@article{MTMT:34341943, title = {Behavioral, neural and ultrastructural alterations in a graded-dose 6-OHDA mouse model of early-stage Parkinson's disease}, url = {https://m2.mtmt.hu/api/publication/34341943}, author = {Slézia, Andrea and Hegedüs, Panna and Rusina, Evgeniia and Lengyel, Katalin and Solari, Nicola and Kaszás, Attila and Balázsfi, Diána and Botzanowski, Boris and Acerbo, Emma and Missey, Florian and Williamson, Adam and Hangya, Balázs}, doi = {10.1038/s41598-023-46576-0}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {13}, unique-id = {34341943}, issn = {2045-2322}, abstract = {Studying animal models furthers our understanding of Parkinson’s disease (PD) pathophysiology by providing tools to investigate detailed molecular, cellular and circuit functions. Different versions of the neurotoxin-based 6-hydroxydopamine (6-OHDA) model of PD have been widely used in rats. However, these models typically assess the result of extensive and definitive dopaminergic lesions that reflect a late stage of PD, leading to a paucity of studies and a consequential gap of knowledge regarding initial stages, in which early interventions would be possible. Additionally, the better availability of genetic tools increasingly shifts the focus of research from rats to mice, but few mouse PD models are available yet. To address these, we characterize here the behavioral, neuronal and ultrastructural features of a graded-dose unilateral, single-injection, striatal 6-OHDA model in mice, focusing on early-stage changes within the first two weeks of lesion induction. We observed early onset, dose-dependent impairments of overall locomotion without substantial deterioration of motor coordination. In accordance, histological evaluation demonstrated a partial, dose-dependent loss of dopaminergic neurons of substantia nigra pars compacta (SNc). Furthermore, electron microscopic analysis revealed degenerative ultrastructural changes in SNc dopaminergic neurons. Our results show that mild ultrastructural and cellular degradation of dopaminergic neurons of the SNc can lead to certain motor deficits shortly after unilateral striatal lesions, suggesting that a unilateral dose-dependent intrastriatal 6-OHDA lesion protocol can serve as a successful model of the early stages of Parkinson’s disease in mice.}, year = {2023}, eissn = {2045-2322}, orcid-numbers = {Slézia, Andrea/0000-0002-4528-3169; Hegedüs, Panna/0000-0002-9984-5729} } @article{MTMT:33729235, title = {Transparent neural interfaces: challenges and solutions of microengineered multimodal implants designed to measure intact neuronal populations using high-resolution electrophysiology and microscopy simultaneously}, url = {https://m2.mtmt.hu/api/publication/33729235}, author = {Fekete, Zoltán and Zátonyi, Anita and Kaszás, Attila and Madarász, Miklós and Slézia, Andrea}, doi = {10.1038/s41378-023-00519-x}, journal-iso = {MICROSYST NANOENG}, journal = {MICROSYSTEMS & NANOENGINEERING}, volume = {9}, unique-id = {33729235}, issn = {2055-7434}, year = {2023}, eissn = {2055-7434}, orcid-numbers = {Fekete, Zoltán/0000-0002-6718-4022; Madarász, Miklós/0000-0001-7057-303X; Slézia, Andrea/0000-0002-4528-3169} } @article{MTMT:32030456, title = {Two-photon GCaMP6f imaging of infrared neural stimulation evoked calcium signals in mouse cortical neurons in vivo}, url = {https://m2.mtmt.hu/api/publication/32030456}, author = {Kaszas, A. and Szalay, Gergely and Slézia, Andrea and Bojdán, Alexandra and Vanzetta, I. and Hangya, Balázs and Rózsa J., Balázs and O’Connor, R. and Moreau, D.}, doi = {10.1038/s41598-021-89163-x}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {11}, unique-id = {32030456}, issn = {2045-2322}, year = {2021}, eissn = {2045-2322}, orcid-numbers = {Slézia, Andrea/0000-0002-4528-3169} } @article{MTMT:31310201, title = {In Vivo Characterization of Neurophysiological Diversity in the Lateral Supramammillary Nucleus during Hippocampal Sharp-wave Ripples of Adult Rats}, url = {https://m2.mtmt.hu/api/publication/31310201}, author = {Vicente, A.F. and Slézia, Andrea and Ghestem, A. and Bernard, C. and Quilichini, P.P.}, doi = {10.1016/j.neuroscience.2020.03.034}, journal-iso = {NEUROSCIENCE}, journal = {NEUROSCIENCE}, volume = {435}, unique-id = {31310201}, issn = {0306-4522}, keywords = {Adult; Male; hippocampus; hippocampus; ARTICLE; nonhuman; animal experiment; oscillation; memory consolidation; Slow oscillation; Theta; nerve cell; cell activation; in vivo study; firing; sharp-wave ripple; rat; lateral supramammillary nucleus}, year = {2020}, eissn = {1873-7544}, pages = {95-111}, orcid-numbers = {Slézia, Andrea/0000-0002-4528-3169} } @article{MTMT:30792625, title = {Electrophoretic Delivery of gamma-aminobutyric Acid (GABA) into Epileptic Focus Prevents Seizures in Mice}, url = {https://m2.mtmt.hu/api/publication/30792625}, author = {Slézia, Andrea and Proctor, Christopher M. and Kaszas, Attila and Malliaras, George G. and Williamson, Adam (John)}, doi = {10.3791/59268}, journal-iso = {JOVE-J VIS EXP}, journal = {JOVE-JOURNAL OF VISUALIZED EXPERIMENTS}, unique-id = {30792625}, issn = {1940-087X}, abstract = {Epilepsy is a group of neurological disorders which affects millions of people worldwide. Although treatment with medication is helpful in 70% of the cases, serious side effects affect the quality of life of patients. Moreover, a high percentage of epileptic patients are drug resistant; in their case, neurosurgery or neurostimulation are necessary. Therefore, the major goal of epilepsy research is to discover new therapies which are either capable of curing epilepsy without side effects or preventing recurrent seizures in drug-resistant patients. Neuroengineering provides new approaches by using novel strategies and technologies to find better solutions to cure epileptic patients at risk.As a demonstration of a novel experimental protocol in an acute mouse model of epilepsy, a direct in situ electrophoretic drug delivery system is used. Namely, a neural probe incorporating a microfluidic ion pump (mu FIP) for on-demand drug delivery and simultaneous recording of local neural activity is implanted and demonstrated to be capable of controlling 4-aminopyridine-induced (4AP-induced) seizure-like event (SLE) activity. The gamma-aminobutyric acid (GABA) concentration is kept in the physiological range by the precise control of GABA delivery to reach an antiepileptic effect in the seizure focus but not to cause overinhibition-induced rebound bursts. The method allows both the detection of pathological activity and intervention to stop seizures by delivering inhibitory neurotransmitters directly to the epileptic focus with precise spatiotemporal control.As a result of the developments to the experimental method, SLEs can be induced in a highly localized manner that allows seizure control by the precisely tuned GABA delivery at the seizure onset.}, keywords = {hippocampus; EPILEPSY; 4-AMINOPYRIDINE; MOUSE; GABA; ELECTROPHORESIS; seizure; Neuroscience; silicon probe; Issue 147; microfluidic ion pump; mu FIP; epileptic focus; 4AP}, year = {2019}, eissn = {1940-087X}, orcid-numbers = {Slézia, Andrea/0000-0002-4528-3169} } @article{MTMT:30436345, title = {An Electrocorticography Device with an Integrated Microfluidic Ion Pump for Simultaneous Neural Recording and Electrophoretic Drug Delivery In Vivo}, url = {https://m2.mtmt.hu/api/publication/30436345}, author = {Proctor, Christopher M. and Uguz, Ilke and Slézia, Andrea and Curto, Vincenzo and Inal, Sahika and Williamson, Adam (John) and Malliaras, George G.}, doi = {10.1002/adbi.201800270}, journal-iso = {ADV BIOSYST}, journal = {ADVANCED BIOSYSTEMS}, volume = {3}, unique-id = {30436345}, abstract = {The challenge of treating neurological disorders has motivated the development of implantable devices that can deliver treatment when and where it is needed. This study presents a novel brain implant capable of electrophoretically delivering drugs and recording local neural activity on the surface of the brain. The drug delivery is made possible by the integration of a microfluidic ion pump (mu FIP) into a conformable electrocorticography (ECoG) device with recording cites embedded next to the drug delivery outlets. The mu FIP ECoG device can deliver a high capacity of several biologically important cationic species on demand. The therapeutic potential of the device is demonstrated by using it to deliver neurotransmitters in a rodent model while simultaneously recording local neural activity. These developments represent a significant step forward for cortical drug-delivery systems.}, keywords = {electrocorticography; Drug delivery; Bioelectronics; electrophoretic; neuroengineering}, year = {2019}, eissn = {2366-7478}, orcid-numbers = {Proctor, Christopher M./0000-0002-2066-1354; Slézia, Andrea/0000-0002-4528-3169; Williamson, Adam (John)/0000-0002-5632-0084; Malliaras, George G./0000-0002-4582-8501} } @misc{MTMT:32561425, title = {NeuroRoots, a bio-inspired, seamless Brain Machine Interface device for long-term recording}, url = {https://m2.mtmt.hu/api/publication/32561425}, author = {Marc, D. Ferro and Christopher, M. Proctor and Alexander, Gonzalez and Eric, Zhao and Slézia, Andrea and Jolien, Pas and Gerwin, Dijk and Mary, J. Donahue and Adam, Williamson and Georges, G. Malliaras and Lisa, Giocomo and Nicholas, A. Melosh}, doi = {10.1101/460949}, unique-id = {32561425}, year = {2018}, orcid-numbers = {Slézia, Andrea/0000-0002-4528-3169} } @article{MTMT:30580269, title = {A bilayered PVA/PLGA-bioresorbable shuttle to improve the implantation of flexible neural probes}, url = {https://m2.mtmt.hu/api/publication/30580269}, author = {Pas, Jolien and Rutz, Alexandra L. and Quilichini, Pascale P. and Slézia, Andrea and Ghestem, Antoine and Kaszas, Attila and Donahue, Mary J. and Curto, Vincenzo F. and O'Connor, Rodney P. and Bernard, Christophe and Williamson, Adam and Malliaras, George G.}, doi = {10.1088/1741-2552/aadc1d}, journal-iso = {J NEURAL ENG}, journal = {JOURNAL OF NEURAL ENGINEERING}, volume = {15}, unique-id = {30580269}, issn = {1741-2560}, abstract = {Objective. Neural electrophysiology is often conducted with traditional, rigid depth probes. The mechanical mismatch between these probes and soft brain tissue is unfavorable for tissue interfacing. Making probes compliant can improve biocompatibility, but as a consequence, they become more difficult to insert into the brain. Therefore, new methods for inserting compliant neural probes must be developed. Approach. Here, we present a new bioresorbable shuttle based on the hydrolytically degradable poly(vinyl alcohol) (PVA) and poly(lactic-coglycolic acid) (PLGA). We show how to fabricate the PVA/PLGA shuttles on flexible and thin parylene probes. The method consists of PDMS molding used to fabricate a PVA shuttle aligned with the probe and to also impart a sharp tip necessary for piercing brain tissue. The PVA shuttle is then dip-coated with PLGA to create a bi-layered shuttle. Main results. While single layered PVA shuttles are able to penetrate agarose brain models, only limited depths were achieved and repositioning was not possible due to the fast degradation. We demonstrate that a bilayered approach incorporating a slower dissolving PLGA layer prolongs degradation and enables facile insertion for at least several millimeters depth. Impedances of electrodes before and after shuttle preparation were characterized and showed that careful deposition of PLGA is required to maintain low impedance. Facilitated by the shuttles. compliant parylene probes were also successfully implanted into anaesthetized mice and enabled the recording of high quality local field potentials. Significance. This work thereby presents a solution towards addressing a key challenge of implanting compliant neural probes using a two polymer system. PVA and PLGA are polymers with properties ideal for translation: commercially available, biocompatible with FDA-approved uses and bioresorbable. By presenting new ways to implant compliant neural probes, we can begin to fully evaluate their chronic biocompatibility and performance compared to traditional, rigid electronics.}, keywords = {Electrophysiology; Bioelectronics; neural depth probes; poly vinyl alcohol (PVA); poly(lactic-co-glycolic acid) (PLGA)}, year = {2018}, eissn = {1741-2552}, orcid-numbers = {Slézia, Andrea/0000-0002-4528-3169} } @article{MTMT:30484866, title = {Electrophoretic drug delivery for seizure control}, url = {https://m2.mtmt.hu/api/publication/30484866}, author = {Proctor, Christopher M. and Slézia, Andrea and Kaszas, Attila and Ghestem, Antoine and del Agua, Isabel and Pappa, Anna-Maria and Bernard, Christophe and Williamson, Adam and Malliaras, George G.}, doi = {10.1126/sciadv.aau1291}, journal-iso = {SCI ADV}, journal = {SCIENCE ADVANCES}, volume = {4}, unique-id = {30484866}, issn = {2375-2548}, abstract = {The persistence of intractable neurological disorders necessitates novel therapeutic solutions. We demonstrate the utility of direct in situ electrophoretic drug delivery to treat neurological disorders. We present a neural probe incorporating a microfluidic ion pump (mu FIP) for on-demand drug delivery and electrodes for recording local neural activity. The mu FIP works by electrophoretically pumping ions across an ion exchange membrane and thereby delivers only the drug of interest and not the solvent. This "dry" delivery enables precise drug release into the brain region with negligible local pressure increase. The therapeutic potential of the mu FIP probe is tested in a rodent model of epilepsy. The mu FIP probe can detect pathological activity and then intervene to stop seizures by delivering inhibitory neurotransmitters directly to the seizure source. We anticipate that further tailored engineering of the mu FIP platform will enable additional applications in neural interfacing and the treatment of neurological disorders.}, year = {2018}, eissn = {2375-2548}, orcid-numbers = {Slézia, Andrea/0000-0002-4528-3169; del Agua, Isabel/0000-0002-8751-5503} } @article{MTMT:30382220, title = {Multimodal Characterization of Neural Networks using Highly Transparent Electrode Arrays}, url = {https://m2.mtmt.hu/api/publication/30382220}, author = {Donahue, Mary J. and Kaszas, Attila and Turi, Gergely F. and Rózsa J., Balázs and Slézia, Andrea and Vanzetta, Ivo and Katona, Gergely and Bernard, Christophe and Malliaras, George G. and Williamson, Adam (John)}, doi = {10.1523/ENEURO.0187-18.2018}, journal-iso = {ENEURO}, journal = {ENEURO}, volume = {5}, unique-id = {30382220}, abstract = {Transparent and flexible materials are attractive for a wide range of emerging bioelectronic applications. These include neural interfacing devices for both recording and stimulation, where low electrochemical electrode impedance is valuable. Here the conducting polymer poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) is utilized to fabricate electrodes that are small enough to allow unencumbered optical access for imaging a large cell population with two-photon (2P) microscopy, yet provide low impedance for simultaneous high quality recordings of neural activity in vivo. To demonstrate this, pathophysiological activity was induced in the mouse cortex using 4-aminopyridine (4AP) and the resulting electrical activity was detected with the PEDOT:PSS-based probe while imaging calcium activity directly below the probe area. The induced calcium activity of the neuronal network as measured by the fluorescence change in the cells correlated well with the electrophysiological recordings from the cortical grid of PEDOT:PSS microelectrodes. Our approach provides a valuable vehicle for complementing classical high temporal resolution electrophysiological analysis with optical imaging.}, year = {2018}, eissn = {2373-2822}, orcid-numbers = {Slézia, Andrea/0000-0002-4528-3169; Katona, Gergely/0000-0002-4173-0355} }