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  • 1
    Online-Ressource
    Online-Ressource
    Site-directed MT1-MMP trafficking and surface insertion regulate AChR clustering and remodeling at developing NMJs
    eLife Sciences Publications, Ltd ; 2020
    In:  eLife Vol. 9 ( 2020-03-24)
    Details
    In: eLife, eLife Sciences Publications, Ltd, Vol. 9 ( 2020-03-24)
    Kurzfassung: Voluntary movement relies on skeletal muscle cells and nerve cells being able to communicate with one another. This communication occurs at a specialized region called the neuromuscular junction, or NMJ for short. These junctions are surrounded by a meshwork of proteins, known as the matrix, which structurally supports the nerve and muscle cells. Muscle cells contain proteins called acetylcholine receptors on their cell surface. When these receptors cluster together at the NMJ, this allows nerve cells to communicate with the muscle cell and tell the muscle to contract. However, these clusters can also form spontaneously without the help of nerve cells at regions away from the communication site. Alongside these spontaneous clusters of acetylcholine receptors are dynamic actin-enriched structures. These structures are responsible for releasing enzymes that digest the surrounding matrix and are commonly found in migrating cells. But as skeletal muscle cells do not migrate, it remained unclear what purpose these structures serve at the NMJ. Now, Chan et al. have used advanced microscopy techniques to show how these actin-enriched structures can help acetylcholine receptors cluster together at the site of communication between the nerve and muscle cells. The experiments showed that these structures direct a molecule called MT1-MMP to the muscle surface. This molecule then clears the surrounding matrix so that signals sent from the nerve can be effectively deposited at the narrow space between these two cells. When the muscle cells receive this initiating signal, acetylcholine receptors are recruited from the spontaneously formed clusters to the communication site, allowing the muscle to contract. When MT1-MMP was experimentally eliminated in mice, this disrupted the recruitment of acetylcholine receptors to the NMJ. Overall, these experiments help researchers understand how clearing the matrix between nerve and muscle cells contributes to the deposition of factors that build the communication site at developing NMJs. In the future this might help develop treatments for movement disorders caused by abnormalities that affect the clearing of matrix proteins in these junctions.
    Materialart: Online-Ressource
    ISSN: 2050-084X
    URL: Article
    DOI: 10.7554/eLife.54379
    Sprache: Englisch
    Verlag: eLife Sciences Publications, Ltd
    Publikationsdatum: 2020
    ZDB Id: 2687154-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
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    Severe Acute Respiratory Syndrome Coronavirus 2 Infects and Damages the Mature and Immature Olfactory Sensory Neurons of Hamsters
    Oxford University Press (OUP) ; 2021
    In:  Clinical Infectious Diseases Vol. 73, No. 2 ( 2021-07-15), p. e503-e512
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 73, No. 2 ( 2021-07-15), p. e503-e512
    Kurzfassung: Coronavirus disease 2019 (COVID-19) is primarily an acute respiratory tract infection. Distinctively, a substantial proportion of COVID-19 patients develop olfactory dysfunction. Especially in young patients, loss of smell can be the first or only symptom. The roles of inflammatory obstruction of the olfactory clefts, inflammatory cytokines affecting olfactory neuronal function, destruction of olfactory neurons or their supporting cells, and direct invasion of olfactory bulbs in causing olfactory dysfunction are uncertain. Methods We investigated the location for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the olfactory epithelium (OE) to the olfactory bulb in golden Syrian hamsters. Results After intranasal inoculation with SARS-CoV-2, inflammatory cell infiltration and proinflammatory cytokine/chemokine responses were detected in the nasal turbinate tissues. The responses peaked between 2 and 4 days postinfection, with the highest viral load detected at day 2 postinfection. In addition to the pseudo-columnar ciliated respiratory epithelial cells, SARS-CoV-2 viral antigens were also detected in the mature olfactory sensory neurons labeled by olfactory marker protein, in the less mature olfactory neurons labeled by neuron-specific class III β-tubulin at the more basal position, and in the sustentacular cells, resulting in apoptosis and severe destruction of the OE. During the entire course of infection, SARS-CoV-2 viral antigens were not detected in the olfactory bulb. Conclusions In addition to acute inflammation at the OE, infection of mature and immature olfactory neurons and the supporting sustentacular cells by SARS-CoV-2 may contribute to the unique olfactory dysfunction related to COVID-19, which is not reported with SARS-CoV-2.
    Materialart: Online-Ressource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciaa995
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 2002229-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
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    Antidepressant-like effects of transcorneal electrical stimulation in rat models
    Elsevier BV ; 2022
    In:  Brain Stimulation Vol. 15, No. 3 ( 2022-05), p. 843-856
    Details
    In: Brain Stimulation, Elsevier BV, Vol. 15, No. 3 ( 2022-05), p. 843-856
    Materialart: Online-Ressource
    ISSN: 1935-861X
    URL: Article
    DOI: 10.1016/j.brs.2022.05.018
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2022
    ZDB Id: 2404774-0
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  • 4
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    Long-range projections coordinate distributed brain-wide neural activity with a specific spatiotemporal profile
    Proceedings of the National Academy of Sciences ; 2016
    In:  Proceedings of the National Academy of Sciences Vol. 113, No. 51 ( 2016-12-20)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 51 ( 2016-12-20)
    Kurzfassung: One challenge in contemporary neuroscience is to achieve an integrated understanding of the large-scale brain-wide interactions, particularly the spatiotemporal patterns of neural activity that give rise to functions and behavior. At present, little is known about the spatiotemporal properties of long-range neuronal networks. We examined brain-wide neural activity patterns elicited by stimulating ventral posteromedial (VPM) thalamo-cortical excitatory neurons through combined optogenetic stimulation and functional MRI (fMRI). We detected robust optogenetically evoked fMRI activation bilaterally in primary visual, somatosensory, and auditory cortices at low (1 Hz) but not high frequencies (5–40 Hz). Subsequent electrophysiological recordings indicated interactions over long temporal windows across thalamo-cortical, cortico-cortical, and interhemispheric callosal projections at low frequencies. We further observed enhanced visually evoked fMRI activation during and after VPM stimulation in the superior colliculus, indicating that visual processing was subcortically modulated by low-frequency activity originating from VPM. Stimulating posteromedial complex thalamo-cortical excitatory neurons also evoked brain-wide blood-oxygenation-level–dependent activation, although with a distinct spatiotemporal profile. Our results directly demonstrate that low-frequency activity governs large-scale, brain-wide connectivity and interactions through long-range excitatory projections to coordinate the functional integration of remote brain regions. This low-frequency phenomenon contributes to the neural basis of long-range functional connectivity as measured by resting-state fMRI.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1616361113
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2016
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
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    Online-Ressource
    SOX9 and SOX10 control fluid homeostasis in the inner ear for hearing through independent and cooperative mechanisms
    Proceedings of the National Academy of Sciences ; 2022
    In:  Proceedings of the National Academy of Sciences Vol. 119, No. 46 ( 2022-11-15)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 119, No. 46 ( 2022-11-15)
    Kurzfassung: The in vivo mechanisms underlying dominant syndromes caused by mutations in SRY-Box Transcription Factor 9 ( SOX9 ) and SOX10 ( SOXE ) transcription factors, when they either are expressed alone or are coexpressed, are ill-defined. We created a mouse model for the campomelic dysplasia SOX9 Y440X mutation, which truncates the transactivation domain but leaves DNA binding and dimerization intact. Here, we find that SOX9 Y440X causes deafness via distinct mechanisms in the endolymphatic sac (ES)/duct and cochlea. By contrast, conditional heterozygous Sox9 -null mice are normal. During the ES development of Sox9 Y440X/+ heterozygotes, Sox10 and genes important for ionic homeostasis are down-regulated, and there is developmental persistence of progenitors, resulting in fewer mature cells. Sox10 heterozygous null mutants also display persistence of ES/duct progenitors. By contrast, SOX10 retains its expression in the early Sox9 Y440X/+ mutant cochlea. Later, in the postnatal stria vascularis, dominant interference by SOX9 Y440X is implicated in impairing the normal cooperation of SOX9 and SOX10 in repressing the expression of the water channel Aquaporin 3, thereby contributing to endolymphatic hydrops. Our study shows that for a functioning endolymphatic system in the inner ear, SOX9 regulates Sox10 , and depending on the cell type and target gene, it works either independently of or cooperatively with SOX10. SOX9 Y440X can interfere with the activity of both SOXE factors, exerting effects that can be classified as haploinsufficient/hypomorphic or dominant negative depending on the cell/gene context. This model of disruption of transcription factor partnerships may be applicable to congenital deafness, which affects ∼0.3% of newborns, and other syndromic disorders.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2122121119
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2022
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    Specific depletion of the motor protein KIF5B leads to deficits in dendritic transport, synaptic plasticity and memory
    eLife Sciences Publications, Ltd ; 2020
    In:  eLife Vol. 9 ( 2020-01-21)
    Details
    In: eLife, eLife Sciences Publications, Ltd, Vol. 9 ( 2020-01-21)
    Kurzfassung: Transporting molecules within a cell becomes a daunting task when the cell is a neuron, with fibers called axons and dendrites that can stretch as long as a meter. Neurons use many different molecules to send messages across the body and store memories in the brain. If the right molecules cannot be delivered along the length of nerve cells, connections to neighboring neurons may decay, which may impair learning and memory. Motor proteins are responsible for transporting molecules within cells. Kinesins are a type of motor protein that typically transports materials from the body of a neuron to the cell’s periphery, including the dendrites, which is where a neuron receives messages from other nerve cells. Each cell has up to 45 different kinesin motors, but it is not known whether each one performs a distinct task or if they have overlapping roles. Now, Zhao, Fok et al. have studied two similar kinesins, called KIF5A and KIF5B, in rodent neurons to determine their roles. First, it was shown that both proteins were found at dendritic spines, which are small outgrowths on dendrites where contact with other cells occurs. Next, KIF5A and KIF5B were depleted, one at a time, from neurons extracted from a brain region called the hippocampus. Removing KIF5B interfered with the formation of dendritic spines, but removing KIF5A did not have an effect. Dendritic spines are essential for learning and memory, so several behavioral tests were conducted on mice that had been genetically modified to express less KIF5B in the forebrain. These tests revealed that the mice performed poorly in tasks that tested their memory recall. This work opens a new area of research studying the specific roles of different kinesin motor proteins in nerve cells. This could have important implications because certain kinesin motor proteins such as KIF5A are known to be defective in some inherited neurodegenerative diseases.
    Materialart: Online-Ressource
    ISSN: 2050-084X
    URL: Article
    DOI: 10.7554/eLife.53456
    Sprache: Englisch
    Verlag: eLife Sciences Publications, Ltd
    Publikationsdatum: 2020
    ZDB Id: 2687154-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
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    Online-Ressource
    Low-frequency hippocampal–cortical activity drives brain-wide resting-state functional MRI connectivity
    Proceedings of the National Academy of Sciences ; 2017
    In:  Proceedings of the National Academy of Sciences Vol. 114, No. 33 ( 2017-08-15)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 114, No. 33 ( 2017-08-15)
    Kurzfassung: The hippocampus, including the dorsal dentate gyrus (dDG), and cortex engage in bidirectional communication. We propose that low-frequency activity in hippocampal–cortical pathways contributes to brain-wide resting-state connectivity to integrate sensory information. Using optogenetic stimulation and brain-wide fMRI and resting-state fMRI (rsfMRI), we determined the large-scale effects of spatiotemporal-specific downstream propagation of hippocampal activity. Low-frequency (1 Hz), but not high-frequency (40 Hz), stimulation of dDG excitatory neurons evoked robust cortical and subcortical brain-wide fMRI responses. More importantly, it enhanced interhemispheric rsfMRI connectivity in various cortices and hippocampus. Subsequent local field potential recordings revealed an increase in slow oscillations in dorsal hippocampus and visual cortex, interhemispheric visual cortical connectivity, and hippocampal–cortical connectivity. Meanwhile, pharmacological inactivation of dDG neurons decreased interhemispheric rsfMRI connectivity. Functionally, visually evoked fMRI responses in visual regions also increased during and after low-frequency dDG stimulation. Together, our results indicate that low-frequency activity robustly propagates in the dorsal hippocampal–cortical pathway, drives interhemispheric cortical rsfMRI connectivity, and mediates visual processing.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1703309114
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2017
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
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    Optogenetic fMRI interrogation of brain-wide central vestibular pathways
    Proceedings of the National Academy of Sciences ; 2019
    In:  Proceedings of the National Academy of Sciences Vol. 116, No. 20 ( 2019-05-14), p. 10122-10129
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 20 ( 2019-05-14), p. 10122-10129
    Kurzfassung: Blood oxygen level-dependent functional MRI (fMRI) constitutes a powerful neuroimaging technology to map brain-wide functions in response to specific sensory or cognitive tasks. However, fMRI mapping of the vestibular system, which is pivotal for our sense of balance, poses significant challenges. Physical constraints limit a subject’s ability to perform motion- and balance-related tasks inside the scanner, and current stimulation techniques within the scanner are nonspecific to delineate complex vestibular nucleus (VN) pathways. Using fMRI, we examined brain-wide neural activity patterns elicited by optogenetically stimulating excitatory neurons of a major vestibular nucleus, the ipsilateral medial VN (MVN). We demonstrated robust optogenetically evoked fMRI activations bilaterally at sensorimotor cortices and their associated thalamic nuclei (auditory, visual, somatosensory, and motor), high-order cortices (cingulate, retrosplenial, temporal association, and parietal), and hippocampal formations (dentate gyrus, entorhinal cortex, and subiculum). We then examined the modulatory effects of the vestibular system on sensory processing using auditory and visual stimulation in combination with optogenetic excitation of the MVN. We found enhanced responses to sound in the auditory cortex, thalamus, and inferior colliculus ipsilateral to the stimulated MVN. In the visual pathway, we observed enhanced responses to visual stimuli in the ipsilateral visual cortex, thalamus, and contralateral superior colliculus. Taken together, our imaging findings reveal multiple brain-wide central vestibular pathways. We demonstrate large-scale modulatory effects of the vestibular system on sensory processing.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1812453116
    RVK:
    TA 1000
    RVK:
    WA 15000
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2019
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
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    Online-Ressource
    GABA-B receptor activation in the rat globus pallidus potently suppresses pentylenetetrazol-induced tonic seizures
    Springer Science and Business Media LLC ; 2004
    In:  Journal of Biomedical Science Vol. 11, No. 4 ( 2004-7), p. 457-464
    Details
    In: Journal of Biomedical Science, Springer Science and Business Media LLC, Vol. 11, No. 4 ( 2004-7), p. 457-464
    Materialart: Online-Ressource
    ISSN: 1021-7770 , 1423-0127
    URL: Article
    DOI: 10.1007/BF02256094
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2004
    ZDB Id: 1482918-6
    ZDB Id: 1193378-1
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
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    Online-Ressource
    Genipin-treated chitosan nanofibers as a novel scaffold for nerve guidance channel design
    Elsevier BV ; 2018
    In:  Colloids and Surfaces B: Biointerfaces Vol. 162 ( 2018-02), p. 126-134
    Details
    In: Colloids and Surfaces B: Biointerfaces, Elsevier BV, Vol. 162 ( 2018-02), p. 126-134
    Materialart: Online-Ressource
    ISSN: 0927-7765
    URL: Article
    DOI: 10.1016/j.colsurfb.2017.11.061
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2018
    ZDB Id: 1500523-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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