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  • Human Herpesvirus 6 Detection in Alzheimer’s Disease Cases and Controls across Multiple Cohorts
    Neuron (IF 14.403) Pub Date : 2020-01-23
    Mary Alice Allnutt; Kory Johnson; David A. Bennett; Sarah M. Connor; Juan C. Troncoso; Olga Pletnikova; Marilyn S. Albert; Susan M. Resnick; Sonja W. Scholz; Philip L. De Jager; Steven Jacobson

    The interplay between viral infection and Alzheimer’s disease (AD) has long been an area of interest, but proving causality has been elusive. Several recent studies have renewed the debate concerning the role of herpesviruses, and human herpesvirus 6 (HHV-6) in particular, in AD. We screened for HHV-6 detection across three independent AD brain repositories using (1) RNA sequencing (RNA-seq) datasets and (2) DNA samples extracted from AD and non-AD control brains. The RNA-seq data were screened for pathogens against taxon references from over 25,000 microbes, including 118 human viruses, whereas DNA samples were probed for PCR reactivity to HHV-6A and HHV-6B. HHV-6 demonstrated little specificity to AD brains over controls by either method, whereas other viruses, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), were detected at comparable levels. These direct methods of viral detection do not suggest an association between HHV-6 and AD.

    更新日期:2020-01-23
  • Time Warping Reveals Hidden Features of Neuronal Population Responses
    Neuron (IF 14.403) Pub Date : 2020-01-22
    Michael Okun

    Neuronal population responses can vary across trials as a result of differences in the relative timing of internal brain processes. In this issue of Neuron, Williams et al. (2020) present an algorithm for inferring and inverting such trial-to-trial differences, thereby revealing an a priori hidden, precise temporal structure of population responses.

    更新日期:2020-01-22
  • Aβ Puts the Alpha in Synuclein
    Neuron (IF 14.403) Pub Date : 2020-01-22
    Casey Cook; Leonard Petrucelli

    Neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease are characterized pathologically by aberrant protein accumulation, such as Aβ or α-synuclein deposition. In this issue of Neuron, Bassil et al. (2020) observed an exacerbation of α-syn pathology in the presence of Aβ plaques in vivo, with comorbid pathologies associated with greater neurodegeneration.

    更新日期:2020-01-22
  • Greasing the Wheels of Regeneration
    Neuron (IF 14.403) Pub Date : 2020-01-22
    Rafi Kohen; Roman J. Giger

    In this issue of Neuron, Yang et al. (2020) identify glycerolipid metabolism as a neuron-intrinsic mechanism that regulates axonal growth and regeneration. Shifting glycerolipid metabolism toward increased triglyceride synthesis blocks PNS neuron regeneration, whereas shifting it toward membrane phospholipid synthesis overcomes regeneration failure in CNS neurons.

    更新日期:2020-01-22
  • Deciphering Pyramidal Neuron Diversity: Delineating Perceptual Functions of Projection-Defined Neuronal Types
    Neuron (IF 14.403) Pub Date : 2020-01-22
    Ning-long Xu

    Axonal projection patterns are increasingly recognized as a defining feature for neuronal classification. How could such structural distinctions be linked to functions? In this issue of Neuron, Tang and Higley (2020) disambiguate behavior-level functions of two projection-defined subtypes of cortical projection neurons.

    更新日期:2020-01-22
  • International Brain Initiative: An Innovative Framework for Coordinated Global Brain Research Efforts
    Neuron (IF 14.403) Pub Date : 2020-01-22

    The International Brain Initiative (IBI) has been established to coordinate efforts across existing and emerging national and regional brain initiatives. This NeuroView describes how to be involved and the new opportunities for global collaboration that are emerging between scientists, scientific societies, funders, industry, government, and society.

    更新日期:2020-01-22
  • Thomas Blanpied
    Neuron (IF 14.403) Pub Date : 2020-01-22

    In an interview with Neuron, Dr. Thomas Blanpied talks about why he became a neuroscientist, what inspires him to investigate protein organization at synapses, politicization being one of the biggest challenges for science, and why passion is important for driving science forward.

    更新日期:2020-01-22
  • Communication, Cross Talk, and Signal Integration in the Adult Hippocampal Neurogenic Niche
    Neuron (IF 14.403) Pub Date : 2020-01-22
    Cinzia Vicidomini; Nannan Guo; Amar Sahay

    Radial glia-like neural stem cells (RGLs) in the dentate gyrus subregion of the hippocampus give rise to dentate granule cells (DGCs) and astrocytes throughout life, a process referred to as adult hippocampal neurogenesis. Adult hippocampal neurogenesis is sensitive to experiences, suggesting that it may represent an adaptive mechanism by which hippocampal circuitry is modified in response to environmental demands. Experiential information is conveyed to RGLs, progenitors, and adult-born DGCs via the neurogenic niche that is composed of diverse cell types, extracellular matrix, and afferents. Understanding how the niche performs its functions may guide strategies to maintain its health span and provide a permissive milieu for neurogenesis. Here, we first discuss representative contributions of niche cell types to regulation of neural stem cell (NSC) homeostasis and maturation of adult-born DGCs. We then consider mechanisms by which the activity of multiple niche cell types may be coordinated to communicate signals to NSCs. Finally, we speculate how NSCs integrate niche-derived signals to govern their regulation.

    更新日期:2020-01-22
  • Multiple Rhythm-Generating Circuits Act in Tandem with Pacemaker Properties to Control the Start and Speed of Locomotion
    Neuron (IF 14.403) Pub Date : 2020-01-22
    Jianren Song; Irene Pallucchi; Jessica Ausborn; Konstantinos Ampatzis; Maria Bertuzzi; Pierre Fontanel; Laurence D. Picton; Abdeljabbar El Manira
    更新日期:2020-01-22
  • A Role for the Locus Coeruleus in Hippocampal CA1 Place Cell Reorganization during Spatial Reward Learning
    Neuron (IF 14.403) Pub Date : 2020-01-21
    Alexandra Mansell Kaufman; Tristan Geiller; Attila Losonczy

    During spatial learning, hippocampal (HPC) place maps reorganize to represent new goal locations, but little is known about the circuit mechanisms facilitating these changes. Here, we examined how neuromodulation via locus coeruleus (LC) projections to HPC area CA1 (LC-CA1) regulates the overrepresentation of CA1 place cells near rewarded locations. Using two-photon calcium imaging, we monitored the activity of LC-CA1 fibers in the mouse dorsal HPC. We find that the LC-CA1 projection signals the translocation of a reward, predicting behavioral performance on a goal-oriented spatial learning task. An optogenetic stimulation mimicking this LC-CA1 activity induces place cell reorganization around a familiar reward, while its inhibition decreases the degree of overrepresentation around a translocated reward. Our results show that LC acts in conjunction with other factors to induce goal-directed reorganization of HPC representations and provide a better understanding of the role of neuromodulatory actions on HPC place map plasticity.

    更新日期:2020-01-22
  • LRRTM4: A Novel Regulator of Presynaptic Inhibition and Ribbon Synapse Arrangements of Retinal Bipolar Cells
    Neuron (IF 14.403) Pub Date : 2020-01-20
    Raunak Sinha; Tabrez J. Siddiqui; Nirmala Padmanabhan; Julie Wallin; Chi Zhang; Benyamin Karimi; Fred Rieke; Ann Marie Craig; Rachel O. Wong; Mrinalini Hoon

    LRRTM4 is a transsynaptic adhesion protein regulating glutamatergic synapse assembly on dendrites of central neurons. In the mouse retina, we find that LRRTM4 is enriched at GABAergic synapses on axon terminals of rod bipolar cells (RBCs). Knockout of LRRTM4 reduces RBC axonal GABAA and GABAC receptor clustering and disrupts presynaptic inhibition onto RBC terminals. LRRTM4 removal also perturbs the stereotyped output synapse arrangement at RBC terminals. Synaptic ribbons are normally apposed to two distinct postsynaptic “dyad” partners, but in the absence of LRRTM4, “monad” and “triad” arrangements are also formed. RBCs from retinas deficient in GABA release also demonstrate dyad mis-arrangements but maintain LRRTM4 expression, suggesting that defects in dyad organization in the LRRTM4 knockout could originate from reduced GABA receptor function. LRRTM4 is thus a key synapse organizing molecule at RBC terminals, where it regulates function of GABAergic synapses and assembly of RBC synaptic dyads.

    更新日期:2020-01-21
  • Estimation of Current and Future Physiological States in Insular Cortex
    Neuron (IF 14.403) Pub Date : 2020-01-16
    Yoav Livneh; Arthur U. Sugden; Joseph C. Madara; Rachel A. Essner; Vanessa I. Flores; Lauren A. Sugden; Jon M. Resch; Bradford B. Lowell; Mark L. Andermann
    更新日期:2020-01-17
  • Dopamine-Evoked Synaptic Regulation in the Nucleus Accumbens Requires Astrocyte Activity
    Neuron (IF 14.403) Pub Date : 2020-01-15
    Michelle Corkrum; Ana Covelo; Justin Lines; Luigi Bellocchio; Marc Pisansky; Kelvin Loke; Ruth Quintana; Patrick E. Rothwell; Rafael Lujan; Giovanni Marsicano; Eduardo D. Martin; Mark J. Thomas; Paulo Kofuji; Alfonso Araque

    Dopamine is involved in physiological processes like learning and memory, motor control and reward, and pathological conditions such as Parkinson’s disease and addiction. In contrast to the extensive studies on neurons, astrocyte involvement in dopaminergic signaling remains largely unknown. Using transgenic mice, optogenetics, and pharmacogenetics, we studied the role of astrocytes on the dopaminergic system. We show that in freely behaving mice, astrocytes in the nucleus accumbens (NAc), a key reward center in the brain, respond with Ca2+ elevations to synaptically released dopamine, a phenomenon enhanced by amphetamine. In brain slices, synaptically released dopamine increases astrocyte Ca2+, stimulates ATP/adenosine release, and depresses excitatory synaptic transmission through activation of presynaptic A1 receptors. Amphetamine depresses neurotransmission through stimulation of astrocytes and the consequent A1 receptor activation. Furthermore, astrocytes modulate the acute behavioral psychomotor effects of amphetamine. Therefore, astrocytes mediate the dopamine- and amphetamine-induced synaptic regulation, revealing a novel cellular pathway in the brain reward system.

    更新日期:2020-01-15
  • Amygdala Reward Neurons Form and Store Fear Extinction Memory
    Neuron (IF 14.403) Pub Date : 2020-01-14
    Xiangyu Zhang; Joshua Kim; Susumu Tonegawa

    The ability to extinguish conditioned fear memory is critical for adaptive control of fear response, and its impairment is a hallmark of emotional disorders like post-traumatic stress disorder (PTSD). Fear extinction is thought to take place when animals form a new memory that suppresses the original fear memory. However, little is known about the nature and the site of formation and storage of this new extinction memory. Here we demonstrate that a fear extinction memory engram is formed and stored in a genetically distinct basolateral amygdala (BLA) neuronal population that drives reward behaviors and antagonizes the BLA’s original fear neurons. Activation of fear extinction engram neurons and natural reward-responsive neurons overlap significantly in the BLA. Furthermore, these two neuronal subsets are mutually interchangeable in driving reward behaviors and fear extinction behaviors. Thus, fear extinction memory is a newly formed reward memory.

    更新日期:2020-01-15
  • Opposing Contributions of GABAergic and Glutamatergic Ventral Pallidal Neurons to Motivational Behaviors
    Neuron (IF 14.403) Pub Date : 2020-01-13
    Marcus Stephenson-Jones; Christian Bravo-Rivera; Sandra Ahrens; Alessandro Furlan; Xiong Xiao; Carolina Fernandes-Henriques; Bo Li

    The ventral pallidum (VP) is critical for invigorating reward seeking and is also involved in punishment avoidance, but how it contributes to such opposing behavioral actions remains unclear. Here, we show that GABAergic and glutamatergic VP neurons selectively control behavior in opposing motivational contexts. In vivo recording combined with optogenetics in mice revealed that these two populations oppositely encode positive and negative motivational value, are differentially modulated by animal’s internal state, and determine the behavioral response during motivational conflict. Furthermore, GABAergic VP neurons are essential for movements toward reward in a positive motivational context but suppress movements in an aversive context. In contrast, glutamatergic VP neurons are essential for movements to avoid a threat but suppress movements in an appetitive context. Our results indicate that GABAergic and glutamatergic VP neurons encode the drive for approach and avoidance, respectively, with the balance between their activities determining the type of motivational behavior.

    更新日期:2020-01-13
  • Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening
    Neuron (IF 14.403) Pub Date : 2020-01-13
    David J. Marcus; Gaurav Bedse; Andrew D. Gaulden; James D. Ryan; Veronika Kondev; Nathan D. Winters; Luis E. Rosas-Vidal; Megan Altemus; Ken Mackie; Francis S. Lee; Eric Delpire; Sachin Patel

    Functional coupling between the amygdala and the dorsomedial prefrontal cortex (dmPFC) has been implicated in the generation of negative affective states; however, the mechanisms by which stress increases amygdala-dmPFC synaptic strength and generates anxiety-like behaviors are not well understood. Here, we show that the mouse basolateral amygdala (BLA)-prelimbic prefrontal cortex (plPFC) circuit is engaged by stress and activation of this pathway in anxiogenic. Furthermore, we demonstrate that acute stress exposure leads to a lasting increase in synaptic strength within a reciprocal BLA-plPFC-BLA subcircuit. Importantly, we identify 2-arachidonoylglycerol (2-AG)-mediated endocannabinoid signaling as a key mechanism limiting glutamate release at BLA-plPFC synapses and the functional collapse of multimodal 2-AG signaling as a molecular mechanism leading to persistent circuit-specific synaptic strengthening and anxiety-like behaviors after stress exposure. These data suggest that circuit-specific impairment in 2-AG signaling could facilitate functional coupling between the BLA and plPFC and the translation of environmental stress to affective pathology.

    更新日期:2020-01-13
  • Functional Electron Microscopy (“Flash and Freeze”) of Identified Cortical Synapses in Acute Brain Slices
    Neuron (IF 14.403) Pub Date : 2020-01-09
    Carolina Borges-Merjane; Olena Kim; Peter Jonas
    更新日期:2020-01-09
  • Antidepressant Effects and Mechanisms of Group II mGlu Receptor-Specific Negative Allosteric Modulators
    Neuron (IF 14.403) Pub Date : 2020-01-08
    Liam E. Potter; Panos Zanos; Todd D. Gould

    In this issue of Neuron, Joffe et al. (2020) assess the antidepressant-relevant effects and underlying neural mechanisms of negative allosteric modulators selective for either metabotropic glutamate receptors 2 (mGlu2) or 3 (mGlu3). Negative modulation of both receptors enhanced excitatory glutamatergic input to mouse prefrontal cortex pyramidal cells, leading to antidepressant-relevant actions.

    更新日期:2020-01-08
  • The Spineless Origins of Prefrontal Cortex Dysfunction and Psychiatric Disorders
    Neuron (IF 14.403) Pub Date : 2020-01-08
    Simon J.B. Butt; Armin Lak

    Fundamental research into early circuits of the neocortex provides insight into the etiology of mental illness. In this issue of Neuron, Chini et al. (2020) probe the consequences of combined genetic and environmental perturbation on emergent network activity in the prefrontal cortex, identifying a window for possible intervention.

    更新日期:2020-01-08
  • Decoding Inter-individual Variability in Experience-Dependent Behavioral Plasticity
    Neuron (IF 14.403) Pub Date : 2020-01-08
    Navonil Banerjee; Elissa A. Hallem

    Inter-individual variability in behavioral flexibility is widespread throughout the animal kingdom, but its underlying mechanisms remain poorly understood. In this issue of Neuron, Beets et al. (2020) provide novel insights into the genetic basis of inter-individual differences in behavioral flexibility using the model nematode C. elegans.

    更新日期:2020-01-08
  • Glia: The Glue Holding Memories Together
    Neuron (IF 14.403) Pub Date : 2020-01-08
    Adi Doron; Inbal Goshen

    Adult oligodendrogenesis is regulated by neuronal activity and learning. Can it affect memory processes? In this issue of Neuron, Steadman et al. (2020) found that newly generated oligodendrocytes are crucial for memory acquisition and consolidation and required for the neuronal coupling between brain regions known to be involved in memory.

    更新日期:2020-01-08
  • Of Man and Mice: Translational Research in Neurotechnology
    Neuron (IF 14.403) Pub Date : 2020-01-08
    Thomas Stieglitz

    Emerging technological developments in nano- and microsystems engineering have delivered powerful tools for neuroscience research over the last 50 years. However, only a few neural implants have been transferred into clinical practice. Challenges and opportunities for translational research are discussed herein.

    更新日期:2020-01-08
  • Turning Touch into Perception
    Neuron (IF 14.403) Pub Date : 2020-01-08
    Ranulfo Romo; Román Rossi-Pool

    Many brain areas modulate their activity during vibrotactile tasks. The activity from these areas may code the stimulus parameters, stimulus perception, or perceptual reports. Here, we discuss findings obtained in behaving monkeys aimed to understand these processes. In brief, neurons from the somatosensory thalamus and primary somatosensory cortex (S1) only code the stimulus parameters during the stimulation periods. In contrast, areas downstream of S1 code the stimulus parameters during not only the task components but also perception. Surprisingly, the midbrain dopamine system is an actor not considered before in perception. We discuss the evidence that it codes the subjective magnitude of a sensory percept. The findings reviewed here may help us to understand where and how sensation transforms into perception in the brain.

    更新日期:2020-01-08
  • Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression
    Neuron (IF 14.403) Pub Date : 2020-01-08
    Bing Bai; Xusheng Wang; Yuxin Li; Ping-Chung Chen; Kaiwen Yu; Kaushik Kumar Dey; Jay M. Yarbro; Xian Han; Brianna M. Lutz; Shuquan Rao; Yun Jiao; Jeffrey M. Sifford; Jonghee Han; Minghui Wang; Haiyan Tan; Timothy I. Shaw; Ji-Hoon Cho; Suiping Zhou; Junmin Peng
    更新日期:2020-01-08
  • Astrocyte Unfolded Protein Response Induces a Specific Reactivity State that Causes Non-Cell-Autonomous Neuronal Degeneration
    Neuron (IF 14.403) Pub Date : 2020-01-07
    Heather L. Smith; Oliver J. Freeman; Adrian J. Butcher; Staffan Holmqvist; Ibrahim Humoud; Tobias Schätzl; Daniel T. Hughes; Nicholas C. Verity; Dean P. Swinden; Joseph Hayes; Lis de Weerd; David H. Rowitch; Robin J.M. Franklin; Giovanna R. Mallucci
    更新日期:2020-01-07
  • TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge
    Neuron (IF 14.403) Pub Date : 2020-01-02
    Alicia A. Nugent; Karin Lin; Bettina van Lengerich; Steve Lianoglou; Laralynne Przybyla; Sonnet S. Davis; Ceyda Llapashtica; Junhua Wang; Do Jin Kim; Dan Xia; Anthony Lucas; Sulochanadevi Baskaran; Patrick C.G. Haddick; Melina Lenser; Timothy K. Earr; Ju Shi; Jason C. Dugas; Benjamin J. Andreone; Gilbert Di Paolo
    更新日期:2020-01-02
  • m6A mRNA Methylation Is Essential for Oligodendrocyte Maturation and CNS Myelination
    Neuron (IF 14.403) Pub Date : 2019-12-31
    Huan Xu; Yulia Dzhashiashvili; Ankeeta Shah; Rejani B. Kunjamma; Yi-lan Weng; Benayahu Elbaz; Qili Fei; Joshua S. Jones; Yang I. Li; Xiaoxi Zhuang; Guo-li Ming; Chuan He; Brian Popko

    The molecular mechanisms that govern the maturation of oligodendrocyte lineage cells remain unclear. Emerging studies have shown that N6-methyladenosine (m6A), the most common internal RNA modification of mammalian mRNA, plays a critical role in various developmental processes. Here, we demonstrate that oligodendrocyte lineage progression is accompanied by dynamic changes in m6A modification on numerous transcripts. In vivo conditional inactivation of an essential m6A writer component, METTL14, results in decreased oligodendrocyte numbers and CNS hypomyelination, although oligodendrocyte precursor cell (OPC) numbers are normal. In vitro Mettl14 ablation disrupts postmitotic oligodendrocyte maturation and has distinct effects on OPC and oligodendrocyte transcriptomes. Moreover, the loss of Mettl14 in oligodendrocyte lineage cells causes aberrant splicing of myriad RNA transcripts, including those that encode the essential paranodal component neurofascin 155 (NF155). Together, our findings indicate that dynamic RNA methylation plays an important regulatory role in oligodendrocyte development and CNS myelination.

    更新日期:2019-12-31
  • Cortical Synaptic AMPA Receptor Plasticity during Motor Learning
    Neuron (IF 14.403) Pub Date : 2019-12-31
    Richard H. Roth; Robert H. Cudmore; Han L. Tan; Ingie Hong; Yong Zhang; Richard L. Huganir

    Modulation of synaptic strength through trafficking of AMPA receptors (AMPARs) is a fundamental mechanism underlying synaptic plasticity, learning, and memory. However, the dynamics of AMPAR trafficking in vivo and its correlation with learning have not been resolved. Here, we used in vivo two-photon microscopy to visualize surface AMPARs in mouse cortex during the acquisition of a forelimb reaching task. Daily training leads to an increase in AMPAR levels at a subset of spatially clustered dendritic spines in the motor cortex. Surprisingly, we also observed increases in spine AMPAR levels in the visual cortex. There, synaptic potentiation depends on the availability of visual input during motor training, and optogenetic inhibition of visual cortex activity impairs task performance. These results indicate that motor learning induces widespread cortical synaptic potentiation by increasing the net trafficking of AMPARs into spines, including in non-motor brain regions.

    更新日期:2019-12-31
  • Glucocerebrosidase Activity Modulates Neuronal Susceptibility to Pathological α-Synuclein Insult
    Neuron (IF 14.403) Pub Date : 2019-12-30
    Michael X. Henderson; Samantha Sedor; Ian McGeary; Eli J. Cornblath; Chao Peng; Dawn M. Riddle; Howard L. Li; Bin Zhang; Hannah J. Brown; Modupe F. Olufemi; Danielle S. Bassett; John Q. Trojanowski; Virginia M.Y. Lee
    更新日期:2019-12-30
  • Huntington’s Disease Pathogenesis Is Modified In Vivo by Alfy/Wdfy3 and Selective Macroautophagy
    Neuron (IF 14.403) Pub Date : 2019-12-30
    Leora M. Fox; Kiryung Kim; Christopher W. Johnson; Shawei Chen; Katherine R. Croce; Matheus B. Victor; Evelien Eenjes; Joan R. Bosco; Lisa K. Randolph; Ioannis Dragatsis; Joanna M. Dragich; Andrew S. Yoo; Ai Yamamoto

    Despite being an autosomal dominant disorder caused by a known coding mutation in the gene HTT, Huntington’s disease (HD) patients with similar trinucleotide repeat mutations can have an age of onset that varies by decades. One likely contributing factor is the genetic heterogeneity of patients that might modify their vulnerability to disease. We report that although the heterozygous depletion of the autophagy adaptor protein Alfy/Wdfy3 has no consequence in control mice, it significantly accelerates age of onset and progression of HD pathogenesis. Alfy is required in the adult brain for the autophagy-dependent clearance of proteinaceous deposits, and its depletion in mice and neurons derived from patient fibroblasts accelerates the aberrant accumulation of this pathological hallmark shared across adult-onset neurodegenerative diseases. These findings indicate that selectively compromising the ability to eliminate aggregated proteins is a pathogenic driver, and the selective elimination of aggregates may confer disease resistance.

    更新日期:2019-12-30
  • In Vivo Imaging of the Coupling between Neuronal and CREB Activity in the Mouse Brain
    Neuron (IF 14.403) Pub Date : 2019-12-26
    Tal Laviv; Benjamin Scholl; Paula Parra-Bueno; Beth Foote; Chuqiu Zhang; Long Yan; Yuki Hayano; Jun Chu; Ryohei Yasuda

    Sensory experiences cause long-term modifications of neuronal circuits by modulating activity-dependent transcription programs that are vital for regulation of long-term synaptic plasticity and memory. However, it has not been possible to precisely determine the interaction between neuronal activity patterns and transcription factor activity. Here we present a technique using two-photon fluorescence lifetime imaging (2pFLIM) with new FRET biosensors to chronically image in vivo signaling of CREB, an activity-dependent transcription factor important for synaptic plasticity, at single-cell resolution. Simultaneous imaging of the red-shifted CREB sensor and GCaMP permitted exploration of how experience shapes the interplay between CREB and neuronal activity in the neocortex of awake mice. Dark rearing increased the sensitivity of CREB activity to Ca2+ elevations and prolonged the duration of CREB activation to more than 24 h in the visual cortex. This technique will allow researchers to unravel the transcriptional dynamics underlying experience-dependent plasticity in the brain.

    更新日期:2019-12-27
  • Human-Specific ARHGAP11B Acts in Mitochondria to Expand Neocortical Progenitors by Glutaminolysis
    Neuron (IF 14.403) Pub Date : 2019-12-26
    Takashi Namba; Judit Dóczi; Anneline Pinson; Lei Xing; Nereo Kalebic; Michaela Wilsch-Bräuninger; Katherine R. Long; Samir Vaid; Janelle Lauer; Aliona Bogdanova; Barbara Borgonovo; Anna Shevchenko; Patrick Keller; David Drechsel; Teymuras Kurzchalia; Pauline Wimberger; Christos Chinopoulos; Wieland B. Huttner

    The human-specific gene ARHGAP11B is preferentially expressed in neural progenitors of fetal human neocortex and increases abundance and proliferation of basal progenitors (BPs), which have a key role in neocortex expansion. ARHGAP11B has therefore been implicated in the evolutionary expansion of the human neocortex, but its mode of action has been unknown. Here, we show that ARHGAP11B is imported into mitochondria, where it interacts with the adenine nucleotide translocase (ANT) and inhibits the mitochondrial permeability transition pore (mPTP). BP expansion by ARHGAP11B requires its presence in mitochondria, and pharmacological inhibition of ANT function or mPTP opening mimic BP expansion by ARHGAP11B. Searching for the underlying metabolic basis, we find that BP expansion by ARHGAP11B requires glutaminolysis, the conversion of glutamine to glutamate for the tricarboxylic acid (TCA) cycle. Hence, an ARHGAP11B-induced, mitochondria-based effect on BP metabolism that is a hallmark of highly mitotically active cells appears to underlie its role in neocortex expansion.

    更新日期:2019-12-27
  • Synergy of Distinct Dopamine Projection Populations in Behavioral Reinforcement
    Neuron (IF 14.403) Pub Date : 2019-12-23
    Gabriel Heymann; Yong S. Jo; Kathryn L. Reichard; Naomi McFarland; Charles Chavkin; Richard D. Palmiter; Marta E. Soden; Larry S. Zweifel

    Dopamine neurons of the ventral tegmental area (VTA) regulate reward association and motivation. It remains unclear whether there are distinct dopamine populations to mediate these functions. Using mouse genetics, we isolated two populations of dopamine-producing VTA neurons with divergent projections to the nucleus accumbens (NAc) core and shell. Inhibition of VTA-core-projecting neurons disrupted Pavlovian reward learning, and activation of these cells promoted the acquisition of an instrumental response. VTA-shell-projecting neurons did not regulate Pavlovian reward learning and could not facilitate acquisition of an instrumental response, but their activation could drive robust responding in a previously learned instrumental task. Both populations are activated simultaneously by cues, actions, and rewards, and this co-activation is required for robust reinforcement of behavior. Thus, there are functionally distinct dopamine populations in the VTA for promoting motivation and reward association, which operate on the same timescale to optimize behavioral reinforcement.

    更新日期:2019-12-23
  • Structural Insights into Electrophile Irritant Sensing by the Human TRPA1 Channel
    Neuron (IF 14.403) Pub Date : 2019-12-19
    Yang Suo; Zilong Wang; Lejla Zubcevic; Allen L. Hsu; Qianru He; Mario J. Borgnia; Ru-Rong Ji; Seok-Yong Lee

    Transient receptor potential channel subfamily A member 1 (TRPA1) is a Ca2+-permeable cation channel that serves as one of the primary sensors of environmental irritants and noxious substances. Many TRPA1 agonists are electrophiles that are recognized by TRPA1 via covalent bond modifications of specific cysteine residues located in the cytoplasmic domains. However, a mechanistic understanding of electrophile sensing by TRPA1 has been limited due to a lack of high-resolution structural information. Here, we present the cryoelectron microscopy (cryo-EM) structures of nanodisc-reconstituted ligand-free TRPA1 and TRPA1 in complex with the covalent agonists JT010 and BITC at 2.8, 2.9, and 3.1 Å, respectively. Our structural and functional studies provide the molecular basis for electrophile recognition by the extraordinarily reactive C621 in TRPA1 and mechanistic insights into electrophile-dependent conformational changes in TRPA1. This work also provides a platform for future drug development targeting TRPA1.

    更新日期:2019-12-19
  • Glutamate Receptors: Not Just for Excitation
    Neuron (IF 14.403) Pub Date : 2019-12-18
    Katherine L. Villa; Elly Nedivi

    In this issue of Neuron, Fossati et al. (2019) report a new constellation of players regulating inhibitory synaptogenesis. They show that GluD1, through a non-canonical ionotropic-independent mechanism, controls GABAergic synapse formation via trans-synaptic interactions mediated by extracellular cerebellin-4. They identify ARHGEF12 and PPP1R12A as GluD1 intracellular interactors and downstream effectors.

    更新日期:2019-12-19
  • Insulin-like Peptides as Agents of Social Change
    Neuron (IF 14.403) Pub Date : 2019-12-18
    Benjamin Brissette; Niels Ringstad

    Many behaviors promote reproduction or food finding. These critical functions of behavior can conflict; successful reproductive strategies can grow populations to the point where food is depleted. In this issue of Neuron, Wu et al. (2019) show how the nematode C. elegans detects crowding to change feeding behavior by coupling pheromone sensing to signaling via insulin-like peptides.

    更新日期:2019-12-19
  • The Dialog of Primary and Non-primary Auditory Cortex at the ‘Cocktail Party’
    Neuron (IF 14.403) Pub Date : 2019-12-18
    Elia Formisano; Lars Hausfeld

    In this issue of Neuron, O’Sullivan et al. (2019) measured electro-cortical responses to “cocktail party” speech mixtures in neurosurgical patients and demonstrated that the selective enhancement of attended speech is achieved through the adaptive weighting of primary auditory cortex output by non-primary auditory cortex.

    更新日期:2019-12-19
  • Therapeutic Targeting of mTORC2 in mTORopathies
    Neuron (IF 14.403) Pub Date : 2019-12-18
    Brianne Dentel; Christine Ochoa Escamilla; Peter T. Tsai

    Dysregulated mTOR contributes to neurodevelopmental dysfunction. A new study (Chen et al., 2019) demonstrates that suppression of mTORC2, not mTORC1, ameliorates survival, seizures, and abnormal behaviors in a Pten mutant model, highlighting mTORC2 as a potential therapeutic target in mTORopathies.

    更新日期:2019-12-19
  • Dorsal and Ventral Hippocampal Sharp-Wave Ripples Activate Distinct Nucleus Accumbens Networks
    Neuron (IF 14.403) Pub Date : 2019-12-18
    Marielena Sosa; Hannah R. Joo; Loren M. Frank

    Memories of positive experiences link places, events, and reward outcomes. These memories recruit interactions between the hippocampus and nucleus accumbens (NAc). Both dorsal and ventral hippocampus (dH and vH) project to the NAc, but it remains unknown whether dH and vH act in concert or separately to engage NAc representations related to space and reward. We recorded simultaneously from the dH, vH, and NAc of rats during an appetitive spatial task and focused on hippocampal sharp-wave ripples (SWRs) to identify times of memory reactivation across brain regions. Here, we show that dH and vH awake SWRs occur asynchronously and activate distinct and opposing patterns of NAc spiking. Only NAc neurons activated during dH SWRs were tuned to task- and reward-related information. These temporally and anatomically separable hippocampal-NAc interactions point to distinct channels of mnemonic processing in the NAc, with the dH-NAc channel specialized for spatial task and reward information.

    更新日期:2019-12-19
  • Molecular Tuning of the Axonal Mitochondrial Ca2+ Uniporter Ensures Metabolic Flexibility of Neurotransmission
    Neuron (IF 14.403) Pub Date : 2019-12-17
    Ghazaleh Ashrafi; Jaime de Juan-Sanz; Ryan J. Farrell; Timothy A. Ryan
    更新日期:2019-12-18
  • Dopaminergic and Prefrontal Basis of Learning from Sensory Confidence and Reward Value
    Neuron (IF 14.403) Pub Date : 2019-12-16
    Armin Lak; Michael Okun; Morgane M. Moss; Harsha Gurnani; Karolina Farrell; Miles J. Wells; Charu Bai Reddy; Adam Kepecs; Kenneth D. Harris; Matteo Carandini

    Deciding between stimuli requires combining their learned value with one’s sensory confidence. We trained mice in a visual task that probes this combination. Mouse choices reflected not only present confidence and past rewards but also past confidence. Their behavior conformed to a model that combines signal detection with reinforcement learning. In the model, the predicted value of the chosen option is the product of sensory confidence and learned value. We found precise correlates of this variable in the pre-outcome activity of midbrain dopamine neurons and of medial prefrontal cortical neurons. However, only the latter played a causal role: inactivating medial prefrontal cortex before outcome strengthened learning from the outcome. Dopamine neurons played a causal role only after outcome, when they encoded reward prediction errors graded by confidence, influencing subsequent choices. These results reveal neural signals that combine reward value with sensory confidence and guide subsequent learning.

    更新日期:2019-12-17
  • Nicotinamide Pathway-Dependent Sirt1 Activation Restores Calcium Homeostasis to Achieve Neuroprotection in Spinocerebellar Ataxia Type 7
    Neuron (IF 14.403) Pub Date : 2019-12-16
    Colleen A. Stoyas; David D. Bushart; Pawel M. Switonski; Jacqueline M. Ward; Akshay Alaghatta; Mi-bo Tang; Chenchen Niu; Mandheer Wadhwa; Haoran Huang; Alex Savchenko; Karim Gariani; Fang Xie; Joseph R. Delaney; Terry Gaasterland; Johan Auwerx; Vikram G. Shakkottai; Albert R. La Spada
    更新日期:2019-12-17
  • A Discrete Presynaptic Vesicle Cycle for Neuromodulator Receptors
    Neuron (IF 14.403) Pub Date : 2019-12-11
    Damien Jullié, Miriam Stoeber, Jean-Baptiste Sibarita, Hanna L. Zieger, Thomas M. Bartol, Seksiri Arttamangkul, Terrence J. Sejnowski, Eric Hosy, Mark von Zastrow
    更新日期:2019-12-11
  • The Transition from Evaluation to Selection Involves Neural Subspace Reorganization in Core Reward Regions
    Neuron (IF 14.403) Pub Date : 2019-12-10
    Seng Bum Michael Yoo, Benjamin Y. Hayden

    Economic choice proceeds from evaluation, in which we contemplate options, to selection, in which we weigh options and choose one. These stages must be differentiated so that decision makers do not proceed to selection before evaluation is complete. We examined responses of neurons in two core reward regions, orbitofrontal (OFC) and ventromedial prefrontal cortex (vmPFC), during two-option choice with asynchronous offer presentation. Our data suggest that neurons selective during the first (presumed evaluation) and second (presumed comparison and selection) offer epochs come from a single pool. Stage transition is accompanied by a shift toward orthogonality in the low-dimensional population response manifold. Nonetheless, the relative position of each option in driving responses in the population subspace is preserved. The orthogonalization we observe supports the hypothesis that the transition from evaluation to selection leads to reorganization of response subspace and suggests a mechanism by which value-related signals are prevented from prematurely driving choice.

    更新日期:2019-12-11
  • Integrative and Network-Specific Connectivity of the Basal Ganglia and Thalamus Defined in Individuals
    Neuron (IF 14.403) Pub Date : 2019-12-10
    Deanna J. Greene, Scott Marek, Evan M. Gordon, Joshua S. Siegel, Caterina Gratton, Timothy O. Laumann, Adrian W. Gilmore, Jeffrey J. Berg, Annie L. Nguyen, Donna Dierker, Andrew N. Van, Mario Ortega, Dillan J. Newbold, Jacqueline M. Hampton, Ashley N. Nielsen, Kathleen B. McDermott, Jarod L. Roland, Scott A. Norris, Nico U.F. Dosenbach
    更新日期:2019-12-11
  • Daily Oscillation of the Excitation-Inhibition Balance in Visual Cortical Circuits
    Neuron (IF 14.403) Pub Date : 2019-12-09
    Michelle C.D. Bridi, Fang-Jiao Zong, Xia Min, Nancy Luo, Trinh Tran, Jiaqian Qiu, Daniel Severin, Xue-Ting Zhang, Guanglin Wang, Zheng-Jiang Zhu, Kai-Wen He, Alfredo Kirkwood

    A balance between synaptic excitation and inhibition (E/I balance) maintained within a narrow window is widely regarded to be crucial for cortical processing. In line with this idea, the E/I balance is reportedly comparable across neighboring neurons, behavioral states, and developmental stages and altered in many neurological disorders. Motivated by these ideas, we examined whether synaptic inhibition changes over the 24-h day to compensate for the well-documented sleep-dependent changes in synaptic excitation. We found that, in pyramidal cells of visual and prefrontal cortices and hippocampal CA1, synaptic inhibition also changes over the 24-h light/dark cycle but, surprisingly, in the opposite direction of synaptic excitation. Inhibition is upregulated in the visual cortex during the light phase in a sleep-dependent manner. In the visual cortex, these changes in the E/I balance occurred in feedback, but not feedforward, circuits. These observations open new and interesting questions on the function and regulation of the E/I balance.

    更新日期:2019-12-11
  • Antibody Therapy Targeting RAN Proteins Rescues C9 ALS/FTD Phenotypes in C9orf72 Mouse Model
    Neuron (IF 14.403) Pub Date : 2019-12-09
    Lien Nguyen, Fabio Montrasio, Amrutha Pattamatta, Solaleh Khoramian Tusi, Olgert Bardhi, Kevin D. Meyer, Lindsey Hayes, Katsuya Nakamura, Monica Banez-Coronel, Alyssa Coyne, Shu Guo, Lauren A. Laboissonniere, Yuanzheng Gu, Saravanakumar Narayanan, Benjamin Smith, Roger M. Nitsch, Mark W. Kankel, Mia Rushe, Laura P.W. Ranum

    The intronic C9orf72 G4C2 expansion, the most common genetic cause of ALS and FTD, produces sense- and antisense-expansion RNAs and six dipeptide repeat-associated, non-ATG (RAN) proteins, but their roles in disease are unclear. We generated high-affinity human antibodies targeting GA or GP RAN proteins. These antibodies cross the blood-brain barrier and co-localize with intracellular RAN aggregates in C9-ALS/FTD BAC mice. In cells, α-GA1 interacts with TRIM21, and α-GA1 treatment reduced GA levels, increased GA turnover, and decreased RAN toxicity and co-aggregation of proteasome and autophagy proteins to GA aggregates. In C9-BAC mice, α-GA1 reduced GA as well as GP and GR proteins, improved behavioral deficits, decreased neuroinflammation and neurodegeneration, and increased survival. Glycosylation of the Fc region of α-GA1 is important for cell entry and efficacy. These data demonstrate that RAN proteins drive C9-ALS/FTD in C9-BAC transgenic mice and establish a novel therapeutic approach for C9orf72 ALS/FTD and other RAN-protein diseases.

    更新日期:2019-12-11
  • Continuous and Discrete Neuron Types of the Adult Murine Striatum
    Neuron (IF 14.403) Pub Date : 2019-12-05
    Geoffrey Stanley, Ozgun Gokce, Robert C. Malenka, Thomas C. Südhof, Stephen R. Quake

    The mammalian striatum is involved in many complex behaviors and yet is composed largely of a single neuron class: the spiny projection neuron (SPN). It is unclear to what extent the functional specialization of the striatum is due to the molecular specialization of SPN subtypes. We sought to define the molecular and anatomical diversity of adult SPNs using single-cell RNA sequencing (scRNA-seq) and quantitative RNA in situ hybridization (ISH). We computationally distinguished discrete versus continuous heterogeneity in scRNA-seq data and found that SPNs in the striatum can be classified into four major discrete types with no implied spatial relationship between them. Within these discrete types, we find continuous heterogeneity encoding spatial gradients of gene expression and defining anatomical location in a combinatorial mechanism. Our results suggest that neuronal circuitry has a substructure at far higher resolution than is typically interrogated, which is defined by the precise identity and location of a neuron.

    更新日期:2019-12-06
  • Usp9X Controls Ankyrin-Repeat Domain Protein Homeostasis during Dendritic Spine Development
    Neuron (IF 14.403) Pub Date : 2019-12-05
    Sehyoun Yoon, Euan Parnell, Maria Kasherman, Marc P. Forrest, Kristoffer Myczek, Susitha Premarathne, Michelle C. Sanchez Vega, Michael Piper, Thomas H.J. Burne, Lachlan A. Jolly, Stephen A. Wood, Peter Penzes
    更新日期:2019-12-05
  • A Basal Forebrain-Cingulate Circuit in Macaques Decides It Is Time to Act
    Neuron (IF 14.403) Pub Date : 2019-12-05
    Nima Khalighinejad, Alessandro Bongioanni, Lennart Verhagen, Davide Folloni, David Attali, Jean-Francois Aubry, Jerome Sallet, Matthew F.S. Rushworth

    The medial frontal cortex has been linked to voluntary action, but an explanation of why decisions to act emerge at particular points in time has been lacking. We show that, in macaques, decisions about whether and when to act are predicted by a set of features defining the animal’s current and past context; for example, respectively, cues indicating the current average rate of reward and recent previous voluntary action decisions. We show that activity in two brain areas—the anterior cingulate cortex and basal forebrain—tracks these contextual factors and mediates their effects on behavior in distinct ways. We use focused transcranial ultrasound to selectively and effectively stimulate deep in the brain, even as deep as the basal forebrain, and demonstrate that alteration of activity in the two areas changes decisions about when to act.

    更新日期:2019-12-05
  • Relax, Don’t RAN Translate It
    Neuron (IF 14.403) Pub Date : 2019-12-04
    Katherine M. Wilson, Bhavana Muralidharan, Adrian M. Isaacs

    The (GGGGCC)n repeat expansion in C9orf72, which is the most common cause of frontotemporal dementia and amyotrophic lateral sclerosis, is translated through repeat-associated non-AUG (RAN) translation. In this issue of Neuron, Cheng et al. (2019) report that the helicase DDX3X, which unwinds (or relaxes) RNA, suppresses RAN translation and toxicity.

    更新日期:2019-12-04
  • Signal Amplification in Drosophila Olfactory Receptor Neurons
    Neuron (IF 14.403) Pub Date : 2019-12-04
    Byoung Soo Kim, Greg S.B. Suh

    Olfactory receptor neurons (ORNs) transform scant chemical inputs into significant neural signals. This transformation requires signal amplification. In this issue of Neuron, Ng et al. (2019) identified a mechanism by which the signals evoked by pheromones are amplified in the ORNs that selectively promote courtship behavior in Drosophila.

    更新日期:2019-12-04
  • TREK for High-Speed and High-Frequency Conduction through the Axon
    Neuron (IF 14.403) Pub Date : 2019-12-04
    Pablo Ávalos Prado, Guillaume Sandoz

    In this issue of Neuron, Kanda et al. (2019) find that the two-pore domain potassium channels TRAAK and TREK1 drive axonal action potential repolarization for high-speed and high-frequency nervous impulses in mammalian myelinated nerves.

    更新日期:2019-12-04
  • Quiescence of Adult Mammalian Neural Stem Cells: A Highly Regulated Rest
    Neuron (IF 14.403) Pub Date : 2019-12-04
    Noelia Urbán, Isabelle Maria Blomfield, François Guillemot

    Neural stem cells in the adult mammalian brain are the source of new neurons that contribute to complex sensory and cognitive functions. Most adult neural stem cells are maintained in a state of reversible cell cycle arrest, also called quiescence. Quiescent neural stem cells present a low rate of metabolic activity and a high sensitivity to their local signaling environment, and they can be activated by diverse physiological stimuli. The balance between stem cell quiescence and activity determines not only the rate of neurogenesis but also the long-term maintenance of the stem cell pool and the neurogenic capacity of the aging brain. In recent years, significant progress has been made in characterizing quiescent stem cells thanks to the introduction of new genomic and imaging techniques. We discuss in this review our current understanding of neural stem cell quiescence and its regulation by intrinsic and systemic factors.

    更新日期:2019-12-04
  • Binary Fate Choice between Closely Related Interneuronal Types Is Determined by a Fezf1-Dependent Postmitotic Transcriptional Switch
    Neuron (IF 14.403) Pub Date : 2019-12-04
    Yi-Rong Peng, Rebecca E. James, Wenjun Yan, Jeremy N. Kay, Alex L. Kolodkin, Joshua R. Sanes
    更新日期:2019-12-04
  • Alpha Synchrony and the Neurofeedback Control of Spatial Attention
    Neuron (IF 14.403) Pub Date : 2019-12-04
    Yasaman Bagherzadeh, Daniel Baldauf, Dimitrios Pantazis, Robert Desimone

    Decreases in alpha synchronization are correlated with enhanced attention, whereas alpha increases are correlated with inattention. However, correlation is not causality, and synchronization may be a byproduct of attention rather than a cause. To test for a causal role of alpha synchrony in attention, we used MEG neurofeedback to train subjects to manipulate the ratio of alpha power over the left versus right parietal cortex. We found that a comparable alpha asymmetry developed over the visual cortex. The alpha training led to corresponding asymmetrical changes in visually evoked responses to probes presented in the two hemifields during training. Thus, reduced alpha was associated with enhanced sensory processing. Testing after training showed a persistent bias in attention in the expected directions. The results support the proposal that alpha synchrony plays a causal role in modulating attention and visual processing, and alpha training could be used for testing hypotheses about synchrony.

    更新日期:2019-12-04
  • A Differential Circuit via Retino-Colliculo-Pulvinar Pathway Enhances Feature Selectivity in Visual Cortex through Surround Suppression
    Neuron (IF 14.403) Pub Date : 2019-12-04
    Qi Fang, Xiao-lin Chou, Bo Peng, Wen Zhong, Li I. Zhang, Huizhong Whit Tao
    更新日期:2019-12-04
  • Neurons that Function within an Integrator to Promote a Persistent Behavioral State in Drosophila
    Neuron (IF 14.403) Pub Date : 2019-12-03
    Yonil Jung, Ann Kennedy, Hui Chiu, Farhan Mohammad, Adam Claridge-Chang, David J. Anderson
    更新日期:2019-12-04
  • Epigenetic Signaling in Glia Controls Presynaptic Homeostatic Plasticity
    Neuron (IF 14.403) Pub Date : 2019-12-03
    Tingting Wang, Danielle T. Morency, Nathan Harris, Graeme W. Davis

    Epigenetic gene regulation shapes neuronal fate in the embryonic nervous system. Post-embryonically, epigenetic signaling within neurons has been associated with impaired learning, autism, ataxia, and schizophrenia. Epigenetic factors are also enriched in glial cells. However, little is known about epigenetic signaling in glia and nothing is known about the intersection of glial epigenetic signaling and presynaptic homeostatic plasticity. During a screen for genes involved in presynaptic homeostatic synaptic plasticity, we identified an essential role for the histone acetyltransferase and deubiquitinase SAGA complex in peripheral glia. We present evidence that the SAGA complex is necessary for homeostatic plasticity, demonstrating involvement of four new genes in homeostatic plasticity. This is also evidence that glia participate in presynaptic homeostatic plasticity, invoking previously unexplored intercellular, homeostatic signaling at a tripartite synapse. We show, mechanistically, SAGA signaling regulates the composition of and signaling from the extracellular matrix during homeostatic plasticity.

    更新日期:2019-12-04
  • Vasomotion as a Driving Force for Paravascular Clearance in the Awake Mouse Brain
    Neuron (IF 14.403) Pub Date : 2019-12-03
    Susanne J. van Veluw, Steven S. Hou, Maria Calvo-Rodriguez, Michal Arbel-Ornath, Austin C. Snyder, Matthew P. Frosch, Steven M. Greenberg, Brian J. Bacskai

    Paravascular drainage of solutes, including β-amyloid (Aβ), appears to be an important process in brain health and diseases such as Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA). However, the major driving force for clearance remains largely unknown. Here we used in vivo two-photon microscopy in awake head-fixed mice to assess the role of spontaneous vasomotion in paravascular clearance. Vasomotion correlated with paravascular clearance of fluorescent dextran from the interstitial fluid. Increasing the amplitude of vasomotion by means of visually evoked vascular responses resulted in increased clearance rates in the visual cortex of awake mice. Evoked vascular reactivity was impaired in mice with CAA, which corresponded to slower clearance rates. Our findings suggest that low-frequency arteriolar oscillations drive drainage of solutes. Targeting naturally occurring vasomotion in patients with CAA or AD may be a promising early therapeutic option for prevention of Aβ accumulation in the brain.

    更新日期:2019-12-04
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