@article{MTMT:35087576, title = {Silicon Optrode with a Micromirror‐Tip Providing Tunable Beam Profile During Infrared Neuromodulation of the Rat Neocortex}, url = {https://m2.mtmt.hu/api/publication/35087576}, author = {Horváth, Ágoston Csaba and Mórocz, Ákos and Csomai, Borbála and Szabó, Ágnes and Balogh-Lantos, Zsófia and Fürjes, Péter and Tóth, Estilla Zsófia and Fiáth, Richárd and Fekete, Zoltán}, doi = {10.1002/admt.202400044}, journal-iso = {ADV MATER TECHNOL-US}, journal = {ADVANCED MATERIALS TECHNOLOGIES}, volume = {in press}, unique-id = {35087576}, issn = {2365-709X}, abstract = {Infrared (IR) neuromodulation holds an increasing potential in brain research, which is fueled by novel neuroengineering approaches facilitating the exploration of the biophysical mechanism in the microscale. The group lays down the fundamentals of spatially controlled optical manipulation of inherently temperature‐sensitive neuronal populations. The concept and in vivo validation of a multifunctional, optical stimulation microdevice is presented, which expands the capabilities of conventional optrodes by coupling IR light through a monolithically integrated parabolic micromirror. Heat distribution in the irradiated volume is experimentally analyzed, and the performance of the integrated electrophysiological recording components of the device is tested in the neocortex of anesthetized rodents. Evoked single‐cell responses upon IR irradiation through the novel microtool are evaluated in multiple trials. The safe operation of the implanted device is also presented using immunohistological methods. The results confirm that shift in temperature distribution in the vicinity of the optrode tip can be controlled by the integrated photonic components, and in parallel with the optical stimulation, the device is suitable to interrogate the evoked electrophysiological activity at the single neuron level. The customizable and scalable optrode system provides a new pathway to tailor the location of the heat maximum during infrared neural stimulation.}, year = {2024}, eissn = {2365-709X}, orcid-numbers = {Horváth, Ágoston Csaba/0000-0003-2114-9309; Fürjes, Péter/0000-0002-8022-4367; Fiáth, Richárd/0000-0001-8732-2691; Fekete, Zoltán/0000-0002-6718-4022} } @mastersthesis{MTMT:35057347, title = {Different Aspects of Electrophysiological and Quantitative Electron Microscopic Investigations in the Rat and the Human Neocortex}, url = {https://m2.mtmt.hu/api/publication/35057347}, author = {Tóth, Estilla Zsófia}, doi = {10.14753/SE.2024.2926}, unique-id = {35057347}, year = {2024} } @article{MTMT:34205650, title = {Effective Synthesis, Development and Application of a Highly Fluorescent Cyanine Dye for Antibody Conjugation and Microscopy Imaging}, url = {https://m2.mtmt.hu/api/publication/34205650}, author = {Szepesi Kovács, Dénes and Kontra, Bence and Chiovini, Balázs and Müller, Dalma and Tóth, Estilla Zsófia and Ábrányi-Balogh, Péter and Wittner, Lucia and Várady, György and Turczel, Gábor and Farkas, Ödön and Owen, Michael Christopher and Katona, Gergely and Győrffy, Balázs and Keserű, György Miklós and Mucsi, Zoltán and Rózsa J., Balázs and Kovács, Ervin}, doi = {10.1039/D3OB01471A}, journal-iso = {ORG BIOMOL CHEM}, journal = {ORGANIC & BIOMOLECULAR CHEMISTRY}, volume = {21}, unique-id = {34205650}, issn = {1477-0520}, abstract = {An asymmetric cyanine-type fluorescent dye was designed and synthesized via a versatile, multi-step process, aiming to conjugate with an Her2+ receptor specific antibody by an azide-alkyne click reaction. The aromaticity and the excitation and relaxation energetics of the fluorophore were characterized by computational methods. The synthesized dye exhibited excellent fluorescence properties for confocal microscopy, offering efficient applicability in in vitro imaging due to its merits such as a high molar absorption coefficient (36 816 M-1 cm-1), excellent brightness, optimal wavelength (627 nm), larger Stokes shift (26 nm) and appropriate photostability compared to cyanines. The conjugated cyanine-trastuzumab was constructed via an effective, metal-free, strain-promoted azide-alkyne click reaction leading to a regulated number of dyes being conjugated. This novel cyanine-labelled antibody was successfully applied for in vitro confocal imaging and flow cytometry of Her2+ tumor cells. An azido cyanine dye was synthesized and characterized by computational and experimental techniques and applied in tumor cell imaging.}, keywords = {RECEPTOR; REAGENTS; FUTURE}, year = {2023}, eissn = {1477-0539}, pages = {8829-8836}, orcid-numbers = {Kontra, Bence/0000-0001-8293-3637; Wittner, Lucia/0000-0001-6800-0953; Várady, György/0000-0003-2012-9680; Farkas, Ödön/0000-0002-4217-0150; Katona, Gergely/0000-0002-4173-0355; Győrffy, Balázs/0000-0002-5772-3766; Mucsi, Zoltán/0000-0003-3224-8847; Rózsa J., Balázs/0000-0003-1427-7003; Kovács, Ervin/0000-0002-3939-6925} } @article{MTMT:34093583, title = {Synaptic alterations and neuronal firing in human epileptic neocortical excitatory networks}, url = {https://m2.mtmt.hu/api/publication/34093583}, author = {Bod, Réka and Tóth, Kinga and ESSAM Fawzy Ahmed Aly, Nour and Tóth, Estilla Zsófia and Erőss, Loránd and Entz, László and Bagó, Attila György and Fabó, Dániel and Ulbert, István and Wittner, Lucia}, doi = {10.3389/fnsyn.2023.1233569}, journal-iso = {FRONT SYNAPTIC NEURO}, journal = {FRONTIERS IN SYNAPTIC NEUROSCIENCE}, volume = {15}, unique-id = {34093583}, issn = {1663-3563}, abstract = {Epilepsy is a prevalent neurological condition, with underlying neuronal mechanisms involving hyperexcitability and hypersynchrony. Imbalance between excitatory and inhibitory circuits, as well as histological reorganization are relatively well-documented in animal models or even in the human hippocampus, but less is known about human neocortical epileptic activity. Our knowledge about changes in the excitatory signaling is especially scarce, compared to that about the inhibitory cell population. This study investigated the firing properties of single neurons in the human neocortex in vitro , during pharmacological blockade of glutamate receptors, and additionally evaluated anatomical changes in the excitatory circuit in tissue samples from epileptic and non-epileptic patients. Both epileptic and non-epileptic tissues exhibited spontaneous population activity (SPA), NMDA receptor antagonization reduced SPA recurrence only in epileptic tissue, whereas further blockade of AMPA/kainate receptors reversibly abolished SPA emergence regardless of epilepsy. Firing rates did not significantly change in excitatory principal cells and inhibitory interneurons during pharmacological experiments. Granular layer (L4) neurons showed an increased firing rate in epileptic compared to non-epileptic tissue. The burstiness of neurons remained unchanged, except for that of inhibitory cells in epileptic recordings, which decreased during blockade of glutamate receptors. Crosscorrelograms computed from single neuron discharge revealed both mono- and polysynaptic connections, particularly involving intrinsically bursting principal cells. Histological investigations found similar densities of SMI-32-immunopositive long-range projecting pyramidal cells in both groups, and shorter excitatory synaptic active zones with a higher proportion of perforated synapses in the epileptic group. These findings provide insights into epileptic modifications from the perspective of the excitatory system and highlight discrete alterations in firing patterns and synaptic structure. Our data suggest that NMDA-dependent glutamatergic signaling, as well as the excitatory synaptic machinery are perturbed in epilepsy, which might contribute to epileptic activity in the human neocortex.}, year = {2023}, eissn = {1663-3563}, orcid-numbers = {Bod, Réka/0000-0001-9744-9282; Tóth, Kinga/0000-0002-8751-8499; Erőss, Loránd/0000-0002-5796-5546; Fabó, Dániel/0000-0001-5141-5351; Ulbert, István/0000-0001-9941-9159; Wittner, Lucia/0000-0001-6800-0953} } @article{MTMT:34015800, title = {Synthesis and Application of Two-Photon Active Fluorescent Rhodol Dyes for Antibody Conjugation and In Vitro Cell Imaging}, url = {https://m2.mtmt.hu/api/publication/34015800}, author = {Szepesi Kovács, Dénes and Chiovini, Balázs and Müller, Dalma and Tóth, Estilla Zsófia and Fülöp, Anna and Ábrányi-Balogh, Péter and Wittner, Lucia and Várady, György and Farkas, Ödön and Turczel, Gábor and Katona, Gergely and Győrffy, Balázs and Keserű, György Miklós and Mucsi, Zoltán and Rózsa J., Balázs and Kovács, Ervin}, doi = {10.1021/acsomega.3c01796}, journal-iso = {ACS OMEGA}, journal = {ACS OMEGA}, volume = {8}, unique-id = {34015800}, issn = {2470-1343}, year = {2023}, eissn = {2470-1343}, pages = {22836-22843}, orcid-numbers = {Wittner, Lucia/0000-0001-6800-0953; Várady, György/0000-0003-2012-9680; Farkas, Ödön/0000-0002-4217-0150; Katona, Gergely/0000-0002-4173-0355; Győrffy, Balázs/0000-0002-5772-3766; Mucsi, Zoltán/0000-0003-3224-8847; Rózsa J., Balázs/0000-0003-1427-7003; Kovács, Ervin/0000-0002-3939-6925} } @article{MTMT:32785453, title = {Bursting of excitatory cells is linked to interictal epileptic discharge generation in humans.}, url = {https://m2.mtmt.hu/api/publication/32785453}, author = {Hofer, Katharina and Kandrács, Ágnes and Tóth, Kinga and Hajnal, Boglárka Zsófia and Bokodi, Virág and Tóth, Estilla Zsófia and Erőss, Loránd and Entz, László and Bagó, Attila György and Fabó, Dániel and Ulbert, István and Wittner, Lucia}, doi = {10.1038/s41598-022-10319-4}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {12}, unique-id = {32785453}, issn = {2045-2322}, abstract = {Knowledge about the activity of single neurons is essential in understanding the mechanisms of synchrony generation, and particularly interesting if related to pathological conditions. The generation of interictal spikes-the hypersynchronous events between seizures-is linked to hyperexcitability and to bursting behaviour of neurons in animal models. To explore its cellular mechanisms in humans we investigated the activity of clustered single neurons in a human in vitro model generating both physiological and epileptiform synchronous events. We show that non-epileptic synchronous events resulted from the finely balanced firing of excitatory and inhibitory cells, which was shifted towards an enhanced excitability in epileptic tissue. In contrast, interictal-like spikes were characterised by an asymmetric overall neuronal discharge initiated by excitatory neurons with the presumptive leading role of bursting pyramidal cells, and possibly terminated by inhibitory interneurons. We found that the overall burstiness of human neocortical neurons is not necessarily related to epilepsy, but the bursting behaviour of excitatory cells comprising both intrinsic and synaptically driven bursting is clearly linked to the generation of epileptiform synchrony.}, year = {2022}, eissn = {2045-2322}, orcid-numbers = {Kandrács, Ágnes/0000-0002-6408-2397; Tóth, Kinga/0000-0002-8751-8499; Erőss, Loránd/0000-0002-5796-5546; Fabó, Dániel/0000-0001-5141-5351; Ulbert, István/0000-0001-9941-9159; Wittner, Lucia/0000-0001-6800-0953} } @article{MTMT:32649994, title = {A covalent strategy to target intrinsically disordered proteins: Discovery of novel tau aggregation inhibitors}, url = {https://m2.mtmt.hu/api/publication/32649994}, author = {Petri, László and Ábrányi-Balogh, Péter and Vagrys, Darius and Imre, Timea and Varró, Nikolett and Mándity, István and Rácz, Anita and Wittner, Lucia and Tóth, Kinga and Tóth, Estilla Zsófia and Juhász, Tünde and Davis, Ben and Keserű, György Miklós}, doi = {10.1016/j.ejmech.2022.114163}, journal-iso = {EUR J MED CHEM}, journal = {EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY}, volume = {231}, unique-id = {32649994}, issn = {0223-5234}, year = {2022}, eissn = {1768-3254}, orcid-numbers = {Petri, László/0000-0001-9881-5096; Vagrys, Darius/0000-0002-8988-9787; Varró, Nikolett/0000-0003-4161-9021; Mándity, István/0000-0003-2865-6143; Wittner, Lucia/0000-0001-6800-0953; Tóth, Kinga/0000-0002-8751-8499} } @article{MTMT:32556740, title = {Perisomatic Inhibition and Its Relation to Epilepsy and to Synchrony Generation in the Human Neocortex}, url = {https://m2.mtmt.hu/api/publication/32556740}, author = {Tóth, Estilla Zsófia and Szabó, Felicia Gyöngyvér and Kandrács, Ágnes and Molnár, Noémi Orsolya and Nagy, Gábor and Bagó, Attila György and Erőss, Loránd and Fabó, Dániel and Hajnal, Boglárka Zsófia and Rácz, Bence and Wittner, Lucia and Ulbert, István and Tóth, Kinga}, doi = {10.3390/ijms23010202}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {32556740}, issn = {1661-6596}, abstract = {Inhibitory neurons innervating the perisomatic region of cortical excitatory principal cells are known to control the emergence of several physiological and pathological synchronous events, including epileptic interictal spikes. In humans, little is known about their role in synchrony generation, although their changes in epilepsy have been thoroughly investigated. This paper demonstraits how parvalbumin (PV)- and type 1 cannabinoid receptor (CB1R)-positive perisomatic interneurons innervate pyramidal cell bodies, and their role in synchronous population events spontaneously emerging in the human epileptic and non-epileptic neocortex, in vitro. Quantitative electron microscopy showed that the overall, PV+ and CB1R+ somatic inhibitory inputs remained unchanged in focal cortical epilepsy. On the contrary, the size of PV-stained synapses increased, and their number decreased in epileptic samples, in synchrony generating regions. Pharmacology demonstrated-in conjunction with the electron microscopy-that although both perisomatic cell types participate, PV+ cells have stronger influence on the generation of population activity in epileptic samples. The somatic inhibitory input of neocortical pyramidal cells remained almost intact in epilepsy, but the larger and consequently more efficient somatic synapses might account for a higher synchrony in this neuron population. This, together with epileptic hyperexcitability, might make a cortical region predisposed to generate or participate in hypersynchronous events.}, year = {2022}, eissn = {1422-0067}, orcid-numbers = {Kandrács, Ágnes/0000-0002-6408-2397; Nagy, Gábor/0000-0001-8831-3340; Erőss, Loránd/0000-0002-5796-5546; Fabó, Dániel/0000-0001-5141-5351; Rácz, Bence/0000-0002-1933-5332; Wittner, Lucia/0000-0001-6800-0953; Ulbert, István/0000-0001-9941-9159; Tóth, Kinga/0000-0002-8751-8499} } @article{MTMT:31951354, title = {Synthesis and characterization of new fluorescent boro-β-carboline dyes}, url = {https://m2.mtmt.hu/api/publication/31951354}, author = {Szepesi Kovács, Dénes and Hajdu, Imre and Mészáros, Gergely and Wittner, Lucia and Meszéna, Domokos and Tóth, Estilla Zsófia and Hegedűs, Zita and Randelovic, Ivan and Tóvári, József and Szabó, Tímea and Szilágyi, Bence and Milen, Mátyás and Keserű, György Miklós and Ábrányi-Balogh, Péter}, doi = {10.1039/D1RA02132J}, journal-iso = {RSC ADV}, journal = {RSC ADVANCES}, volume = {11}, unique-id = {31951354}, issn = {2046-2069}, year = {2021}, eissn = {2046-2069}, pages = {12802-12807}, orcid-numbers = {Wittner, Lucia/0000-0001-6800-0953; Meszéna, Domokos/0000-0003-4042-2542; Tóth, Estilla Zsófia/0000-0003-4732-5796; Randelovic, Ivan/0000-0003-0161-0022; Tóvári, József/0000-0002-5543-3204; Szabó, Tímea/0000-0003-0700-4680; Milen, Mátyás/0000-0002-3538-8872; Keserű, György Miklós/0000-0003-1039-7809; Ábrányi-Balogh, Péter/0000-0002-9284-5160} } @article{MTMT:31256609, title = {The neural tissue around SU-8 implants: A quantitative in vivo biocompatibility study}, url = {https://m2.mtmt.hu/api/publication/31256609}, author = {Márton, Gergely and Tóth, Estilla Zsófia and Wittner, Lucia and Fiáth, Richárd and Pinke, Domonkos Péter and Orbán, Gábor and Meszéna, Domokos and Pál, Ildikó and Győri, Edit Lelle and Bereczki, Zsófia and Kandrács, Ágnes and Hofer, Katharina and Pongrácz, Anita and Ulbert, István and Tóth, Kinga}, doi = {10.1016/j.msec.2020.110870}, journal-iso = {MAT SCI ENG C-MATER}, journal = {MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS}, volume = {112}, unique-id = {31256609}, issn = {0928-4931}, year = {2020}, eissn = {1873-0191}, orcid-numbers = {Wittner, Lucia/0000-0001-6800-0953; Fiáth, Richárd/0000-0001-8732-2691; Orbán, Gábor/0000-0002-8513-626X; Meszéna, Domokos/0000-0003-4042-2542; Pál, Ildikó/0000-0003-2124-9967; Kandrács, Ágnes/0000-0002-6408-2397; Pongrácz, Anita/0000-0001-6793-8739; Ulbert, István/0000-0001-9941-9159; Tóth, Kinga/0000-0002-8751-8499} }