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  1. Article: Investigating the Effects of Mechanical Stimulation on Retinal Ganglion Cell Spontaneous Spiking Activity.

    Marrese, Marica / Lonardoni, Davide / Boi, Fabio / van Hoorn, Hedde / Maccione, Alessandro / Zordan, Stefano / Iannuzzi, Davide / Berdondini, Luca

    Frontiers in neuroscience

    2019  Volume 13, Page(s) 1023

    Abstract: Mechanical forces are increasingly recognized as major regulators of several physiological processes at both the molecular and cellular level; therefore, a deep understanding of the sensing of these forces and their conversion into electrical signals are ...

    Abstract Mechanical forces are increasingly recognized as major regulators of several physiological processes at both the molecular and cellular level; therefore, a deep understanding of the sensing of these forces and their conversion into electrical signals are essential for studying the mechanosensitive properties of soft biological tissues. To contribute to this field, we present a dual-purpose device able to mechanically stimulate retinal tissue and to record the spiking activity of retinal ganglion cells (RGCs). This new instrument relies on combining ferrule-top micro-indentation, which provides local measurements of viscoelasticity, with high-density multi-electrode array (HD-MEAs) to simultaneously record the spontaneous activity of the retina. In this paper, we introduce this instrument, describe its technical characteristics, and present a proof-of-concept experiment that shows how RGC spiking activity of explanted mice retinas respond to mechanical micro-stimulations of their photoreceptor layer. The data suggest that, under specific conditions of indentation, the retina perceive the mechanical stimulation as modulation of the visual input, besides the longer time-scale of activation, and the increase in spiking activity is not only localized under the indentation probe, but it propagates across the retinal tissue.
    Language English
    Publishing date 2019-09-27
    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.2019.01023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Active High-Density Electrode Arrays: Technology and Applications in Neuronal Cell Cultures.

    Lonardoni, Davide / Amin, Hayder / Zordan, Stefano / Boi, Fabio / Lecomte, Aziliz / Angotzi, Gian Nicola / Berdondini, Luca

    Advances in neurobiology

    2019  Volume 22, Page(s) 253–273

    Abstract: Active high-density electrode arrays realized with complementary metal-oxide-semiconductor (CMOS) technology provide electrophysiological recordings from several thousands of closely spaced microelectrodes. This has drastically advanced the ... ...

    Abstract Active high-density electrode arrays realized with complementary metal-oxide-semiconductor (CMOS) technology provide electrophysiological recordings from several thousands of closely spaced microelectrodes. This has drastically advanced the spatiotemporal recording resolution of conventional multielectrode arrays (MEAs). Thus, today's electrophysiology in neuronal cultures can exploit label-free electrical readouts from a large number of single neurons within the same network. This provides advanced capabilities to investigate the properties of self-assembling neuronal networks, to advance studies on neurotoxicity and neurodevelopmental alterations associated with human brain diseases, and to develop cell culture models for testing drug- or cell-based strategies for therapies.Here, after introducing the reader to this neurotechnology, we summarize the results of different recent studies demonstrating the potential of active high-density electrode arrays for experimental applications. We also discuss ongoing and possible future research directions that might allow for moving these platforms forward for screening applications.
    MeSH term(s) Action Potentials ; Cell Culture Techniques ; Electrophysiology/instrumentation ; Electrophysiology/methods ; Humans ; Microelectrodes ; Neurons/cytology ; Neurons/pathology ; Neurons/physiology
    Language English
    Publishing date 2019-05-09
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2190-5215
    ISSN 2190-5215
    DOI 10.1007/978-3-030-11135-9_11
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Doxycycline rescues recognition memory and circadian motor rhythmicity but does not prevent terminal disease in fatal familial insomnia mice.

    Lavigna, Giada / Masone, Antonio / Bouybayoune, Ihssane / Bertani, Ilaria / Lucchetti, Jacopo / Gobbi, Marco / Porcu, Luca / Zordan, Stefano / Rigamonti, Mara / Imeri, Luca / Restelli, Elena / Chiesa, Roberto

    Neurobiology of disease

    2021  Volume 158, Page(s) 105455

    Abstract: Fatal familial insomnia (FFI) is a dominantly inherited prion disease linked to the D178N mutation in the gene encoding the prion protein (PrP). Symptoms, including insomnia, memory loss and motor abnormalities, appear around 50 years of age, leading to ... ...

    Abstract Fatal familial insomnia (FFI) is a dominantly inherited prion disease linked to the D178N mutation in the gene encoding the prion protein (PrP). Symptoms, including insomnia, memory loss and motor abnormalities, appear around 50 years of age, leading to death within two years. No treatment is available. A ten-year clinical trial of doxycycline (doxy) is under way in healthy individuals at risk of FFI to test whether presymptomatic doxy prevents or delays the onset of disease. To assess the drug's effect in a tractable disease model, we used Tg(FFI-26) mice, which accumulate aggregated and protease-resistant PrP in their brains and develop a fatal neurological illness highly reminiscent of FFI. Mice were treated daily with 10 mg/kg doxy starting from a presymptomatic stage for twenty weeks. Doxy rescued memory deficits and restored circadian motor rhythmicity in Tg(FFI-26) mice. However, it did not prevent the onset and progression of motor dysfunction, clinical signs and progression to terminal disease. Doxy did not change the amount of aggregated and protease-resistant PrP, but reduced microglial activation in the hippocampus. Presymptomatic doxy treatment rescues cognitive impairment and the motor correlates of sleep dysfunction in Tg(FFI-26) mice but does not prevent fatal disease.
    MeSH term(s) Animals ; Brain/pathology ; Circadian Rhythm/drug effects ; Disease Progression ; Doxycycline/pharmacology ; Doxycycline/therapeutic use ; Insomnia, Fatal Familial/drug therapy ; Insomnia, Fatal Familial/genetics ; Insomnia, Fatal Familial/pathology ; Memory/drug effects ; Mice ; Mice, Inbred C57BL ; Motor Activity/drug effects ; Psychomotor Performance/drug effects ; Recognition, Psychology/drug effects
    Chemical Substances Doxycycline (N12000U13O)
    Language English
    Publishing date 2021-08-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1211786-9
    ISSN 1095-953X ; 0969-9961
    ISSN (online) 1095-953X
    ISSN 0969-9961
    DOI 10.1016/j.nbd.2021.105455
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4444: 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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  4. Article: Electrical Responses and Spontaneous Activity of Human iPS-Derived Neuronal Networks Characterized for 3-month Culture with 4096-Electrode Arrays.

    Amin, Hayder / Maccione, Alessandro / Marinaro, Federica / Zordan, Stefano / Nieus, Thierry / Berdondini, Luca

    Frontiers in neuroscience

    2016  Volume 10, Page(s) 121

    Abstract: The recent availability of human induced pluripotent stem cells (hiPSCs) holds great promise as a novel source of human-derived neurons for cell and tissue therapies as well as for in vitro drug screenings that might replace the use of animal models. ... ...

    Abstract The recent availability of human induced pluripotent stem cells (hiPSCs) holds great promise as a novel source of human-derived neurons for cell and tissue therapies as well as for in vitro drug screenings that might replace the use of animal models. However, there is still a considerable lack of knowledge on the functional properties of hiPSC-derived neuronal networks, thus limiting their application. Here, upon optimization of cell culture protocols, we demonstrate that both spontaneous and evoked electrical spiking activities of these networks can be characterized on-chip by taking advantage of the resolution provided by CMOS multielectrode arrays (CMOS-MEAs). These devices feature a large and closely-spaced array of 4096 simultaneously recording electrodes and multi-site on-chip electrical stimulation. Our results show that networks of human-derived neurons can respond to electrical stimulation with a physiological repertoire of spike waveforms after 3 months of cell culture, a period of time during which the network undergoes the expression of developing patterns of spontaneous spiking activity. To achieve this, we have investigated the impact on the network formation and on the emerging network-wide functional properties induced by different biochemical substrates, i.e., poly-dl-ornithine (PDLO), poly-l-ornithine (PLO), and polyethylenimine (PEI), that were used as adhesion promoters for the cell culture. Interestingly, we found that neuronal networks grown on PDLO coated substrates show significantly higher spontaneous firing activity, reliable responses to low-frequency electrical stimuli, and an appropriate level of PSD-95 that may denote a physiological neuronal maturation profile and synapse stabilization. However, our results also suggest that even 3-month culture might not be sufficient for human-derived neuronal network maturation. Taken together, our results highlight the tight relationship existing between substrate coatings and emerging network properties, i.e., spontaneous activity, responsiveness, synapse formation and maturation. Additionally, our results provide a baseline on the functional properties expressed over 3 months of network development for a commercially available line of hiPSC-derived neurons. This is a first step toward the development of functional pre-clinical assays to test pharmaceutical compounds on human-derived neuronal networks with CMOS-MEAs.
    Language English
    Publishing date 2016-03-30
    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.2016.00121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A programmable closed-loop recording and stimulating wireless system for behaving small laboratory animals.

    Angotzi, Gian Nicola / Boi, Fabio / Zordan, Stefano / Bonfanti, Andrea / Vato, Alessandro

    Scientific reports

    2014  Volume 4, Page(s) 5963

    Abstract: A portable 16-channels microcontroller-based wireless system for a bi-directional interaction with the central nervous system is presented in this work. The device is designed to be used with freely behaving small laboratory animals and allows recording ... ...

    Abstract A portable 16-channels microcontroller-based wireless system for a bi-directional interaction with the central nervous system is presented in this work. The device is designed to be used with freely behaving small laboratory animals and allows recording of spontaneous and evoked neural activity wirelessly transmitted and stored on a personal computer. Biphasic current stimuli with programmable duration, frequency and amplitude may be triggered in real-time on the basis of the recorded neural activity as well as by the animal behavior within a specifically designed experimental setup. An intuitive graphical user interface was developed to configure and to monitor the whole system. The system was successfully tested through bench tests and in vivo measurements on behaving rats chronically implanted with multi-channels microwire arrays.
    MeSH term(s) Action Potentials/physiology ; Animals ; Behavior, Animal/physiology ; Brain-Computer Interfaces ; Electric Stimulation ; Electrodes, Implanted ; Equipment Design ; Male ; Rats ; Rats, Long-Evans ; Remote Sensing Technology/instrumentation ; Signal Processing, Computer-Assisted/instrumentation ; Somatosensory Cortex/physiology ; Somatosensory Cortex/surgery ; Stereotaxic Techniques ; Wireless Technology/instrumentation
    Language English
    Publishing date 2014-08-06
    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/srep05963
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Microelectronics, bioinformatics and neurocomputation for massive neuronal recordings in brain circuits with large scale multielectrode array probes.

    Maccione, Alessandro / Gandolfo, Mauro / Zordan, Stefano / Amin, Hayder / Di Marco, Stefano / Nieus, Thierry / Angotzi, Gian Nicola / Berdondini, Luca

    Brain research bulletin

    2015  Volume 119, Issue Pt B, Page(s) 118–126

    Abstract: Deciphering neural network function in health and disease requires recording from many active neurons simultaneously. Developing approaches to increase their numbers is a major neurotechnological challenge. Parallel to recent advances in optical Ca(2+) ... ...

    Abstract Deciphering neural network function in health and disease requires recording from many active neurons simultaneously. Developing approaches to increase their numbers is a major neurotechnological challenge. Parallel to recent advances in optical Ca(2+) imaging, an emerging approach consists in adopting complementary-metal-oxide-semiconductor (CMOS) technology to realize MultiElectrode Array (MEA) devices. By implementing signal conditioning and multiplexing circuits, these devices allow nowadays to record from several thousands of single neurons at sub-millisecond temporal resolution. At the same time, these recordings generate very large data streams which become challenging to analyze. Here, at first we shortly review the major approaches developed for data management and analysis for conventional, low-resolution MEAs. We highlight how conventional computational tools cannot be easily up-scaled to very large electrode array recordings, and custom bioinformatics tools are an emerging need in this field. We then introduce a novel approach adapted for the acquisition, compression and analysis of extracellular signals acquired simultaneously from 4096 electrodes with CMOS MEAs. Finally, as a case study, we describe how this novel large scale recording platform was used to record and analyze extracellular spikes from the ganglion cell layer in the wholemount retina at pan-retinal scale following patterned light stimulation.
    MeSH term(s) Action Potentials/physiology ; Animals ; Brain/physiology ; Computational Biology/instrumentation ; Computational Biology/methods ; Computational Biology/trends ; Electric Stimulation/methods ; Microelectrodes/trends ; Neuroimaging/instrumentation ; Neuroimaging/methods ; Neuroimaging/trends ; Neurons/physiology ; Semiconductors
    Language English
    Publishing date 2015-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 197620-5
    ISSN 1873-2747 ; 0361-9230
    ISSN (online) 1873-2747
    ISSN 0361-9230
    DOI 10.1016/j.brainresbull.2015.07.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1243: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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