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  1. Article: Exploring the Importance of Environmental Complexity for Newly Hatched Zebrafish.

    Santacà, Maria / Gatto, Elia / Dadda, Marco / Bruzzone, Matteo / Dal Maschio, Marco / Bisazza, Angelo

    Animals : an open access journal from MDPI

    2024  Volume 14, Issue 7

    Abstract: The effects of an early impoverished social or physical environment on vertebrate neural development and cognition has been known for decades. While existing studies have focused on the long-term effects, measuring adult cognitive phenotypes, studies on ... ...

    Abstract The effects of an early impoverished social or physical environment on vertebrate neural development and cognition has been known for decades. While existing studies have focused on the long-term effects, measuring adult cognitive phenotypes, studies on the effects of environmental complexity on the early stages of development are lacking. Zebrafish (
    Language English
    Publishing date 2024-03-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606558-7
    ISSN 2076-2615
    ISSN 2076-2615
    DOI 10.3390/ani14071031
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  2. Article ; Online: Optogenetic Methods to Investigate Brain Alterations in Preclinical Models.

    Brondi, Marco / Bruzzone, Matteo / Lodovichi, Claudia / Dal Maschio, Marco

    Cells

    2022  Volume 11, Issue 11

    Abstract: Investigating the neuronal dynamics supporting brain functions and understanding how the alterations in these mechanisms result in pathological conditions represents a fundamental challenge. Preclinical research on model organisms allows for a multiscale ...

    Abstract Investigating the neuronal dynamics supporting brain functions and understanding how the alterations in these mechanisms result in pathological conditions represents a fundamental challenge. Preclinical research on model organisms allows for a multiscale and multiparametric analysis in vivo of the neuronal mechanisms and holds the potential for better linking the symptoms of a neurological disorder to the underlying cellular and circuit alterations, eventually leading to the identification of therapeutic/rescue strategies. In recent years, brain research in model organisms has taken advantage, along with other techniques, of the development and continuous refinement of methods that use light and optical approaches to reconstruct the activity of brain circuits at the cellular and system levels, and to probe the impact of the different neuronal components in the observed dynamics. These tools, combining low-invasiveness of optical approaches with the power of genetic engineering, are currently revolutionizing the way, the scale and the perspective of investigating brain diseases. The aim of this review is to describe how brain functions can be investigated with optical approaches currently available and to illustrate how these techniques have been adopted to study pathological alterations of brain physiology.
    MeSH term(s) Brain/pathology ; Humans ; Nervous System Diseases/genetics ; Neurons/pathology ; Optogenetics/methods
    Language English
    Publishing date 2022-06-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11111848
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  3. Article ; Online: Mucopolysaccharidosis type II zebrafish model exhibits early impaired proteasomal-mediated degradation of the axon guidance receptor Dcc.

    Manzoli, Rosa / Badenetti, Lorenzo / Bruzzone, Matteo / Macario, Maria Carla / Rubin, Michela / Dal Maschio, Marco / Roveri, Antonella / Moro, Enrico

    Cell death & disease

    2024  Volume 15, Issue 4, Page(s) 269

    Abstract: Most of the patients affected by neuronopathic forms of Mucopolysaccharidosis type II (MPS II), a rare lysosomal storage disorder caused by defects in iduronate-2-sulfatase (IDS) activity, exhibit early neurological defects associated with white matter ... ...

    Abstract Most of the patients affected by neuronopathic forms of Mucopolysaccharidosis type II (MPS II), a rare lysosomal storage disorder caused by defects in iduronate-2-sulfatase (IDS) activity, exhibit early neurological defects associated with white matter lesions and progressive behavioural abnormalities. While neuronal degeneration has been largely described in experimental models and human patients, more subtle neuronal pathogenic defects remain still underexplored. In this work, we discovered that the axon guidance receptor Deleted in Colorectal Cancer (Dcc) is significantly dysregulated in the brain of ids mutant zebrafish since embryonic stages. In addition, thanks to the establishment of neuronal-enriched primary cell cultures, we identified defective proteasomal degradation as one of the main pathways underlying Dcc upregulation in ids mutant conditions. Furthermore, ids mutant fish-derived primary neurons displayed higher levels of polyubiquitinated proteins and P62, suggesting a wider defect in protein degradation. Finally, we show that ids mutant larvae display an atypical response to anxiety-inducing stimuli, hence mimicking one of the characteristic features of MPS II patients. Our study provides an additional relevant frame to MPS II pathogenesis, supporting the concept that multiple developmental defects concur with early childhood behavioural abnormalities.
    MeSH term(s) Animals ; Axon Guidance ; Brain/metabolism ; Iduronate Sulfatase/metabolism ; Mucopolysaccharidosis II/metabolism ; Nervous System Diseases/pathology ; Zebrafish/metabolism
    Chemical Substances Iduronate Sulfatase (EC 3.1.6.13) ; dcc protein, zebrafish
    Language English
    Publishing date 2024-04-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-024-06661-2
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  4. Article ; Online: An Optical Illusion Pinpoints an Essential Circuit Node for Global Motion Processing.

    Wu, Yunmin / Dal Maschio, Marco / Kubo, Fumi / Baier, Herwig

    Neuron

    2020  Volume 108, Issue 4, Page(s) 722–734.e5

    Abstract: Direction-selective (DS) neurons compute the direction of motion in a visual scene. Brain-wide imaging in larval zebrafish has revealed hundreds of DS neurons scattered throughout the brain. However, the exact population that causally drives motion- ... ...

    Abstract Direction-selective (DS) neurons compute the direction of motion in a visual scene. Brain-wide imaging in larval zebrafish has revealed hundreds of DS neurons scattered throughout the brain. However, the exact population that causally drives motion-dependent behaviors-e.g., compensatory eye and body movements-remains largely unknown. To identify the behaviorally relevant population of DS neurons, here we employ the motion aftereffect (MAE), which causes the well-known "waterfall illusion." Together with region-specific optogenetic manipulations and cellular-resolution functional imaging, we found that MAE-responsive neurons represent merely a fraction of the entire population of DS cells in larval zebrafish. They are spatially clustered in a nucleus in the ventral lateral pretectal area and are necessary and sufficient to steer the entire cycle of optokinetic eye movements. Thus, our illusion-based behavioral paradigm, combined with optical imaging and optogenetics, identified key circuit elements of global motion processing in the vertebrate brain.
    MeSH term(s) Afterimage/physiology ; Animals ; Animals, Genetically Modified ; Eye Movements/physiology ; Motion Perception/physiology ; Neuroimaging/methods ; Optical Illusions/physiology ; Optogenetics ; Photic Stimulation ; Pretectal Region/physiology ; Zebrafish
    Language English
    Publishing date 2020-09-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2020.08.027
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  5. Article ; Online: Aberrant Patterns of Sensory-Evoked Activity in the Olfactory Bulb of LRRK2 Knockout Mice.

    Maset, Andrea / Albanesi, Marco / di Soccio, Antonio / Canova, Martina / Dal Maschio, Marco / Lodovichi, Claudia

    Cells

    2021  Volume 10, Issue 11

    Abstract: The LRRK2 gene is the major genetic determinant of familiar Parkinson's disease (PD). Leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein involved in several intracellular signaling pathways. A wealth of evidence indicates that LRRK2 is ... ...

    Abstract The LRRK2 gene is the major genetic determinant of familiar Parkinson's disease (PD). Leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein involved in several intracellular signaling pathways. A wealth of evidence indicates that LRRK2 is enriched at the presynaptic compartment where it regulates vesicle trafficking and neurotransmitter release. However, whether the role of LRRK2 affects neuronal networks dynamic at systems level remains unknown. Addressing this question is critical to unravel the impact of LRRK2 on brain function. Here, combining behavioral tests, electrophysiological recordings, and functional imaging, we investigated neuronal network dynamics, in vivo, in the olfactory bulb of mice carrying a null mutation in LRRK2 gene (LRRK2 knockout, LRRK2 KO, mice). We found that LRRK2 KO mice exhibit olfactory behavioral deficits. At the circuit level, the lack of LRRK2 expression results in altered gamma rhythms and odorant-evoked activity with significant impairments, while the spontaneous activity exhibited limited alterations. Overall, our data in the olfactory bulb suggest that the multifaced role of LRRK2 has a strong impact at system level when the network is engaged in active sensory processing.
    MeSH term(s) Action Potentials/physiology ; Animals ; Evoked Potentials/physiology ; Female ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/deficiency ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation/genetics ; Odorants ; Olfactory Bulb/physiology ; Sensation/physiology ; Mice
    Chemical Substances Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (EC 2.7.11.1) ; Lrrk2 protein, mouse (EC 2.7.11.1)
    Language English
    Publishing date 2021-11-17
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10113212
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  6. Article: Male violence disrupts estrogen receptor β signaling in the female hippocampus.

    Agrimi, Jacopo / Bernardele, Lucia / Sbaiti, Naeem / Canato, Marta / Marchionni, Ivan / Oeing, Christian U / Vignoli, Beatrice / Canossa, Marco / Kaludercic, Nina / Lodovichi, Claudia / Dal Maschio, Marco / Paolocci, Nazareno

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Women are the main target of intimate partner violence (IPV), which is escalating worldwide. Mechanisms subtending IPV-related disorders, such as anxiety, depression and PTSD, remain unclear. We employed a mouse model molded on an IPV scenario ( ... ...

    Abstract Women are the main target of intimate partner violence (IPV), which is escalating worldwide. Mechanisms subtending IPV-related disorders, such as anxiety, depression and PTSD, remain unclear. We employed a mouse model molded on an IPV scenario (male
    Language English
    Publishing date 2023-09-23
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.23.559092
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  7. Article ; Online: Whole brain functional recordings at cellular resolution in zebrafish larvae with 3D scanning multiphoton microscopy.

    Bruzzone, Matteo / Chiarello, Enrico / Albanesi, Marco / Miletto Petrazzini, Maria Elena / Megighian, Aram / Lodovichi, Claudia / Dal Maschio, Marco

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 11048

    Abstract: Optical recordings of neuronal activity at cellular resolution represent an invaluable tool to investigate brain mechanisms. Zebrafish larvae is one of the few model organisms where, using fluorescence-based reporters of the cell activity, it is possible ...

    Abstract Optical recordings of neuronal activity at cellular resolution represent an invaluable tool to investigate brain mechanisms. Zebrafish larvae is one of the few model organisms where, using fluorescence-based reporters of the cell activity, it is possible to optically reconstruct the neuronal dynamics across the whole brain. Typically, leveraging the reduced light scattering, methods like lightsheet, structured illumination, and light-field microscopy use spatially extended excitation profiles to detect in parallel activity signals from multiple cells. Here, we present an alternative design for whole brain imaging based on sequential 3D point-scanning excitation. Our approach relies on a multiphoton microscope integrating an electrically tunable lens. We first apply our approach, adopting the GCaMP6s activity reporter, to detect functional responses from retinal ganglion cells (RGC) arborization fields at different depths within the zebrafish larva midbrain. Then, in larvae expressing a nuclear localized GCaMP6s, we recorded whole brain activity with cellular resolution. Adopting a semi-automatic cell segmentation, this allowed reconstructing the activity from up to 52,000 individual neurons across the brain. In conclusion, this design can easily retrofit existing imaging systems and represents a compact, versatile and reliable tool to investigate neuronal activity across the larva brain at high resolution.
    MeSH term(s) Animals ; Brain/physiology ; Microscopy, Fluorescence, Multiphoton ; Photic Stimulation ; Retinal Ganglion Cells/physiology ; Zebrafish
    Language English
    Publishing date 2021-05-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-90335-y
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  8. Article ; Online: An optogenetic toolbox for unbiased discovery of functionally connected cells in neural circuits.

    Förster, Dominique / Dal Maschio, Marco / Laurell, Eva / Baier, Herwig

    Nature communications

    2017  Volume 8, Issue 1, Page(s) 116

    Abstract: Optical imaging approaches have revolutionized our ability to monitor neural network dynamics, but by themselves are unable to link a neuron's activity to its functional connectivity. We present a versatile genetic toolbox, termed 'Optobow', for all- ... ...

    Abstract Optical imaging approaches have revolutionized our ability to monitor neural network dynamics, but by themselves are unable to link a neuron's activity to its functional connectivity. We present a versatile genetic toolbox, termed 'Optobow', for all-optical discovery of excitatory connections in vivo. By combining the Gal4-UAS system with Cre/lox recombination, we target the optogenetic actuator ChrimsonR and the sensor GCaMP6 to stochastically labeled, nonoverlapping and sparse subsets of neurons. Photostimulation of single cells using two-photon computer-generated holography evokes calcium responses in downstream neurons. Morphological reconstruction of neurite arbors, response latencies and localization of presynaptic markers suggest that some neuron pairs recorded here are directly connected, while others are two or more synapses apart from each other. With this toolbox, we discover wiring principles between specific cell types in the larval zebrafish tectum. Optobow should be useful for identification and manipulation of networks of interconnected neurons, even in dense neural tissues.Mechanisms of neural processing can only be understood by revealing patterns of connectivity among the cellular components of the circuit. Here the authors report a new genetic toolbox, 'Optobow', which enables simultaneous optogenetic activation of single neurons in zebrafish and measuring the activity of downstream neurons in the network.
    Language English
    Publishing date 2017--24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2041-1723
    ISSN (online) 2041-1723
    DOI 10.1038/s41467-017-00160-z
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  9. Article ; Online: Linking Neurons to Network Function and Behavior by Two-Photon Holographic Optogenetics and Volumetric Imaging.

    Dal Maschio, Marco / Donovan, Joseph C / Helmbrecht, Thomas O / Baier, Herwig

    Neuron

    2017  Volume 94, Issue 4, Page(s) 774–789.e5

    Abstract: We introduce a flexible method for high-resolution interrogation of circuit function, which combines simultaneous 3D two-photon stimulation of multiple targeted neurons, volumetric functional imaging, and quantitative behavioral tracking. This integrated ...

    Abstract We introduce a flexible method for high-resolution interrogation of circuit function, which combines simultaneous 3D two-photon stimulation of multiple targeted neurons, volumetric functional imaging, and quantitative behavioral tracking. This integrated approach was applied to dissect how an ensemble of premotor neurons in the larval zebrafish brain drives a basic motor program, the bending of the tail. We developed an iterative photostimulation strategy to identify minimal subsets of channelrhodopsin (ChR2)-expressing neurons that are sufficient to initiate tail movements. At the same time, the induced network activity was recorded by multiplane GCaMP6 imaging across the brain. From this dataset, we computationally identified activity patterns associated with distinct components of the elicited behavior and characterized the contributions of individual neurons. Using photoactivatable GFP (paGFP), we extended our protocol to visualize single functionally identified neurons and reconstruct their morphologies. Together, this toolkit enables linking behavior to circuit activity with unprecedented resolution.
    MeSH term(s) Animals ; Animals, Genetically Modified ; Behavior, Animal/physiology ; Brain/physiology ; Channelrhodopsins ; Green Fluorescent Proteins ; Holography ; Movement/physiology ; Nerve Net/physiology ; Neurons/physiology ; Optogenetics ; Photic Stimulation ; Photons ; Tail ; Zebrafish
    Chemical Substances Channelrhodopsins ; Green Fluorescent Proteins (147336-22-9)
    Language English
    Publishing date 2017-05-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2017.04.034
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  10. Article ; Online: Automated synapse-level reconstruction of neural circuits in the larval zebrafish brain.

    Svara, Fabian / Förster, Dominique / Kubo, Fumi / Januszewski, Michał / Dal Maschio, Marco / Schubert, Philipp J / Kornfeld, Jörgen / Wanner, Adrian A / Laurell, Eva / Denk, Winfried / Baier, Herwig

    Nature methods

    2022  Volume 19, Issue 11, Page(s) 1357–1366

    Abstract: Dense reconstruction of synaptic connectivity requires high-resolution electron microscopy images of entire brains and tools to efficiently trace neuronal wires across the volume. To generate such a resource, we sectioned and imaged a larval zebrafish ... ...

    Abstract Dense reconstruction of synaptic connectivity requires high-resolution electron microscopy images of entire brains and tools to efficiently trace neuronal wires across the volume. To generate such a resource, we sectioned and imaged a larval zebrafish brain by serial block-face electron microscopy at a voxel size of 14 × 14 × 25 nm<sup>3</sup>. We segmented the resulting dataset with the flood-filling network algorithm, automated the detection of chemical synapses and validated the results by comparisons to transmission electron microscopic images and light-microscopic reconstructions. Neurons and their connections are stored in the form of a queryable and expandable digital address book. We reconstructed a network of 208 neurons involved in visual motion processing, most of them located in the pretectum, which had been functionally characterized in the same specimen by two-photon calcium imaging. Moreover, we mapped all 407 presynaptic and postsynaptic partners of two superficial interneurons in the tectum. The resource developed here serves as a foundation for synaptic-resolution circuit analyses in the zebrafish nervous system.
    MeSH term(s) Animals ; Zebrafish ; Larva ; Synapses/ultrastructure ; Brain/ultrastructure ; Microscopy, Electron
    Language English
    Publishing date 2022-10-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2169522-2
    ISSN 1548-7105 ; 1548-7091
    ISSN (online) 1548-7105
    ISSN 1548-7091
    DOI 10.1038/s41592-022-01621-0
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