TY - JOUR AU - Aldahabi, Mohammad AU - Neher, Erwin AU - Nusser, Zoltán TI - Different states of synaptic vesicle priming explain target cell type–dependent differences in neurotransmitter release JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA J2 - P NATL ACAD SCI USA VL - 121 PY - 2024 IS - 18 SN - 0027-8424 DO - 10.1073/pnas.2322550121 UR - https://m2.mtmt.hu/api/publication/34833183 ID - 34833183 AB - Pronounced differences in neurotransmitter release from a given presynaptic neuron, depending on the synaptic target, are among the most intriguing features of cortical networks. Hippocampal pyramidal cells (PCs) release glutamate with low probability to somatostatin expressing oriens-lacunosum-moleculare (O-LM) interneurons (INs), and the postsynaptic responses show robust short-term facilitation, whereas the release from the same presynaptic axons onto fast-spiking INs (FSINs) is ~10-fold higher and the excitatory postsynaptic currents (EPSCs) display depression. The mechanisms underlying these vastly different synaptic behaviors have not been conclusively identified. Here, we applied a combined functional, pharmacological, and modeling approach to address whether the main difference lies in the action potential-evoked fusion or else in upstream priming processes of synaptic vesicles (SVs). A sequential two-step SV priming model was fitted to the peak amplitudes of unitary EPSCs recorded in response to complex trains of presynaptic stimuli in acute hippocampal slices of adult mice. At PC–FSIN connections, the fusion probability (P fusion ) of well-primed SVs is 0.6, and 44% of docked SVs are in a fusion-competent state. At PC–O-LM synapses, P fusion is only 40% lower (0.36), whereas the fraction of well-primed SVs is 6.5-fold smaller. Pharmacological enhancement of fusion by 4-AP and priming by PDBU was recaptured by the model with a selective increase of P fusion and the fraction of well-primed SVs, respectively. Our results demonstrate that the low fidelity of transmission at PC–O-LM synapses can be explained by a low occupancy of the release sites by well-primed SVs. LA - English DB - MTMT ER - TY - GEN AU - Szente, László AU - Balla, Gyula AU - Varga, Zoltán Kristóf AU - Blanka, Toth AU - Bíró, László AU - Balogh, Zoltán AU - Matthew, N Hill AU - Tóth, Máté AU - Mikics, Éva AU - Aliczki, Manó TI - Endocannabinoid and neuroplasticity-related changes as susceptibility factors in a rat model of posttraumatic stress disorder. PY - 2024 UR - https://m2.mtmt.hu/api/publication/34780224 ID - 34780224 LA - English DB - MTMT ER - TY - GEN AU - Szente, László AU - Aliczki, Manó AU - Balla, Gyula AU - Róbert, D. Maróthy AU - Varga, Zoltán Kristóf AU - Bendegúz, Á. Varga AU - Borhegyi, Zsolt AU - Bíró, László AU - Demeter, Kornél AU - Miskolczi, Christina AU - Balogh, Zoltán AU - Szebik, Huba AU - Stiftné Szilvásy-Szabó, Anett AU - Kurilla, Anita AU - Tóth, Máté AU - Mikics, Éva TI - Pretrauma cognitive traits predict trauma-induced fear generalization and associated prefrontal functioning in a longitudinal model of posttraumatic stress disorder. PY - 2024 UR - https://m2.mtmt.hu/api/publication/34780214 ID - 34780214 LA - English DB - MTMT ER - TY - JOUR AU - Glavan, Martina AU - Jelic, Ana AU - Levard, Damien AU - Frösen, Juhana AU - Keränen, Sara AU - Franx, Bart A. A. AU - Brás, Ana Rita AU - Louet, Estelle R. AU - Dénes, Ádám AU - Merlini, Mario AU - Vivien, Denis AU - Rubio, Marina TI - CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology JF - ACTA NEUROPATHOLOGICA COMMUNICATIONS J2 - ACTA NEUROPATH COMM VL - 12 PY - 2024 IS - 1 PG - 23 SN - 2051-5960 DO - 10.1186/s40478-024-01756-5 UR - https://m2.mtmt.hu/api/publication/34753869 ID - 34753869 AB - Intracerebral aneurysms (IAs) are pathological dilatations of cerebral arteries whose rupture leads to subarachnoid hemorrhage, a significant cause of disability and death. Inflammation is recognized as a critical contributor to the formation, growth, and rupture of IAs; however, its precise actors have not yet been fully elucidated. Here, we report CNS-associated macrophages (CAMs), also known as border-associated macrophages, as one of the key players in IA pathogenesis, acting as critical mediators of inflammatory processes related to IA ruptures. Using a new mouse model of middle cerebral artery (MCA) aneurysms we show that CAMs accumulate in the IA walls. This finding was confirmed in a human MCA aneurysm obtained after surgical clipping, together with other pathological characteristics found in the experimental model including morphological changes and inflammatory cell infiltration. In addition, in vivo longitudinal molecular MRI studies revealed vascular inflammation strongly associated with the aneurysm area, i.e., high expression of VCAM-1 and P-selectin adhesion molecules, which precedes and predicts the bleeding extent in the case of IA rupture. Specific CAM depletion by intracerebroventricular injection of clodronate liposomes prior to IA induction reduced IA formation and rupture rate. Moreover, the absence of CAMs ameliorated the outcome severity of IA ruptures resulting in smaller hemorrhages, accompanied by reduced neutrophil infiltration. Our data shed light on the unexplored role of CAMs as main actors orchestrating the progression of IAs towards a rupture-prone state. LA - English DB - MTMT ER - TY - JOUR AU - Benkő, Szilvia AU - Dénes, Ádám TI - Microglial Inflammatory Mechanisms in Stroke: The Jury Is Still Out JF - NEUROSCIENCE J2 - NEUROSCIENCE PY - 2024 SN - 0306-4522 DO - 10.1016/j.neuroscience.2024.02.007 UR - https://m2.mtmt.hu/api/publication/34751107 ID - 34751107 LA - English DB - MTMT ER - TY - JOUR AU - Dénes, Ádám AU - Hansen, Cathrin E. AU - Oezorhan, Uemit AU - Figuerola, Sara AU - de Vries, Helga E. AU - Sorokin, Lydia AU - Planas, Anna M. AU - Engelhardt, Britta AU - Schwaninger, Markus TI - Endothelial cells and macrophages as allies in the healthy and diseased brain JF - ACTA NEUROPATHOLOGICA J2 - ACTA NEUROPATHOL VL - 147 PY - 2024 IS - 1 SN - 0001-6322 DO - 10.1007/s00401-024-02695-0 UR - https://m2.mtmt.hu/api/publication/34751057 ID - 34751057 AB - Diseases of the central nervous system (CNS) are often associated with vascular disturbances or inflammation and frequently both. Consequently, endothelial cells and macrophages are key cellular players that mediate pathology in many CNS diseases. Macrophages in the brain consist of the CNS-associated macrophages (CAMs) [also referred to as border-associated macrophages (BAMs)] and microglia, both of which are close neighbours or even form direct contacts with endothelial cells in microvessels. Recent progress has revealed that different macrophage populations in the CNS and a subset of brain endothelial cells are derived from the same erythromyeloid progenitor cells. Macrophages and endothelial cells share several common features in their life cycle—from invasion into the CNS early during embryonic development and proliferation in the CNS, to their demise. In adults, microglia and CAMs have been implicated in regulating the patency and diameter of vessels, blood flow, the tightness of the blood–brain barrier, the removal of vascular calcification, and the life-time of brain endothelial cells. Conversely, CNS endothelial cells may affect the polarization and activation state of myeloid populations. The molecular mechanisms governing the pas de deux of brain macrophages and endothelial cells are beginning to be deciphered and will be reviewed here. LA - English DB - MTMT ER - TY - JOUR AU - Tresóné Takács, Virág AU - Bardóczi, Zsuzsanna AU - Orosz, Áron AU - Major, Ábel AU - Tar, Luca AU - Berki, Péter AU - Papp, Péter AU - Mayer, Márton István AU - Sebők, Hunor AU - Zsolt, Luca AU - Sós, Katalin Eszter AU - Káli, Szabolcs AU - Freund, Tamás AU - Nyíri, Gábor TI - Synaptic and dendritic architecture of different types of hippocampal somatostatin interneurons JF - PLOS BIOLOGY J2 - PLOS BIOL VL - 22 PY - 2024 IS - 3 PG - 54 SN - 1544-9173 DO - 10.1371/journal.pbio.3002539 UR - https://m2.mtmt.hu/api/publication/34749015 ID - 34749015 AB - GABAergic inhibitory neurons fundamentally shape the activity and plasticity of cortical circuits. A major subset of these neurons contains somatostatin (SOM); these cells play crucial roles in neuroplasticity, learning, and memory in many brain areas including the hippocampus, and are implicated in several neuropsychiatric diseases and neurodegenerative disorders. Two main types of SOM-containing cells in area CA1 of the hippocampus are oriens-lacunosum-moleculare (OLM) cells and hippocampo-septal (HS) cells. These cell types show many similarities in their soma-dendritic architecture, but they have different axonal targets, display different activity patterns in vivo, and are thought to have distinct network functions. However, a complete understanding of the functional roles of these interneurons requires a precise description of their intrinsic computational properties and their synaptic interactions. In the current study we generated, analyzed, and make available several key data sets that enable a quantitative comparison of various anatomical and physiological properties of OLM and HS cells in mouse. The data set includes detailed scanning electron microscopy (SEM)-based 3D reconstructions of OLM and HS cells along with their excitatory and inhibitory synaptic inputs. Combining this core data set with other anatomical data, patch-clamp electrophysiology, and compartmental modeling, we examined the precise morphological structure, inputs, outputs, and basic physiological properties of these cells. Our results highlight key differences between OLM and HS cells, particularly regarding the density and distribution of their synaptic inputs and mitochondria. For example, we estimated that an OLM cell receives about 8,400, whereas an HS cell about 15,600 synaptic inputs, about 16% of which are GABAergic. Our data and models provide insight into the possible basis of the different functionality of OLM and HS cell types and supply essential information for more detailed functional models of these neurons and the hippocampal network. LA - English DB - MTMT ER - TY - JOUR AU - Csomos, Attila AU - Madarász, Miklós AU - Turczel, Gábor AU - Cseri, Levente AU - Katona, Gergely AU - Rózsa J., Balázs AU - Kovács, Ervin AU - Mucsi, Zoltán TI - A Molecular Hybrid of the GFP Chromophore and 2,2′-Bipyridine: An Accessible Sensor for Zn2+ Detection with Fluorescence Microscopy JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 6 PG - 14 SN - 1661-6596 DO - 10.3390/ijms25063504 UR - https://m2.mtmt.hu/api/publication/34748236 ID - 34748236 N1 - Department of Chemistry, Femtonics Ltd, Tűzoltó utca 59, Budapest, H-1094, Hungary Hevesy György PhD School of Chemistry, Eötvös Loránd University, Pázmány Péter sétány 1/A, Budapest, H-1117, Hungary BrainVisionCenter, Liliom utca 43, Budapest, H-1094, Hungary NMR Research Laboratory, HUN-REN Research Centre for Natural Sciences, Magyar Tudósok körútja 2, Budapest, H-1117, Hungary Department of Organic Chemistry & Technology, Budapest University of Technology & Economics, 3. Muegyetem rakpart, Budapest, H-1111, Hungary Two-Photon Measurement Technology Research Group, Pázmány Péter Catholic University, Práter utca 50/a, Budapest, H-1083, Hungary Laboratory of 3D Functional Network and Dendritic Imaging, Institute of Experimental Medicine, Szigony utca 43, Budapest, H-1083, Hungary Polymer Chemistry and Physics Research Group, HUN-REN Research Centre for Natural Sciences, Magyar Tudósok körútja 2, Budapest, H-1117, Hungary Faculty of Materials and Chemical Sciences, University of Miskolc, Miskolc, H-3515, Hungary Export Date: 12 April 2024 Correspondence Address: Rózsa, B.; BrainVisionCenter, Liliom utca 43, Hungary; email: rozsabal@koki.hu Correspondence Address: Kovács, E.; Two-Photon Measurement Technology Research Group, Práter utca 50/a, Hungary; email: kovacs.ervin@ttk.hu AB - The few commercially available chemosensors and published probes for in vitro Zn2+ detection in two-photon microscopy are compromised by their flawed spectroscopic properties, causing issues in selectivity or challenging multistep syntheses. Herein, we present the development of an effective small molecular GFP chromophore-based fluorescent chemosensor with a 2,2′-bipyridine chelator moiety (GFZnP BIPY) for Zn2+ detection that has straightforward synthesis and uncompromised properties. Detailed experimental characterizations of the free and the zinc-bound compounds within the physiologically relevant pH range are presented. Excellent photophysical characteristics are reported, including a 53-fold fluorescence enhancement with excitation and emission maxima at 422 nm and 492 nm, respectively. A high two-photon cross section of 3.0 GM at 840 nm as well as excellent metal ion selectivity are reported. In vitro experiments on HEK 293 cell culture were carried out using two-photon microscopy to demonstrate the applicability of the novel sensor for zinc bioimaging. LA - English DB - MTMT ER - TY - JOUR AU - Csomos, Attila AU - Madarász, Miklós AU - Turczel, Gábor AU - Cseri, Levente AU - Bodor, Andrea AU - Anett, Matuscsák AU - Katona, Gergely AU - Kovács, Ervin AU - Rózsa J., Balázs AU - Mucsi, Zoltán TI - A GFP inspired 8-methoxyquinoline-derived fluorescent molecular sensor for the detection of Zn2+ by two-photon microscopy JF - CHEMISTRY-A EUROPEAN JOURNAL J2 - CHEM-EUR J PY - 2024 SN - 0947-6539 DO - 10.1002/chem.202400009 UR - https://m2.mtmt.hu/api/publication/34724516 ID - 34724516 AB - An effective, GFP-inspired fluorescent Zn2+ sensor is developed for two-photon microscopy and related biological application that featured an 8-methoxyquinoline moiety. Excellent photophysical characteristics including a 37-fold fluorescence enhancement with excitation and emission maxima at 440 nm and 505 nm, respectively, as well as a high two-photon cross-section of 73 GM at 880 nm are reported. Based on the experimental data, the relationship between the structure and properties was elucidated and explained backed up by DFT calculations, particularly to the observed PeT phenomenon for the turn-on process. Biological validation and detailed experimental and theoretical characterization of the free and the zinc-bound compounds are presented. LA - English DB - MTMT ER - TY - JOUR AU - Varga, Viktor AU - Petersen, Peter AU - Zutshi, Ipshita AU - Huszar, Roman AU - Zhang, Yiyao AU - Buzsáki, György TI - Working memory features are embedded in hippocampal place fields JF - CELL REPORTS J2 - CELL REP VL - 43 PY - 2024 IS - 3 SP - 113807 SN - 2211-1247 DO - 10.1016/j.celrep.2024.113807 UR - https://m2.mtmt.hu/api/publication/34714189 ID - 34714189 LA - English DB - MTMT ER -