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  1. Article ; Online: Structural arrangement of auditory brainstem nuclei in the bats Phyllostomus discolor and Carollia perspicillata.

    Pätz, Christina / Console-Meyer, Laura / Felmy, Felix

    The Journal of comparative neurology

    2022  Volume 530, Issue 15, Page(s) 2762–2781

    Abstract: The structure of the mammalian auditory brainstem is evolutionarily highly plastic, and distinct nuclei arrange in a species-dependent manner. Such anatomical variability is present in the superior olivary complex (SOC) and the nuclei of the lateral ... ...

    Abstract The structure of the mammalian auditory brainstem is evolutionarily highly plastic, and distinct nuclei arrange in a species-dependent manner. Such anatomical variability is present in the superior olivary complex (SOC) and the nuclei of the lateral lemniscus (LL). Due to the structure-function relationship in the auditory brainstem, the identification of individual nuclei supports the understanding of sound processing. Here, we comparatively describe the nucleus arrangement and the expression of functional markers in the auditory brainstem of the two bat species Phyllostomus discolor and Carollia perspicillata. Using immunofluorescent labeling, we describe the arrangement and identity of the SOC and LL nuclei based on the expression of synaptic markers (vesicular glutamate transporter 1 and glycine transporter 2), calcium-binding proteins, as well as the voltage-gated ion channel subunits Kv1.1 and HCN1. The distribution of excitatory and inhibitory synaptic labeling appears similar between both species and matches with that of other mammals. The detection of calcium-binding proteins indicates species-dependent differences and deviations from other mammals. Kv1.1 and HCN1 show largely the same expression pattern in both species, which diverges from other mammals, indicating functional adaptations in the cellular physiology of bat neurons.
    MeSH term(s) Animals ; Auditory Pathways/physiology ; Brain Stem/metabolism ; Calcium-Binding Proteins/metabolism ; Chiroptera/metabolism ; Inferior Colliculi/metabolism ; Olivary Nucleus/metabolism ; Superior Olivary Complex
    Chemical Substances Calcium-Binding Proteins
    Language English
    Publishing date 2022-06-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3086-7
    ISSN 1096-9861 ; 0021-9967 ; 0092-7317
    ISSN (online) 1096-9861
    ISSN 0021-9967 ; 0092-7317
    DOI 10.1002/cne.25355
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Developmental Easing of Short-Term Depression in "Winner" Climbing Fibers.

    Pätz, Christina / Brachtendorf, Simone / Eilers, Jens

    Frontiers in cellular neuroscience

    2019  Volume 13, Page(s) 183

    Abstract: The postnatal development of cerebellar climbing fiber (CF) to Purkinje neuron (PN) synapses is characterized by a substantial pruning during the first 3 weeks after birth, switching from multiple- to single-CF innervation. Previous studies suggested ... ...

    Abstract The postnatal development of cerebellar climbing fiber (CF) to Purkinje neuron (PN) synapses is characterized by a substantial pruning during the first 3 weeks after birth, switching from multiple- to single-CF innervation. Previous studies suggested that CF maturation is governed by bidirectional changes of synaptic plasticity. The strengthening of surviving "winner" CFs, which translocate from the PN soma to the dendrite, is thought to be guided by long-term potentiation (LTP), while weakening of to-be-eliminated "loser" CFs, which remain on the soma, was proposed to be due to long-term depression (LTD). However, there are conflicting results from previous studies, whether or not strengthening of winner and weakening of loser CFs during postnatal development is accompanied by changes in short-term plasticity and, thus, whether pre- or postsynaptic forms of LTD and LTP are operational. We, therefore, analyzed the developmental profile of paired-pulse depression (PPD) in "weak" and "strong" CFs in 3-21-day old
    Language English
    Publishing date 2019-05-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2019.00183
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Undisturbed climbing fiber pruning in the cerebellar cortex of CX

    Kaiser, Nicole / Pätz, Christina / Brachtendorf, Simone / Eilers, Jens / Bechmann, Ingo

    Glia

    2020  Volume 68, Issue 11, Page(s) 2316–2329

    Abstract: Pruning, the elimination of excess synapses is a phenomenon of fundamental importance for correct wiring of the central nervous system. The establishment of the cerebellar climbing fiber (CF)-to-Purkinje cell (PC) synapse provides a suitable model to ... ...

    Abstract Pruning, the elimination of excess synapses is a phenomenon of fundamental importance for correct wiring of the central nervous system. The establishment of the cerebellar climbing fiber (CF)-to-Purkinje cell (PC) synapse provides a suitable model to study pruning and pruning-relevant processes during early postnatal development. Until now, the role of microglia in pruning remains under intense investigation. Here, we analyzed migration of microglia into the cerebellar cortex during early postnatal development and their possible contribution to the elimination of CF-to-PC synapses. Microglia enrich in the PC layer at pruning-relevant time points giving rise to the possibility that microglia are actively involved in synaptic pruning. We investigated the contribution of microglial fractalkine (CX
    MeSH term(s) Animals ; Axons/metabolism ; Cerebellum/metabolism ; Chemokine CX3CL1/metabolism ; Mice ; Purkinje Cells ; Synapses/metabolism
    Chemical Substances Chemokine CX3CL1
    Language English
    Publishing date 2020-06-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639414-0
    ISSN 1098-1136 ; 0894-1491
    ISSN (online) 1098-1136
    ISSN 0894-1491
    DOI 10.1002/glia.23842
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The transgenic mouse line Igsf9-eGFP allows targeted stimulation of inferior olive efferents.

    Pätz, Christina / Brachtendorf, Simone / Eilers, Jens

    Journal of neuroscience methods

    2017  Volume 296, Page(s) 84–92

    Abstract: Background: The inferior olive (IO) innervates the cerebellum forming synapses in the deep cerebellar nuclei (DCN) and the cerebellar cortex. Beside the well-known exception of synapses on Purkinje neurons, synapses between IO efferents and other ... ...

    Abstract Background: The inferior olive (IO) innervates the cerebellum forming synapses in the deep cerebellar nuclei (DCN) and the cerebellar cortex. Beside the well-known exception of synapses on Purkinje neurons, synapses between IO efferents and other neuronal targets have not been studied intensively, mostly due to the technical challenge of unequivocally identifying IO efferents in electrophysiological experiments.
    New method: We describe the transgenic mouse line Igsf9-eGFP, which expresses GFP in IO neurons, as a suitable tool for studying IO efferents using live imaging, immunohistochemistry and electrophysiology.
    Results: In the Igsf9-eGFP line, GFP-positive neurons are found in all IO subnuclei. Their efferents show the expected trajectories innervating the DCN and, as climbing fibers (CFs), the cerebellar cortex. In the DCN the dentate nucleus shows the strongest innervation, and, within the cerebellar cortex, CFs show a rostral-to-caudal gradient. GFP-positive CFs undergo a normal postnatal maturation, and evoke normal synaptic responses in Purkinje neurons and DCN neurons.
    Comparison with existing methods: IO efferents have been labelled via anterograde labelling, viral transfection and in transgenic mouse lines. The latter approach does not require stereotactic injections. However, available mouse lines show only a sparse GFP expression, harbor GFP-positive axons of other cerebellar fibers, or have not been characterized in detail.
    Conclusions: The Igsf9-eGFP line is characterized by a moderate density of GFP-positive IO efferents, which can be visually targeted for extracellular stimulation with micrometer precision. The mouse line will allow studying fiber-specific responses in all neurons targeted by the IO.
    MeSH term(s) Animals ; Cerebellum/cytology ; Cerebellum/growth & development ; Cerebellum/physiology ; Efferent Pathways/cytology ; Efferent Pathways/growth & development ; Efferent Pathways/physiology ; Excitatory Postsynaptic Potentials ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Immunoglobulins/genetics ; Immunoglobulins/metabolism ; Immunohistochemistry ; Mice, Transgenic ; Microscopy, Confocal ; Models, Animal ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neural Pathways/physiology ; Neurons, Efferent/cytology ; Neurons, Efferent/physiology ; Olivary Nucleus/cytology ; Olivary Nucleus/growth & development ; Olivary Nucleus/physiology ; Optical Imaging ; Patch-Clamp Techniques ; Tissue Culture Techniques
    Chemical Substances Igsf9 protein, mouse ; Immunoglobulins ; Nerve Tissue Proteins ; enhanced green fluorescent protein ; Green Fluorescent Proteins (147336-22-9)
    Language English
    Publishing date 2017-12-30
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 282721-9
    ISSN 1872-678X ; 0165-0270
    ISSN (online) 1872-678X
    ISSN 0165-0270
    DOI 10.1016/j.jneumeth.2017.12.024
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: DEAD-box RNA helicase Dbp4/DDX10 is an enhancer of α-synuclein toxicity and oligomerization.

    Popova, Blagovesta / Wang, Dan / Pätz, Christina / Akkermann, Dagmar / Lázaro, Diana F / Galka, Dajana / Kolog Gulko, Miriam / Bohnsack, Markus T / Möbius, Wiebke / Bohnsack, Katherine E / Outeiro, Tiago F / Braus, Gerhard H

    PLoS genetics

    2021  Volume 17, Issue 3, Page(s) e1009407

    Abstract: Parkinson's disease is a neurodegenerative disorder associated with misfolding and aggregation of α-synuclein as a hallmark protein. Two yeast strain collections comprising conditional alleles of essential genes were screened for the ability of each ... ...

    Abstract Parkinson's disease is a neurodegenerative disorder associated with misfolding and aggregation of α-synuclein as a hallmark protein. Two yeast strain collections comprising conditional alleles of essential genes were screened for the ability of each allele to reduce or improve yeast growth upon α-synuclein expression. The resulting 98 novel modulators of α-synuclein toxicity clustered in several major categories including transcription, rRNA processing and ribosome biogenesis, RNA metabolism and protein degradation. Furthermore, expression of α-synuclein caused alterations in pre-rRNA transcript levels in yeast and in human cells. We identified the nucleolar DEAD-box helicase Dbp4 as a prominent modulator of α-synuclein toxicity. Downregulation of DBP4 rescued cells from α-synuclein toxicity, whereas overexpression led to a synthetic lethal phenotype. We discovered that α-synuclein interacts with Dbp4 or its human ortholog DDX10, sequesters the protein outside the nucleolus in yeast and in human cells, and stabilizes a fraction of α-synuclein oligomeric species. These findings provide a novel link between nucleolar processes and α-synuclein mediated toxicity with DDX10 emerging as a promising drug target.
    MeSH term(s) Amyloid/metabolism ; Amyloid/ultrastructure ; DEAD-box RNA Helicases/metabolism ; Gene Expression Regulation ; Humans ; Inclusion Bodies/metabolism ; Inclusion Bodies/pathology ; Models, Biological ; Neurodegenerative Diseases/etiology ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Protein Aggregates ; Protein Aggregation, Pathological/metabolism ; Protein Binding ; Protein Multimerization ; Protein Transport ; Yeasts/genetics ; Yeasts/metabolism ; alpha-Synuclein/chemistry ; alpha-Synuclein/genetics ; alpha-Synuclein/metabolism
    Chemical Substances Amyloid ; Protein Aggregates ; alpha-Synuclein ; DDX10 protein, human (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13)
    Language English
    Publishing date 2021-03-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1009407
    Database MEDical Literature Analysis and Retrieval System OnLINE

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