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| Open AccessSingle-cell analysis reveals region-heterogeneous responses in rhesus monkey spinal cord with complete injury
The cellular responses below the lesion remain unclear after spinal cord injury (SCI). Here, authors show region-heterogeneous responses in the SCI monkey by single-cell transcriptomics analysis and uncover the mechanism of scaffold-based SCI repair.
- Yongheng Fan
- , Xianming Wu
- & Jianwu Dai
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Article
| Open AccessIntermediate filaments associate with aggresome-like structures in proteostressed C. elegans neurons and influence large vesicle extrusions as exophers
High neuronal proteostress can trigger the production of aggregate-filled exophers in C. elegans. Here authors show that such extrusion relies on aggregate-associated intermediate filaments and adaptors.
- Meghan Lee Arnold
- , Jason Cooper
- & Monica Driscoll
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Article
| Open AccessAn open resource combining multi-contrast MRI and microscopy in the macaque brain
Linking microscale cellular structures to macroscale features of the brain is required to fully understand its structure and function. Here, the authors present a resource which combines multi-contrast microscopy and MRI of a single whole macaque brain to facilitate multimodal analyses.
- Amy F. D. Howard
- , Istvan N. Huszar
- & Karla L. Miller
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Article
| Open AccessThreat gates visual aversion via theta activity in Tachykinergic neurons
A brief (maximum 250 characters, including spaces) summary; Please provide this summary in your cover letter. Animals often promote visual aversion in a threatening situation for survival. Tsuji et al. report in Drosophila that a single cluster of Tachykinergic neurons translate mechanical threats to gating of visual aversion through θ oscillation.
- Masato Tsuji
- , Yuto Nishizuka
- & Kazuo Emoto
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Article
| Open AccessGenes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types
Using transcriptomic data from human brain cells, the authors show that the expression patterns of the genes implicated in human cognition and brain evolution overlap in specific neuron types, and relate to cellular function and structure.
- Stan L. W. Driessens
- , Anna A. Galakhova
- & Natalia A. Goriounova
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Article
| Open AccessSynaptotagmin-1-dependent phasic axonal dopamine release is dispensable for basic motor behaviors in mice
Synaptotagmin 1 is involved in dopamine release. Here the authors investigate the effect of loss of Syt1 in midbrain dopaminergic neurons in mice, and find that unconditioned motor behaviour and motivation for food, are intact.
- Benoît Delignat-Lavaud
- , Jana Kano
- & Louis-Éric Trudeau
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Article
| Open AccessDrosophila motor neuron boutons remodel through membrane blebbing coupled with muscle contraction
Neuronal remodeling is critical for neuronal function. Here, the authors report that motor neurons use membrane blebbing coupled to muscle contraction as a mechanism for synaptic bouton formation, suggesting that mechanical force plays a key role in neuronal remodeling.
- Andreia R. Fernandes
- , João P. Martins
- & Rita O. Teodoro
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Article
| Open AccessAfferent convergence to a shared population of interneuron AMPA receptors
Glutamate that diffuses out of the synaptic cleft can have actions at distant receptors, a mode of transmission called spillover. Here, the authors find in the cerebellar cortex that glutamate spillover from climbing fibers activates synaptic AMPA receptors of molecular layer interneurons, allowing glutamate from an unconnected pathway to co-opt postsynaptic receptors.
- Reagan L. Pennock
- , Luke T. Coddington
- & Jacques I. Wadiche
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Article
| Open AccessMultisite regulation integrates multimodal context in sensory circuits to control persistent behavioral states in C. elegans
Animals must integrate multiple inputs to switch between behavioral states. Here, authors discover two C. elegans behavioral states and reveal a common regulatory logic through which they are controlled according to multimodal environmental changes.
- Saurabh Thapliyal
- , Isabel Beets
- & Dominique A. Glauser
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Article
| Open AccessGlycolytically impaired Drosophila glial cells fuel neural metabolism via β-oxidation
Drosophila are able to survive for several weeks in the absence of glial glycolysis. Here, the authors show that glial cells can utilize fatty acids to supply neurons under restrictive conditions and glial cells act as a metabolic sensor and induce mobilization of peripheral energy stores.
- Ellen McMullen
- , Helen Hertenstein
- & Stefanie Schirmeier
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Article
| Open AccessPhospholipase D3 degrades mitochondrial DNA to regulate nucleotide signaling and APP metabolism
Phospholipase D3 polymorphisms are linked to late-onset Alzheimer’s disease but the mechanisms are not understood. Van Acker and colleagues show that Phospholipase D3 processes mitochondrial DNA in lysosomes to maintain lysosomal homeostasis and proper degradation of the amyloid precursor protein.
- Zoë P. Van Acker
- , Anika Perdok
- & Wim Annaert
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Article
| Open AccessTransient photocurrents in a subthreshold evidence accumulator accelerate perceptual decisions
The rate at which third-order olfactory neurons integrate synaptic inputs to spike threshold is thought to determine the speed of odor discrimination in Drosophila. Here, authors compare the impact of subthreshold optogenetic membrane potential manipulations on decision-making.
- Timothy L. H. Wong
- , Clifford B. Talbot
- & Gero Miesenböck
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Article
| Open AccessParabolic avalanche scaling in the synchronization of cortical cell assemblies
The diversity of synchronized neuronal groups provides a challenge for brain theories. Here, the authors report that group size grows quadratically with duration in line with predictions for neuronal avalanches and brain dynamics being critical.
- Elliott Capek
- , Tiago L. Ribeiro
- & Dietmar Plenz
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Article
| Open AccessAssociations between in vitro, in vivo and in silico cell classes in mouse primary visual cortex
Understanding functional role of different neuronal cell types is challenging. Here the authors associate multi-modal in vitro cell properties with in vivo physiology of mouse visual cortex.
- Yina Wei
- , Anirban Nandi
- & Costas A. Anastassiou
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Article
| Open AccessGlucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism
GBA1 mutations cause Gaucher’s disease and are the strongest risk factor for Parkinson’s disease. Using stable cell lines and patient iPSCs, the authors show mitochondrial localization of GBA1, which may affect neurodegenerative disease risk.
- Pascale Baden
- , Maria Jose Perez
- & Michela Deleidi
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Article
| Open AccessHypothalamic melanin-concentrating hormone neurons integrate food-motivated appetitive and consummatory processes in rats
Food intake is determined by learned appetitive responses and physiological “appetition” signals after eating begins. Here, authors show melanin-concentrating hormone (MCH)-producing neurons integrate these processes to promote caloric intake.
- Keshav S. Subramanian
- , Logan Tierno Lauer
- & Scott E. Kanoski
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Article
| Open AccessSleep fMRI with simultaneous electrophysiology at 9.4 T in male mice
Mechanisms of sleep remain elusive. Here, authors developed mouse sleep fMRI based on simultaneous electrophysiology and mapped global and sequential state transition patterns, together with global patterns triggered by SWRs in NREM and awake states.
- Yalin Yu
- , Yue Qiu
- & Zhifeng Liang
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Article
| Open AccessPurkinje cell dopaminergic inputs to astrocytes regulate cerebellar-dependent behavior
The role of dopamine in the cerebellum remains relatively unexplored. Here, the authors report a dopamine system in the cerebellum in mice, where Purkinje cells supply dopamine and Bergmann glia express D1 receptors. Activation of D1 receptors is found to modulate Purkinje cell activity and to affect locomotor and social behaviors.
- Chang Li
- , Natalie B. Saliba
- & Wei Li
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Article
| Open AccessMultiplex translaminar imaging in the spinal cord of behaving mice
Fluorescence imaging of the spinal cord poses challenges, including depth of imaging. Here the authors describe a custom microscope and chronically implanted microprism that enables multicolor translaminar imaging of sensory and motor evoked activity in behaving mice, and show that spinal astrocytes show sensorimotor program-dependent calcium excitation.
- Pavel Shekhtmeyster
- , Erin M. Carey
- & Axel Nimmerjahn
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Article
| Open AccessAstrocytic lactate dehydrogenase A regulates neuronal excitability and depressive-like behaviors through lactate homeostasis in mice
The role of glycolysis in depression is unclear. Here the authors report a glycolytic deficit under social stress and demonstrate that astrocytic LDHA affects neuronal excitability and depressive-like behaviours via lactate homeostasis in mice.
- Shan Yao
- , Min-Dong Xu
- & Xiang-Dong Sun
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Article
| Open AccessAn updated suite of viral vectors for in vivo calcium imaging using intracerebral and retro-orbital injections in male mice
Genetically encoded Ca2+ indicators (GECIs) are used to measure neural activity. Here, authors screen GECI constructs for suitability with systemic injections and soma-targeting, and modify a soma-targeting peptide for improved expression rate.
- Sverre Grødem
- , Ingeborg Nymoen
- & Marianne Fyhn
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Article
| Open AccessGeneralized extinction of fear memory depends on co-allocation of synaptic plasticity in dendrites
How memories are modified by new experiences remain elusive. Here, authors show that specific or generalized modification of memories depends on whether synaptic changes associated with previous memories are segregated or co-exist in dendritic branches.
- Zhiwei Xu
- , Erez Geron
- & Wen-Biao Gan
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Article
| Open AccessSynaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates
ATG9 is the only transmembrane protein of the core autophagy machinery known to be present at presynapses. Here, the authors show that both synaptophysin and ATG9A vesicles assemble into condensates with synapsin but remain segregated from each other.
- Daehun Park
- , Yumei Wu
- & Pietro De Camilli
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Article
| Open AccessRabphilin-3A undergoes phase separation to regulate GluN2A mobility and surface clustering
GluN2A and GluN2B, two predominant Glu2N subunits of NMDARs in hippocampus and cortex, display distinct organization and mobility in the neuronal surface. Here, authors show Rph3A, a GluN2A-specific binding protein, undergoes liquid-liquid phase separation, which regulate mobility, synaptic and extrasynaptic surface clustering, synaptic localization and synaptic response of GluN2A.
- Lei Yang
- , Mengping Wei
- & Chen Zhang
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Article
| Open AccessSingle-cell transcriptomic analysis reveals diversity within mammalian spinal motor neurons
How molecular diversity in neurons links to versatile functions is elusive. Here the authors profiled embryonic spinal motor neurons with single-cell RNAseq and identified molecular subtypes targeting distinct muscle groups in different species.
- Ee Shan Liau
- , Suoqin Jin
- & Jun-An Chen
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Article
| Open AccessCalcium-permeable channelrhodopsins for the photocontrol of calcium signalling
To date, no Ca2 + -selective channelrhodopsins have been characterized. In this study, Fernandez Lahore et al. report two calcium-permeable channelrhodopsins (CapChR1 and 2) for the photocontrol of calcium signalling in excitable tissue.
- Rodrigo G. Fernandez Lahore
- , Niccolò P. Pampaloni
- & Peter Hegemann
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Article
| Open AccessDeep brain stimulation creates informational lesion through membrane depolarization in mouse hippocampus
The neurophysiological mechanisms of deep brain stimulation remain poorly understood. Through fluorescence voltage imaging of individual hippocampal neurons in awake mice, the authors show that deep brain stimulation causes membrane depolarization that impairs a neuron’s ability to respond to intrinsic network activity patterns and optogenetic somatic depolarization, thereby creating an informational lesion.
- Eric Lowet
- , Krishnakanth Kondabolu
- & Xue Han
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Article
| Open AccessA glutamate receptor C-tail recruits CaMKII to suppress retrograde homeostatic signaling
Presynaptic homeostatic plasticity adaptively enhances neurotransmitter release following diminished postsynaptic glutamate receptor functionality. Here the authors identify a calcium-independent signaling system where active CaMKII detects a short domain encoded in a glutamate receptor C-tail, which gates retrograde homeostatic communication at a model glutamatergic synapse.
- Sarah Perry
- , Yifu Han
- & Dion Dickman
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Article
| Open AccessParvalbumin basket cell myelination accumulates axonal mitochondria to internodes
How myelin controls energy usage in different neuronal cell types remains unclear. Here, using viral tools, live imaging and ultrastructural data, the authors show that in contrast to excitatory axons interneuron myelination boosts the clustering of mitochondria.
- Koen Kole
- , Bas J. B. Voesenek
- & Maarten H. P. Kole
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Article
| Open AccessDefinition of the estrogen negative feedback pathway controlling the GnRH pulse generator in female mice
Estrogen secreted by the ovary controls how the brain drives pulsatile reproductive hormone secretion. The authors show that in mice, estrogen receptor alpha within a specific population of hypothalamic kisspeptin neurons is the principal pathway through which estrogen brings about this classic negative feedback pathway common to all mammals.
- H. James McQuillan
- , Jenny Clarkson
- & Allan E. Herbison
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Article
| Open AccessChronic stress causes striatal disinhibition mediated by SOM-interneurons in male mice
Chronic stress can trigger or worsen motor symptoms in neuropsychiatric disorders. Here, the authors show that SOM interneurons in the striatum are involved in stress-induced motor behaviors.
- Diana Rodrigues
- , Luis Jacinto
- & Patricia Monteiro
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Article
| Open AccessA multivesicular body-like organelle mediates stimulus-regulated trafficking of olfactory ciliary transduction proteins
Odor stimuli are transduced in cilia of olfactory sensory neurons. Here the authors identify an odor stimulus-regulated organelle that specifically stores and releases transduction proteins in the dendrite.
- Devendra Kumar Maurya
- , Anna Berghard
- & Staffan Bohm
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Article
| Open AccessDiffusion MRI anisotropy in the cerebral cortex is determined by unmyelinated tissue features
In gray matter, the relative contributions of myelinated axons and other tissue features to diffusion MRI (dMRI) are poorly understood. Here the authors combine ex vivo high-resolution dMRI of marmoset brain with histological sections of the same brain, and their findings suggest that in cortex, dMRI does not match the spatial distribution of myelin in the gray matter.
- Colin Reveley
- , Frank Q. Ye
- & David A. Leopold
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Article
| Open AccessMicroglial debris is cleared by astrocytes via C4b-facilitated phagocytosis and degraded via RUBICON-dependent noncanonical autophagy in mice
Microglia are professional phagocytes in the CNS. However, which cells scavenge corpses of microglia is largely neglected. Peng and colleagues found that nonprofessional phagocytes (astrocyte) phagocytose the debris of professional phagocytes (microglia).
- Tian Zhou
- , Yuxin Li
- & Bo Peng
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Review Article
| Open AccessA consensus statement on detection of hippocampal sharp wave ripples and differentiation from other fast oscillations
While the contribution of sharp wave ripples in memory consolidation and decision-making is established in rodent models, our understanding of their role in human memory is incomplete. Here, the authors discuss common methodological challenges in detecting, analyzing, and reporting sharp wave ripples, then they suggest practical solutions to distinguish them from other high-frequency events
- Anli A. Liu
- , Simon Henin
- & György Buzsáki
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Article
| Open AccessCNS myelination requires VAMP2/3-mediated membrane expansion in oligodendrocytes
Understanding myelination is important for CNS plasticity and disease. Here the authors show exocytosis mediated by the vesicular SNARE proteins VAMP2/3 is involved in oligodendrocyte membrane expansion.
- Mable Lam
- , Koji Takeo
- & J. Bradley Zuchero
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Article
| Open AccessTranscriptomic architecture of nuclei in the marmoset CNS
Studies of cell heterogeneity in white matter in primates have been limited to date. Here the authors describe a marmoset brain cell atlas that bridges rodent and human data, revealing strong gray-white matter glial segregation.
- Jing-Ping Lin
- , Hannah M. Kelly
- & Daniel S. Reich
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Article
| Open AccessTranscriptional dynamics of murine motor neuron maturation in vivo and in vitro
Patel et al. show that gene expression and regulation in motor neurons is dynamic until juvenile age. A core subprogram (~40% of genes) is faithfully recapitulated in cultured motor neurons, with neuronal activity playing only a modulatory role.
- Tulsi Patel
- , Jennifer Hammelman
- & Hynek Wichterle
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Article
| Open AccessCa2+-modulated photoactivatable imaging reveals neuron-astrocyte glutamatergic circuitries within the nucleus accumbens
Neuron-astrocyte communication is fundamental for brain physiology, yet the heterogeneity in the functional interaction between these two elements remains poorly understood. Here we show how different neuron-astrocyte networks integrate information from distinct glutamatergic inputs.
- Irene Serra
- , Julio Esparza
- & Marta Navarrete
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Article
| Open AccessCell type-specific calcium imaging of central sensitization in mouse dorsal horn
Altered mechanosensation by application of capsaicin to the skin is thought to be spinally mediated. Here, the authors use Ca2+ imaging in spinal neurons and develop a cell profiling approach to identify populations involved in central sensitization.
- Charles Warwick
- , Joseph Salsovic
- & Sarah E. Ross
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Article
| Open AccessEarly postnatal serotonin modulation prevents adult-stage deficits in Arid1b-deficient mice through synaptic transcriptional reprogramming
ARID1B is a chromatin remodeler associated with autism spectrum disorders. Here the authors demonstrate that early postnatal serotonin modulation prevents adult stage deficits in Arid1b-deficient mice through synaptic transcriptional reprogramming.
- Hyosang Kim
- , Doyoun Kim
- & Eunjoon Kim
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Article
| Open AccessLysosomal exocytosis releases pathogenic α-synuclein species from neurons in synucleinopathy models
Release of α-synuclein aggregates by neurons instigates spread of pathology in synucleinopathies, but the mechanism remains unclear. Here the authors show that neuronally generated α-synuclein aggregates accumulate within neuronal lysosomes and are released via SNARE-dependent lysosomal exocytosis.
- Ying Xue Xie
- , Nima N. Naseri
- & Manu Sharma
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Article
| Open AccessA direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory
The mammalian hippocampal formation plays a key role in several higher brain functions. Here, the authors show that excitatory neurons in layer 6b of the mouse EC project to all sub-regions comprising the hippocampal formation and receive input from the CA1, thalamus and claustrum.
- Yoav Ben-Simon
- , Karola Kaefer
- & Peter Jonas
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Article
| Open AccessAβ42 oligomers trigger synaptic loss through CAMKK2-AMPK-dependent effectors coordinating mitochondrial fission and mitophagy
Loss of excitatory synapses occur prior to the formation of amyloid plaques in Alzheimer’s disease. Here the authors show in an animal model that the loss of synapses induced by amyloid-beta oligomers requires over-activation of a stress-response pathway inducing structural remodelling of mitochondria in dendrites of cortical and hippocampal neurons.
- Annie Lee
- , Chandana Kondapalli
- & Franck Polleux
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Article
| Open AccessTranscription factor network analysis identifies REST/NRSF as an intrinsic regulator of CNS regeneration in mice
Here the authors couple an integrative genomic analysis with substantial in vitro and in vivo experimental validation, identifying REST as a novel suppressor of a pro-regenerative gene program and CNS axon regeneration in mice.
- Yuyan Cheng
- , Yuqin Yin
- & Daniel H. Geschwind
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Article
| Open AccessDisruption of tubulin-alpha4a polyglutamylation prevents aggregation of hyper-phosphorylated tau and microglia activation in mice
Pathologic oligomerization of hyper-phosphorylated Tau is a hallmark of tauopathies. Here the authors show that the loss of tubulin a4 polyglutamylation reverses tau hyperphosphorylation, oligomerization and microglia activation in a tauopathy mouse.
- Torben Johann Hausrat
- , Philipp C. Janiesch
- & Matthias Kneussel
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Article
| Open AccessA synaptic signal for novelty processing in the hippocampus
Memory formation and recall are complementary processes within the hippocampus. Here the authors demonstrate a synaptic signal of novelty in the hippocampus and provide a computational framework for how such a novelty-driven switch may enable flexible encoding of new memories while preserving stable retrieval of familiar ones.
- Ruy Gómez-Ocádiz
- , Massimiliano Trippa
- & Christoph Schmidt-Hieber
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Article
| Open AccessSex-specific regulation of inhibition and network activity by local aromatase in the mouse hippocampus
Using a combination of molecular, genetic, functional and behavioural tools, this study describes the impact of brain synthesized estrogen in inhibitory neuronal function, network oscillations and hippocampal dependent memory.
- Alicia Hernández-Vivanco
- , Nuria Cano-Adamuz
- & Pablo Méndez
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Matters Arising
| Open AccessMotor deficits seen in microglial ablation mice could be due to non-specific damage from high dose diphtheria toxin treatment
- Jiyun Peng
- , Qian Zou
- & Bao-Ming Li