlfactory bulb acetylcholine release dishabituates odor responses and reinstates odor investigation
Habituation reduces neural responsiveness to prolonged irrelevant stimuli and dishabituation reverses these effects when a salient stimulus is encountered. Here the authors demonstrate that acetylcholine is involved in dishabituating odor responses in the mouse olfactory bulb.
- M. Cameron Ogg
- , Jordan M. Ross
- & Max L. Fletcher
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Article
| Open AccessCross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases
Reduced central corneal thickness (CCT) is observed in common eye diseases as well as in rare Mendelian disorders. Here, in a cross-ancestry GWAS, the authors identify 19 novel genetic loci associated with CCT, a subset of which is involved in rare corneal or connective tissue disorders.
- Adriana I. Iglesias
- , Aniket Mishra
- & Stuart MacGregor
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Article
| Open AccessTwo-photon imaging of neuronal activity in motor cortex of marmosets during upper-limb movement tasks
Marmosets are an important model organism in neuroscience but there has only been limited success in training them on behavioral tasks. Here the authors report their ability to train marmosets in various motor tasks and simultaneously image neural dynamics in motor cortex with 2-photon imaging.
- Teppei Ebina
- , Yoshito Masamizu
- & Masanori Matsuzaki
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Article
| Open AccessDistinct homeostatic modulations stabilize reduced postsynaptic receptivity in response to presynaptic DLK signaling
Dual leucine zipper kinase (DLK) activates an intrinsic neuronal response to injury and is also implicated in neurodegeneration. Here, Goel and Dickman characterize how postsynaptic targets adapt to presynaptic DLK signaling through a downregulation of synaptic strength.
- Pragya Goel
- & Dion Dickman
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Article
| Open AccessDirect neurotransmitter activation of voltage-gated potassium channels
M-current is conveyed by voltage-sensitive KCNQ channels, which are enriched in GABAergic neurons and are activated by anticonvulsants such as retigabine. Here the authors show that GABA directly activates KCNQ3, at the residue required for its anticonvulsant activity.
- Rían W. Manville
- , Maria Papanikolaou
- & Geoffrey W. Abbott
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Article
| Open AccessSema7A/PlxnCl signaling triggers activity-dependent olfactory synapse formation
The molecular mechanisms underlying synapse formation in the olfactory bulb are not fully understood. Here the authors demonstrate that semaphorin 7A on olfactory sensory neurons, and its receptor plexin C1 expressed on mitral and tufted cells, is required for correct synapse formation.
- Nobuko Inoue
- , Hirofumi Nishizumi
- & Hitoshi Sakano
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