Transneuronal propagation of mutant huntingtin contributes to non-cell autonomous pathology in neurons.

Abstract:

:In Huntington's disease (HD), whether transneuronal spreading of mutant huntingtin (mHTT) occurs and its contribution to non-cell autonomous damage in brain networks is largely unknown. We found mHTT spreading in three different neural network models: human neurons integrated in the neural network of organotypic brain slices of HD mouse model, an ex vivo corticostriatal slice model and the corticostriatal pathway in vivo. Transneuronal propagation of mHTT was blocked by two different botulinum neurotoxins, each known for specifically inactivating a single critical component of the synaptic vesicle fusion machinery. Moreover, healthy human neurons in HD mouse model brain slices displayed non-cell autonomous changes in morphological integrity that were more pronounced when these neurons bore mHTT aggregates. Altogether, our findings suggest that transneuronal propagation of mHTT might be an important and underestimated contributor to the pathophysiology of HD.

journal_name

Nat Neurosci

journal_title

Nature neuroscience

authors

Pecho-Vrieseling E,Rieker C,Fuchs S,Bleckmann D,Esposito MS,Botta P,Goldstein C,Bernhard M,Galimberti I,Müller M,Lüthi A,Arber S,Bouwmeester T,van der Putten H,Di Giorgio FP

doi

10.1038/nn.3761

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

1064-72

issue

8

eissn

1097-6256

issn

1546-1726

pii

nn.3761

journal_volume

17

pub_type

杂志文章
  • BMPs inhibit neurogenesis by a mechanism involving degradation of a transcription factor.

    abstract::Bone morphogenetic proteins (BMPs), negative regulators of neural determination in the early embryo, were found to be potent inhibitors of neurogenesis in olfactory epithelium (OE) cultures. BMPs 2, 4 or 7 decreased the number of proliferating progenitor cells and blocked production of olfactory receptor neurons (ORNs...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/7251

    authors: Shou J,Rim PC,Calof AL

    更新日期:1999-04-01 00:00:00

  • The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals.

    abstract::Transformation of mechanical energy into ionic currents is essential for touch, hearing and nociception. Although DEG/ENaC proteins are believed to form sensory mechanotransduction channels, the evidence for this role remains indirect. By recording from C. elegans touch receptor neurons in vivo, we found that external...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1362

    authors: O'Hagan R,Chalfie M,Goodman MB

    更新日期:2005-01-01 00:00:00

  • Synaptic N6-methyladenosine (m6A) epitranscriptome reveals functional partitioning of localized transcripts.

    abstract::A localized transcriptome at the synapse facilitates synapse-, stimulus- and transcript-specific local protein synthesis in response to neuronal activity. While enzyme-mediated mRNA modifications are known to regulate cellular mRNA turnover, the role of these modifications in regulating synaptic RNA has not been studi...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/s41593-018-0173-6

    authors: Merkurjev D,Hong WT,Iida K,Oomoto I,Goldie BJ,Yamaguti H,Ohara T,Kawaguchi SY,Hirano T,Martin KC,Pellegrini M,Wang DO

    更新日期:2018-07-01 00:00:00

  • Octopamine fuels fighting flies.

    abstract::The neural basis of aggression is poorly understood. A study in this issue used genetic scalpels to dissect the circuitry of the fly brain and identified a small cluster of octopaminergic neurons that can make a fly fighting mad. ...

    journal_title:Nature neuroscience

    pub_type: 评论,杂志文章,评审

    doi:10.1038/nn0908-989

    authors: Potter CJ,Luo L

    更新日期:2008-09-01 00:00:00

  • Distinct roles for direct and indirect pathway striatal neurons in reinforcement.

    abstract::Dopamine signaling is implicated in reinforcement learning, but the neural substrates targeted by dopamine are poorly understood. We bypassed dopamine signaling itself and tested how optogenetic activation of dopamine D1 or D2 receptor–expressing striatal projection neurons influenced reinforcement learning in mice. S...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3100

    authors: Kravitz AV,Tye LD,Kreitzer AC

    更新日期:2012-06-01 00:00:00

  • Paternal recognition of adult offspring mediated by newly generated CNS neurons.

    abstract::In mammals, olfaction is often used to distinguish individuals on the basis of their unique odor types (genetically programmed body odors). Parental-offspring recognition behavior is mediated, in part, by learning and processing of different odor types and is crucial for reproductive success. Maternal recognition beha...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.2550

    authors: Mak GK,Weiss S

    更新日期:2010-06-01 00:00:00

  • Action anticipation and motor resonance in elite basketball players.

    abstract::We combined psychophysical and transcranial magnetic stimulation studies to investigate the dynamics of action anticipation and its underlying neural correlates in professional basketball players. Athletes predicted the success of free shots at a basket earlier and more accurately than did individuals with comparable ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.2182

    authors: Aglioti SM,Cesari P,Romani M,Urgesi C

    更新日期:2008-09-01 00:00:00

  • 5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response.

    abstract::Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants, but the mechanisms by which they influence behavior are only partially resolved. Adult hippocampal neurogenesis is necessary for some of the responses to SSRIs, but it is not known whether mature dentate gyrus granule cells (DG GCs) also ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.4116

    authors: Samuels BA,Anacker C,Hu A,Levinstein MR,Pickenhagen A,Tsetsenis T,Madroñal N,Donaldson ZR,Drew LJ,Dranovsky A,Gross CT,Tanaka KF,Hen R

    更新日期:2015-11-01 00:00:00

  • Modeling behaviorally relevant neural dynamics enabled by preferential subspace identification.

    abstract::Neural activity exhibits complex dynamics related to various brain functions, internal states and behaviors. Understanding how neural dynamics explain specific measured behaviors requires dissociating behaviorally relevant and irrelevant dynamics, which is not achieved with current neural dynamic models as they are le...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/s41593-020-00733-0

    authors: Sani OG,Abbaspourazad H,Wong YT,Pesaran B,Shanechi MM

    更新日期:2021-01-01 00:00:00

  • Endoplasmic reticulum stress in disorders of myelinating cells.

    abstract::Myelinating cells, oligodendrocytes in the CNS and Schwann cells in the peripheral nervous system produce an enormous amount of plasma membrane during the myelination process, making them particularly susceptible to disruptions of the secretory pathway. Endoplasmic reticulum stress, initiated by the accumulation of un...

    journal_title:Nature neuroscience

    pub_type: 杂志文章,评审

    doi:10.1038/nn.2273

    authors: Lin W,Popko B

    更新日期:2009-04-01 00:00:00

  • Neuronal activity drives matching of pre- and postsynaptic function during synapse maturation.

    abstract::The structure and function of presynaptic and postsynaptic compartments varies markedly in neurons, but little is known about how they are functionally arranged with respect to each other. In rat hippocampal neurons, we found that, although they are structurally correlated from the early moments of formation, synapses...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.2826

    authors: Kay L,Humphreys L,Eickholt BJ,Burrone J

    更新日期:2011-06-01 00:00:00

  • Activity recall in a visual cortical ensemble.

    abstract::Cue-triggered recall of learned temporal sequences is an important cognitive function that has been attributed to higher brain areas. Here recordings in both anesthetized and awake rats demonstrate that after repeated stimulation with a moving spot that evoked sequential firing of an ensemble of primary visual cortex ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3036

    authors: Xu S,Jiang W,Poo MM,Dan Y

    更新日期:2012-01-22 00:00:00

  • From neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior.

    abstract::Over the past two centuries, prevalent models of energy and glucose homeostasis have emerged from careful anatomical descriptions in tandem with an understanding of cellular physiology. More recent technological advances have culminated in the identification of peripheral and central factors that influence neural circ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章,评审

    doi:10.1038/nn.3217

    authors: Williams KW,Elmquist JK

    更新日期:2012-10-01 00:00:00

  • A Drosophila kinesin required for synaptic bouton formation and synaptic vesicle transport.

    abstract::The morphological transition of growth cones to synaptic boutons characterizes synaptogenesis. Here we have isolated mutations in immaculate connections (imac; CG8566), a previously uncharacterized Drosophila gene encoding a member of the Kinesin-3 family. Whereas earlier studies in Drosophila implicated Kinesin-1 in ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1936

    authors: Pack-Chung E,Kurshan PT,Dickman DK,Schwarz TL

    更新日期:2007-08-01 00:00:00

  • Separate circuitries encode the hedonic and nutritional values of sugar.

    abstract::Sugar exerts its potent reinforcing effects via both gustatory and post-ingestive pathways. It is, however, unknown whether sweetness and nutritional signals engage segregated brain networks to motivate ingestion. We found in mice that separate basal ganglia circuitries mediated the hedonic and nutritional actions of ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.4224

    authors: Tellez LA,Han W,Zhang X,Ferreira TL,Perez IO,Shammah-Lagnado SJ,van den Pol AN,de Araujo IE

    更新日期:2016-03-01 00:00:00

  • Activity-dependent decrease of excitability in rat hippocampal neurons through increases in I(h).

    abstract::Hippocampal long-term potentiation (LTP) induced by theta-burst pairing of Schaffer collateral inputs and postsynaptic firing is associated with localized increases in synaptic strength and dendritic excitability. Using the same protocol, we now demonstrate a decrease in cellular excitability that was blocked by the h...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1568

    authors: Fan Y,Fricker D,Brager DH,Chen X,Lu HC,Chitwood RA,Johnston D

    更新日期:2005-11-01 00:00:00

  • Machine translation of cortical activity to text with an encoder-decoder framework.

    abstract::A decade after speech was first decoded from human brain signals, accuracy and speed remain far below that of natural speech. Here we show how to decode the electrocorticogram with high accuracy and at natural-speech rates. Taking a cue from recent advances in machine translation, we train a recurrent neural network t...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/s41593-020-0608-8

    authors: Makin JG,Moses DA,Chang EF

    更新日期:2020-04-01 00:00:00

  • Mesopontine median raphe regulates hippocampal ripple oscillation and memory consolidation.

    abstract::Sharp wave-associated field oscillations (∼200 Hz) of the hippocampus, referred to as ripples, are believed to be important for consolidation of explicit memory. Little is known about how ripples are regulated by other brain regions. We found that the median raphe region (MnR) is important for regulating hippocampal r...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3998

    authors: Wang DV,Yau HJ,Broker CJ,Tsou JH,Bonci A,Ikemoto S

    更新日期:2015-05-01 00:00:00

  • Stages of processing in face perception: an MEG study.

    abstract::Here we used magnetoencephalography (MEG) to investigate stages of processing in face perception in humans. We found a face-selective MEG response occurring only 100 ms after stimulus onset (the 'M100'), 70 ms earlier than previously reported. Further, the amplitude of this M100 response was correlated with successful...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn909

    authors: Liu J,Harris A,Kanwisher N

    更新日期:2002-09-01 00:00:00

  • A single in-vivo exposure to delta 9THC blocks endocannabinoid-mediated synaptic plasticity.

    abstract::Endogenous cannabinoids (eCB) mediate synaptic plasticity in brain regions involved in learning and reward. Here we show that in mice, a single in-vivo exposure to Delta 9-tetrahydrocannabinol (THC) abolishes the retrograde signaling that underlies eCB-mediated synaptic plasticity in both nucleus accumbens (NAc) and h...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1251

    authors: Mato S,Chevaleyre V,Robbe D,Pazos A,Castillo PE,Manzoni OJ

    更新日期:2004-06-01 00:00:00

  • A myelin-related transcriptomic profile is shared by Pitt-Hopkins syndrome models and human autism spectrum disorder.

    abstract::Autism spectrum disorder (ASD) is genetically heterogeneous with convergent symptomatology, suggesting common dysregulated pathways. In this study, we analyzed brain transcriptional changes in five mouse models of Pitt-Hopkins syndrome (PTHS), a syndromic form of ASD caused by mutations in the TCF4 gene, but not the T...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/s41593-019-0578-x

    authors: Phan BN,Bohlen JF,Davis BA,Ye Z,Chen HY,Mayfield B,Sripathy SR,Cerceo Page S,Campbell MN,Smith HL,Gallop D,Kim H,Thaxton CL,Simon JM,Burke EE,Shin JH,Kennedy AJ,Sweatt JD,Philpot BD,Jaffe AE,Maher BJ

    更新日期:2020-03-01 00:00:00

  • Morphology of Heschl's gyrus reflects enhanced activation in the auditory cortex of musicians.

    abstract::Using magnetoencephalography (MEG), we compared the processing of sinusoidal tones in the auditory cortex of 12 non-musicians, 12 professional musicians and 13 amateur musicians. We found neurophysiological and anatomical differences between groups. In professional musicians as compared to non-musicians, the activity ...

    journal_title:Nature neuroscience

    pub_type: 临床试验,杂志文章

    doi:10.1038/nn871

    authors: Schneider P,Scherg M,Dosch HG,Specht HJ,Gutschalk A,Rupp A

    更新日期:2002-07-01 00:00:00

  • Tonotopic reorganization of developing auditory brainstem circuits.

    abstract::A fundamental organizing principle of auditory brain circuits is tonotopy, the orderly representation of the sound frequency to which neurons are most sensitive. Tonotopy arises from the coding of frequency along the cochlea and the topographic organization of auditory pathways. The mechanisms that underlie the establ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章,评审

    doi:10.1038/nn.2332

    authors: Kandler K,Clause A,Noh J

    更新日期:2009-06-01 00:00:00

  • XTRPC1-dependent chemotropic guidance of neuronal growth cones.

    abstract::Calcium arising through release from intracellular stores and from influx across the plasma membrane is essential for signalling by specific guidance cues and by factors that inhibit axon regeneration. The mediators of calcium influx in these cases are largely unknown. Transient receptor potential channels (TRPCs) bel...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1459

    authors: Shim S,Goh EL,Ge S,Sailor K,Yuan JP,Roderick HL,Bootman MD,Worley PF,Song H,Ming GL

    更新日期:2005-06-01 00:00:00

  • Convergent cortical innervation of striatal projection neurons.

    abstract::Anatomical studies have led to the assertion that intratelencephalic and pyramidal tract cortical neurons innervate different striatal projection neurons. To test this hypothesis, we measured the responses of mouse striatal neurons to optogenetic activation of intratelencephalic and pyramidal tract axons. Contrary to ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3397

    authors: Kress GJ,Yamawaki N,Wokosin DL,Wickersham IR,Shepherd GM,Surmeier DJ

    更新日期:2013-06-01 00:00:00

  • The hippocampus is necessary for enhancements and impairments of learning following stress.

    abstract::The hippocampus is often considered to be an important site for stress and learning interactions; however, it has never been demonstrated whether these effects require the hippocampus. In the current study, hippocampal lesions prevented both enhancements of learning after stress in male rats and impairments of learnin...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1973

    authors: Bangasser DA,Shors TJ

    更新日期:2007-11-01 00:00:00

  • Correlating whisker behavior with membrane potential in barrel cortex of awake mice.

    abstract::To investigate synaptic events underlying sensory perception, we made whole-cell membrane potential recordings of barrel cortex neurons in awake mice while recording whisker-related behavior. During quiet periods, we recorded slow, large-amplitude membrane potential changes, which switched during whisking to small, fa...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1690

    authors: Crochet S,Petersen CC

    更新日期:2006-05-01 00:00:00

  • Reinforcement learning in populations of spiking neurons.

    abstract::Population coding is widely regarded as an important mechanism for achieving reliable behavioral responses despite neuronal variability. However, standard reinforcement learning slows down with increasing population size, as the global reward signal becomes less and less related to the performance of any single neuron...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.2264

    authors: Urbanczik R,Senn W

    更新日期:2009-03-01 00:00:00

  • Stress resilience is promoted by a Zfp189-driven transcriptional network in prefrontal cortex.

    abstract::Understanding the transcriptional changes that are engaged in stress resilience may reveal novel antidepressant targets. Here we use gene co-expression analysis of RNA-sequencing data from brains of resilient mice to identify a gene network that is unique to resilience. Zfp189, which encodes a previously unstudied zin...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/s41593-019-0462-8

    authors: Lorsch ZS,Hamilton PJ,Ramakrishnan A,Parise EM,Salery M,Wright WJ,Lepack AE,Mews P,Issler O,McKenzie A,Zhou X,Parise LF,Pirpinias ST,Ortiz Torres I,Kronman HG,Montgomery SE,Loh YE,Labonté B,Conkey A,Symonds AE,Nev

    更新日期:2019-09-01 00:00:00

  • State-related and item-related neural correlates of successful memory encoding.

    abstract::Neuroimaging studies show that the efficacy of long-term memory encoding of a stimulus is indexed by transient neural activity elicited by that stimulus. Here, we show that successful memory encoding is also indexed by neural activity that is tonically maintained throughout a study task. Using functional magnetic reso...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn967

    authors: Otten LJ,Henson RN,Rugg MD

    更新日期:2002-12-01 00:00:00