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  1. Article ; Online: Circuit formation in the adult brain.

    Seng, Charlotte / Luo, Wenshu / Földy, Csaba

    The European journal of neuroscience

    2022  Volume 56, Issue 3, Page(s) 4187–4213

    Abstract: Neurons in the mammalian central nervous system display an enormous capacity for circuit formation during development but not later in life. In principle, new circuits could be also formed in adult brain, but the absence of the developmental milieu and ... ...

    Abstract Neurons in the mammalian central nervous system display an enormous capacity for circuit formation during development but not later in life. In principle, new circuits could be also formed in adult brain, but the absence of the developmental milieu and the presence of growth inhibition and hundreds of working circuits are generally viewed as unsupportive for such a process. Here, we bring together evidence from different areas of neuroscience-such as neurological disorders, adult-brain neurogenesis, innate behaviours, cell grafting, and in vivo cell reprogramming-which demonstrates robust circuit formation in adult brain. In some cases, adult-brain rewiring is ongoing and required for certain types of behaviour and memory, while other cases show significant promise for brain repair in disease models. Together, these examples highlight that the adult brain has higher capacity for structural plasticity than previously recognized. Understanding the underlying mechanisms behind this retained plasticity has the potential to advance basic knowledge regarding the molecular organization of synaptic circuits and could herald a new era of neural circuit engineering for therapeutic repair.
    MeSH term(s) Adult ; Animals ; Brain/physiology ; Humans ; Mammals ; Nervous System Diseases ; Neurogenesis/physiology ; Neuronal Plasticity/physiology ; Neurons/physiology
    Language English
    Publishing date 2022-07-01
    Publishing country France
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/ejn.15742
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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: Transcriptomically-Guided Pharmacological Experiments in Neocortical and Hippocampal NPY-Positive GABAergic Interneurons.

    Beerens, Sanne / Winterer, Jochen / Lukacsovich, David / Földy, Csaba / Wozny, Christian

    eNeuro

    2022  Volume 9, Issue 2

    Abstract: Cortical GABAergic interneurons have been shown to fulfil important roles by inhibiting excitatory principal neurons. Recent transcriptomic studies have confirmed seminal discoveries that used anatomic and electrophysiological methods highlighting the ... ...

    Abstract Cortical GABAergic interneurons have been shown to fulfil important roles by inhibiting excitatory principal neurons. Recent transcriptomic studies have confirmed seminal discoveries that used anatomic and electrophysiological methods highlighting the existence of multiple different classes of GABAergic interneurons. Although some of these studies have emphasized that inter-regional differences may exist for a given class, the extent of such differences remains unknown. To address this problem, we used single-cell Patch-RNAseq to characterize neuropeptide Y (NPY)-positive GABAergic interneurons in superficial layers of the primary auditory cortex (AC) and in distal layers of area CA3 in mice. We found that more than 300 genes are differentially expressed in NPY-positive neurons between these two brain regions. For example, the AMPA receptor (AMPAR) auxiliary subunit Shisa9/CKAMP44 and the 5HT2a receptor (5HT2aR) are significantly higher expressed in auditory NPY-positive neurons. These findings guided us to perform pharmacological experiments that revealed a role for 5HT2aRs in auditory NPY-positive neurons. Specifically, although the application of 5HT led to a depolarization of both auditory and CA3 NPY-positive neurons, the 5HT2aR antagonist ketanserin only reversed membrane potential changes in auditory NPY-positive neurons. Our study demonstrates the potential of single-cell transcriptomic studies in guiding directed pharmacological experiments.
    MeSH term(s) Animals ; Hippocampus/metabolism ; Interneurons/physiology ; Mice ; Neocortex/metabolism ; Neurons/metabolism ; Neuropeptide Y/metabolism
    Chemical Substances Neuropeptide Y
    Language English
    Publishing date 2022-04-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2800598-3
    ISSN 2373-2822 ; 2373-2822
    ISSN (online) 2373-2822
    ISSN 2373-2822
    DOI 10.1523/ENEURO.0005-22.2022
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  3. Article ; Online: Transcriptional and morphological profiling of parvalbumin interneuron subpopulations in the mouse hippocampus.

    Que, Lin / Lukacsovich, David / Luo, Wenshu / Földy, Csaba

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 108

    Abstract: The diversity reflected by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this ... ...

    Abstract The diversity reflected by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this hypothesis, but a lack of morphological information has limited the identification of several known cell types. In this study, we used single-cell RNA-seq in morphologically identified parvalbumin interneurons (PV-INs), and studied their transcriptomic states in the morphological, physiological, and developmental domains. Overall, we find high transcriptomic similarity among PV-INs, with few genes showing divergent expression between morphologically different types. Furthermore, PV-INs show a uniform synaptic cell adhesion molecule (CAM) profile, suggesting that CAM expression in mature PV cells does not reflect wiring specificity after development. Together, our results suggest that while PV-INs differ in anatomy and in vivo activity, their continuous transcriptomic and homogenous biophysical landscapes are not predictive of these distinct identities.
    MeSH term(s) Aging/genetics ; Animals ; Cell Adhesion Molecules/metabolism ; Cell Differentiation/genetics ; Electrophysiological Phenomena ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Hemoglobins/genetics ; Hemoglobins/metabolism ; Hippocampus/cytology ; Interneurons/cytology ; Interneurons/metabolism ; Male ; Mice ; Parvalbumins/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Transcriptome/genetics
    Chemical Substances Cell Adhesion Molecules ; Hemoglobins ; Parvalbumins ; RNA, Messenger
    Language English
    Publishing date 2021-01-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-20328-4
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  4. Article ; Online: Transcriptional and morphological profiling of parvalbumin interneuron subpopulations in the mouse hippocampus

    Lin Que / David Lukacsovich / Wenshu Luo / Csaba Földy

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 15

    Abstract: The relationship between gene expression and morphology to classify PV interneurons is unclear. Here, the authors show transcriptional continuity of morphologically distinct mouse hippocampal PV interneurons subtypes, combining single-cell RNA sequencing ...

    Abstract The relationship between gene expression and morphology to classify PV interneurons is unclear. Here, the authors show transcriptional continuity of morphologically distinct mouse hippocampal PV interneurons subtypes, combining single-cell RNA sequencing and electrophysiology.
    Keywords Science ; Q
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Gephyrin phosphorylation facilitates sexually dimorphic development and function of parvalbumin interneurons in the mouse hippocampus.

    Campbell, Benjamin F N / Cruz-Ochoa, Natalia / Otomo, Kanako / Lukacsovich, David / Espinosa, Pedro / Abegg, Andrin / Luo, Wenshu / Bellone, Camilla / Földy, Csaba / Tyagarajan, Shiva K

    Molecular psychiatry

    2024  

    Abstract: The precise function of specialized GABAergic interneuron subtypes is required to provide appropriate synaptic inhibition for regulating principal neuron excitability and synchronization within brain circuits. Of these, parvalbumin-type (PV neuron) ... ...

    Abstract The precise function of specialized GABAergic interneuron subtypes is required to provide appropriate synaptic inhibition for regulating principal neuron excitability and synchronization within brain circuits. Of these, parvalbumin-type (PV neuron) dysfunction is a feature of several sex-biased psychiatric and brain disorders, although, the underlying developmental mechanisms are unclear. While the transcriptional action of sex hormones generates sexual dimorphism during brain development, whether kinase signaling contributes to sex differences in PV neuron function remains unexplored. In the hippocampus, we report that gephyrin, the main inhibitory post-synaptic scaffolding protein, is phosphorylated at serine S268 and S270 in a developmentally-dependent manner in both males and females. When examining Gphn
    Language English
    Publishing date 2024-03-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 1330655-8
    ISSN 1476-5578 ; 1359-4184
    ISSN (online) 1476-5578
    ISSN 1359-4184
    DOI 10.1038/s41380-024-02517-5
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4812: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Commissural dentate granule cell projections and their rapid formation in the adult brain.

    Egger, Matteo / Luo, Wenshu / Cruz-Ochoa, Natalia / Lukacsovich, David / Varga, Csaba / Que, Lin / Maloveczky, Gyula / Winterer, Jochen / Kaur, Rashmit / Lukacsovich, Tamás / Földy, Csaba

    PNAS nexus

    2023  Volume 2, Issue 4, Page(s) pgad088

    Abstract: Dentate granule cells (GCs) have been characterized as unilaterally projecting neurons within each hippocampus. Here, we describe a unique class, the commissural GCs, which atypically project to the contralateral hippocampus in mice. Although commissural ...

    Abstract Dentate granule cells (GCs) have been characterized as unilaterally projecting neurons within each hippocampus. Here, we describe a unique class, the commissural GCs, which atypically project to the contralateral hippocampus in mice. Although commissural GCs are rare in the healthy brain, their number and contralateral axon density rapidly increase in a rodent model of temporal lobe epilepsies. In this model, commissural GC axon growth appears together with the well-studied hippocampal mossy fiber sprouting and may be important for the pathomechanisms of epilepsy. Our results augment the current view on hippocampal GC diversity and demonstrate powerful activation of a commissural wiring program in the adult brain.
    Language English
    Publishing date 2023-03-20
    Publishing country England
    Document type Journal Article
    ISSN 2752-6542
    ISSN (online) 2752-6542
    DOI 10.1093/pnasnexus/pgad088
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  7. Article: Deep Survey of GABAergic Interneurons: Emerging Insights From Gene-Isoform Transcriptomics.

    Que, Lin / Winterer, Jochen / Földy, Csaba

    Frontiers in molecular neuroscience

    2019  Volume 12, Page(s) 115

    Abstract: GABAergic interneuron diversity is a key feature in the brain that helps to create different brain activity patterns and behavioral states. Cell type classification schemes-based on anatomical, physiological and molecular features-have provided us with a ...

    Abstract GABAergic interneuron diversity is a key feature in the brain that helps to create different brain activity patterns and behavioral states. Cell type classification schemes-based on anatomical, physiological and molecular features-have provided us with a detailed understanding of the distinct types that constitute this diversity and their contribution to brain function. Over recent years, the utility of single-cell RNAseq has majorly complemented this existing framework, vastly expanding our knowledge base, particularly regarding molecular features. Single-cell gene-expression profiles of tens of thousands of GABAergic cells from many different types are now available. The analysis of these data has shed new lights onto previous classification principles and illuminates a path towards a deeper understanding of molecular hallmarks behind interneuron diversity. A large part of such molecular features is synapse-related. These include ion channels and receptors, as well as key synaptic organizers and trans-synaptic signaling molecules. Increasing evidence suggests that transcriptional and post-transcriptional modifications further diversify these molecules and generate cell type-specific features. Thus, unraveling the cell type-specific nature of gene-isoform expression will be a key in cell type classification. This review article discusses progress in the transcriptomic survey of interneurons and insights that have begun to manifest from isoform-level analyses.
    Language English
    Publishing date 2019-05-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2019.00115
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  8. Article: Pcdh11x

    Luo, Wenshu / Cruz-Ochoa, Natalia Andrea / Seng, Charlotte / Egger, Matteo / Lukacsovich, David / Lukacsovich, Tamás / Földy, Csaba

    Frontiers in neuroscience

    2022  Volume 16, Page(s) 888362

    Abstract: Circuit formation is a defining characteristic of the developing brain. However, multiple lines of evidence suggest that circuit formation can also take place in adults, the mechanisms of which remain poorly understood. Here, we investigated the epilepsy- ...

    Abstract Circuit formation is a defining characteristic of the developing brain. However, multiple lines of evidence suggest that circuit formation can also take place in adults, the mechanisms of which remain poorly understood. Here, we investigated the epilepsy-associated mossy fiber (MF) sprouting in the adult hippocampus and asked which cell surface molecules define its target specificity. Using single-cell RNAseq data, we found lack and expression of
    Language English
    Publishing date 2022-09-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2022.888362
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  9. Article ; Online: Neurexin-3 defines synapse- and sex-dependent diversity of GABAergic inhibition in ventral subiculum.

    Boxer, Emma E / Seng, Charlotte / Lukacsovich, David / Kim, JungMin / Schwartz, Samantha / Kennedy, Matthew J / Földy, Csaba / Aoto, Jason

    Cell reports

    2021  Volume 37, Issue 10, Page(s) 110098

    Abstract: Ventral subiculum (vSUB) is integral to the regulation of stress and reward; however, the intrinsic connectivity and synaptic properties of the inhibitory local circuit are poorly understood. Neurexin-3 (Nrxn3) is highly expressed in hippocampal ... ...

    Abstract Ventral subiculum (vSUB) is integral to the regulation of stress and reward; however, the intrinsic connectivity and synaptic properties of the inhibitory local circuit are poorly understood. Neurexin-3 (Nrxn3) is highly expressed in hippocampal inhibitory neurons, but its function at inhibitory synapses has remained elusive. Using slice electrophysiology, imaging, and single-cell RNA sequencing, we identify multiple roles for Nrxn3 at GABAergic parvalbumin (PV) interneuron synapses made onto vSUB regular-spiking (RS) and burst-spiking (BS) principal neurons. Surprisingly, we find that intrinsic connectivity of vSUB and synaptic function of Nrxn3 in vSUB are sexually dimorphic. We reveal that PVs make preferential contact with RS neurons in male mice, but BS neurons in female mice. Furthermore, we determine that despite comparable Nrxn3 isoform expression in male and female PV neurons, Nrxn3 knockout impairs synapse density, postsynaptic strength, and inhibitory postsynaptic current (IPSC) amplitude at PV-RS synapses in males, but enhances presynaptic release and IPSC amplitude in females.
    MeSH term(s) Animals ; Female ; GABAergic Neurons/metabolism ; Hippocampus/metabolism ; Inhibitory Postsynaptic Potentials ; Interneurons/metabolism ; Male ; Mice, Knockout ; Nerve Tissue Proteins/metabolism ; Neural Inhibition ; Parvalbumins/genetics ; Parvalbumins/metabolism ; Presynaptic Terminals/metabolism ; Sex Characteristics ; Mice
    Chemical Substances Nerve Tissue Proteins ; Parvalbumins ; neurexin 3, mouse
    Language English
    Publishing date 2021-12-07
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2021.110098
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  10. Article ; Online: Single-Cell RNA-Seq Reveals Developmental Origins and Ontogenetic Stability of Neurexin Alternative Splicing Profiles.

    Lukacsovich, David / Winterer, Jochen / Que, Lin / Luo, Wenshu / Lukacsovich, Tamas / Földy, Csaba

    Cell reports

    2019  Volume 27, Issue 13, Page(s) 3752–3759.e4

    Abstract: Neurexins are key synaptic organizers that are expressed in thousands of alternatively spliced isoforms. Because transsynaptic neurexin interactions with different postsynaptic molecules are largely isoform dependent, a cell type-level census of ... ...

    Abstract Neurexins are key synaptic organizers that are expressed in thousands of alternatively spliced isoforms. Because transsynaptic neurexin interactions with different postsynaptic molecules are largely isoform dependent, a cell type-level census of different neurexin isoforms could predict molecular interactions relating to synapse identity and function. Using single-cell transcriptomics to study the origin of neurexin diversity in multiple murine mature and embryonic cell types, we have discovered shared neurexin expression patterns in developmentally related cells. By comparing neurexin profiles in immature embryonic neurons, we show that neurexin profiles are specified during early development and remain unchanged throughout neuronal maturation. Thus, our findings reveal ontogenetic stability and provide a cell type-level census of neurexin isoform expression in the cortex.
    MeSH term(s) Alternative Splicing ; Animals ; Cerebral Cortex/cytology ; Cerebral Cortex/metabolism ; Female ; Male ; Mice ; Neural Cell Adhesion Molecules/biosynthesis ; Neural Cell Adhesion Molecules/genetics ; Optogenetics ; Protein Stability ; RNA-Seq ; Single-Cell Analysis
    Chemical Substances Neural Cell Adhesion Molecules
    Language English
    Publishing date 2019-06-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2019.05.090
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