| 1. |
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| 2. |
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| 3. |
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| 4. |
- Aizman, O, et al.
(författare)
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Anatomical and physiological evidence for D-1 and D-2 dopamine receptor colocalization in neostriatal neurons
- 2000
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 3:3, s. 226-230
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Tidskriftsartikel (refereegranskat)abstract
- Despite the importance of dopamine signaling, it remains unknown if the two major subclasses of dopamine receptors exist on the same or distinct populations of neurons. Here we used confocal microscopy to demonstrate that virtually all striatal neurons, both in vitro and in vivo, contained dopamine receptors of both classes. We also provide functional evidence for such colocalization: in essentially all neurons examined, fenoldopam, an agonist of the D-1 subclass of receptors, inhibited both the Na+/K+ pump and tetrodotoxin (TTX)-sensitive sodium channels, and quinpirole, an agonist of the Dr subclass of receptors, activated TTX-sensitive sodium channels. Thus D-1 and D-2 classes of ligands may functionally interact in virtually all dopamine-responsive neurons within the basal ganglia.
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| 5. |
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| 6. |
- Akbarian, S, et al.
(författare)
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The PsychENCODE project
- 2015
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Ingår i: Nature neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 18:12, s. 1707-1712
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Arenas, E
(författare)
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Parkinson's disease in the single-cell era
- 2022
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Ingår i: Nature neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 25:5, s. 536-538
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Barr, Gordon A, et al.
(författare)
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Transitions in infant learning are modulated by dopamine in the amygdala
- 2009
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 12, s. 1367-1369
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Tidskriftsartikel (refereegranskat)abstract
- Behavioral transitions characterize development. Young infant rats paradoxically prefer odors that are paired with shock, but older pups learn aversions. This transition is amygdala and corticosterone dependent. Using microarrays and microdialysis, we found downregulated dopaminergic presynaptic function in the amygdala with preference learning. Corticosterone-injected 8-d-old pups and untreated 12-d-old pups learned aversions and had dopaminergic upregulation in the amygdala. Dopamine injection into the amygdala changed preferences to aversions, whereas dopamine antagonism reinstated preference learning.
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| 9. |
- Bartoletti, Alessandro, et al.
(författare)
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Environmental enrichment prevents effects of dark-rearing in the rat visual cortex
- 2004
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 7:3, s. 215-216
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Tidskriftsartikel (refereegranskat)abstract
- Environmental enrichment potentiates neural plasticity, enhancing acquisition and consolidation of memory traces. In the sensory cortices, after cortical circuit maturation and sensory function acquisition are completed, neural plasticity declines and the critical period 'closes'. In the visual cortex, this process can be prevented by dark-rearing, and here we show that environmental enrichment can promote physiological maturation and consolidation of visual cortical connections in dark-reared rats, leading to critical period closure.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Blomqvist, Anders, et al.
(författare)
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OBITUARY: A. D. (Bud) Craig, Jr. (1951-2023)
- 2023
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Ingår i: Nature Neuroscience. - : NATURE PORTFOLIO. - 1097-6256 .- 1546-1726. ; 26, s. 1835-1836
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Bud Craig, an outstanding neuroscientist, died on 15 July 2023 at age 71. Bud made unique contributions to the fields of pain and interoception, challenging major dogmas and offering powerful explanations for various phenomena including central pain and the subjective awareness of feelings, with great implications for our understanding of consciousness.
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| 14. |
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| 18. |
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| 19. |
- Bulik, CM, et al.
(författare)
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Genetics and neurobiology of eating disorders
- 2022
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Ingår i: Nature neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 25:5, s. 543-554
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Tidskriftsartikel (refereegranskat)
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| 20. |
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| 21. |
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| 22. |
- Carlen, Marie, et al.
(författare)
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Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke
- 2009
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 12:3, s. 259-267
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Tidskriftsartikel (refereegranskat)abstract
- Neurons are continuously generated from stem cells in discrete regions in the adult mammalian brain. We found that ependymal cells lining the lateral ventricles were quiescent and did not contribute to adult neurogenesis under normal conditions in mice but instead gave rise to neuroblasts and astrocytes in response to stroke. Ependymal cell quiescence was actively maintained by canonical Notch signaling. Inhibition of this pathway in uninjured animals allowed ependymal cells to enter the cell cycle and produce olfactory bulb neurons, whereas forced Notch signaling was sufficient to block the ependymal cell response to stroke. Ependymal cells were depleted by stroke and failed to self-renew sufficiently to maintain their own population. Thus, although ependymal cells act as primary cells in the neural lineage to produce neurons and glial cells after stroke, they do not fulfill defining criteria for stem cells under these conditions and instead serve as a reservoir that is recruited by injury.
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| 23. |
- Chen, Fangyi, et al.
(författare)
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A differentially amplified motion in the ear for near-threshold sound detection
- 2011
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 14:6, s. 770-774
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Tidskriftsartikel (refereegranskat)abstract
- The ear is a remarkably sensitive pressure fluctuation detector. In guinea pigs, behavioral measurements indicate a minimum detectable sound pressure of ∼20 μPa at 16 kHz. Such faint sounds produce 0.1-nm basilar membrane displacements, a distance smaller than conformational transitions in ion channels. It seems that noise within the auditory system would swamp such tiny motions, making weak sounds imperceptible. Here we propose a new mechanism contributing to a resolution of this problem and validate it through direct measurement. We hypothesized that vibration at the apical side of hair cells is enhanced compared with that at the commonly measured basilar membrane side. Using in vivo optical coherence tomography, we demonstrated that apical-side vibrations peaked at a higher frequency, had different timing and were enhanced compared with those at the basilar membrane. These effects depend nonlinearly on the stimulus sound pressure level. The timing difference and enhancement of vibrations are important for explaining how the noise problem is circumvented.
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| 24. |
- Chowdhury, Rumana, et al.
(författare)
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Dopamine restores reward prediction errors in old age
- 2013
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 16:5, s. 648-653
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Tidskriftsartikel (refereegranskat)abstract
- Senescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum, measured by diffusion tensor imaging, was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults. This drug effect was linked to restoration of a canonical neural RPE. Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA.
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| 25. |
- Colombo, Gloria, et al.
(författare)
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A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes
- 2022
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Ingår i: Nature Neuroscience. - : Springer Nature. - 1097-6256 .- 1546-1726. ; 25:10, s. 1379-
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Tidskriftsartikel (refereegranskat)abstract
- Environmental cues influence the highly dynamic morphology of microglia. Strategies to characterize these changes usually involve user-selected morphometric features, which preclude the identification of a spectrum of context-dependent morphological phenotypes. Here we develop MorphOMICs, a topological data analysis approach, which enables semiautomatic mapping of microglial morphology into an atlas of cue-dependent phenotypes and overcomes feature-selection biases and biological variability. We extract spatially heterogeneous and sexually dimorphic morphological phenotypes for seven adult mouse brain regions. This sex-specific phenotype declines with maturation but increases over the disease trajectories in two neurodegeneration mouse models, with females showing a faster morphological shift in affected brain regions. Remarkably, microglia morphologies reflect an adaptation upon repeated exposure to ketamine anesthesia and do not recover to control morphologies. Finally, we demonstrate that both long primary processes and short terminal processes provide distinct insights to morphological phenotypes. MorphOMICs opens a new perspective to characterize microglial morphology.
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| 26. |
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| 27. |
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| 28. |
- Critchley, Hugo D, et al.
(författare)
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Neural systems supporting interoceptive awareness.
- 2004
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Ingår i: Nat Neurosci. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 7:2, s. 189-95
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Tidskriftsartikel (refereegranskat)abstract
- Influential theories of human emotion argue that subjective feeling states involve representation of bodily responses elicited by emotional events. Within this framework, individual differences in intensity of emotional experience reflect variation in sensitivity to internal bodily responses. We measured regional brain activity by functional magnetic resonance imaging (fMRI) during an interoceptive task wherein subjects judged the timing of their own heartbeats. We observed enhanced activity in insula, somatomotor and cingulate cortices. In right anterior insular/opercular cortex, neural activity predicted subjects' accuracy in the heartbeat detection task. Furthermore, local gray matter volume in the same region correlated with both interoceptive accuracy and subjective ratings of visceral awareness. Indices of negative emotional experience correlated with interoceptive accuracy across subjects. These findings indicate that right anterior insula supports a representation of visceral responses accessible to awareness, providing a substrate for subjective feeling states.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- El Manira, A, et al.
(författare)
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Switching gears in the spinal cord
- 2008
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Ingår i: Nature neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 11:12, s. 1367-1368
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 36. |
- Engblom, David, 1975-, et al.
(författare)
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Microsomal prostaglandin E synthase-1 is the central switch during immune-induced pyresis
- 2003
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 6:11, s. 1137-1138
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Tidskriftsartikel (refereegranskat)abstract
- We studied the febrile response in mice deficient in microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal isomerase expressed in cytokine-sensitive brain endothelial cells. These animals showed no fever and no central prostaglandin (PG) E2 synthesis after peripheral injection of bacterial-wall lipopolysaccharide, but their pyretic capacity in response to centrally administered PGE2 was intact. Our findings identify mPGES-1 as the central switch during immune-induced pyresis and as a target for the treatment of fever and other PGE2-dependent acute phase reactions elicited by the brain.
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| 37. |
- Escartin, C., et al.
(författare)
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Reactive astrocyte nomenclature, definitions, and future directions
- 2021
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 24, s. 312-325
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Tidskriftsartikel (refereegranskat)abstract
- Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions. Good-bad binary classifications fail to describe reactive astrocytes in CNS disorders. Here, 81 researchers reach consensus on widespread misconceptions and provide definitions and recommendations for future research on reactive astrocytes.
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| 38. |
- Filosa, Alessandro, et al.
(författare)
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Neuron-glia communication via EphA4/ephrin-A3 modulates LTP through glial glutamate transport
- 2009
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 12:10, s. 1285-1292
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Tidskriftsartikel (refereegranskat)abstract
- Astrocytes are critical participants in synapse development and function, but their role in synaptic plasticity is unclear. Eph receptors and their ephrin ligands have been suggested to regulate neuron-glia interactions, and EphA4-mediated ephrin reverse signaling is required for synaptic plasticity in the hippocampus. Here we show that long-term potentiation (LTP) at the CA3-CA1 synapse is modulated by EphA4 in the postsynaptic CA1 cell and by ephrin-A3, a ligand of EphA4 that is found in astrocytes. Lack of EphA4 increased the abundance of glial glutamate transporters, and ephrin-A3 modulated transporter currents in astrocytes. Pharmacological inhibition of glial glutamate transporters rescued the LTP defects in EphA4 (Epha4) and ephrin-A3 (Efna3) mutant mice. Transgenic overexpression of ephrin-A3 in astrocytes reduces glutamate transporter levels and produces focal dendritic swellings possibly caused by glutamate excitotoxicity. These results suggest that EphA4/ephrin-A3 signaling is a critical mechanism for astrocytes to regulate synaptic function and plasticity.
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| 39. |
- Floriddia, E, et al.
(författare)
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In conversation with Igor Adameyko
- 2024
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Ingår i: Nature neuroscience. - 1546-1726. ; 27:4, s. 601-605
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 40. |
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| 41. |
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| 42. |
- Freischmidt, Axel, et al.
(författare)
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Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia
- 2015
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 18:5, s. 631-
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.
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| 43. |
- Fridberger, Anders, 1966-, et al.
(författare)
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Sound-induced differential motion within the hearing organ
- 2003
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 6:5, s. 446-448
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Tidskriftsartikel (refereegranskat)abstract
- Hearing depends on the transformation of sound-induced basilar membrane vibration into deflection of stereocilia1 on the sensory hair cells, but the nature of these mechanical transformations is unclear. Using new techniques to visualize and measure sound-induced vibration deep inside the moving organ of Corti, we found that two functionally crucial structures, the basilar membrane and the reticular lamina, have different centers of rotation, leading to shearing motion and rapid deformation for the mechanoreceptive outer hair cells. Structural relations within the organ of Corti are much more dynamic than previously thought, which clarifies how outer hair cell molecular motors can have such a powerful effect.
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