@article{MTMT:34833183, title = {Different states of synaptic vesicle priming explain target cell type–dependent differences in neurotransmitter release}, url = {https://m2.mtmt.hu/api/publication/34833183}, author = {Aldahabi, Mohammad and Neher, Erwin and Nusser, Zoltán}, doi = {10.1073/pnas.2322550121}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {121}, unique-id = {34833183}, issn = {0027-8424}, abstract = {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.}, keywords = {hippocampal interneurons; Synaptic modeling; short-term plasticity; synaptic diversity; active zone}, year = {2024}, eissn = {1091-6490}, orcid-numbers = {Neher, Erwin/0000-0002-9758-7922} } @article{MTMT:34825010, title = {The Dopaminergic Cells in the Median Raphe Region Regulate Social Behavior in Male Mice}, url = {https://m2.mtmt.hu/api/publication/34825010}, author = {Chaves, Tiago and Török, Bibiána and Fazekas, Csilla Lea and Correia, Pedro and Bodóné Sipos, Eszter and Várkonyi, Dorottya and Tóth, Zsuzsanna and Dóra, Fanni and Dobolyi, Árpád and Zelena, Dóra}, doi = {10.3390/ijms25084315}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34825010}, issn = {1661-6596}, abstract = {According to previous studies, the median raphe region (MRR) is known to contribute significantly to social behavior. Besides serotonin, there have also been reports of a small population of dopaminergic neurons in this region. Dopamine is linked to reward and locomotion, but very little is known about its role in the MRR. To address that, we first confirmed the presence of dopaminergic cells in the MRR of mice (immunohistochemistry, RT-PCR), and then also in humans (RT-PCR) using healthy donor samples to prove translational relevance. Next, we used chemogenetic technology in mice containing the Cre enzyme under the promoter of the dopamine transporter. With the help of an adeno-associated virus, designer receptors exclusively activated by designer drugs (DREADDs) were expressed in the dopaminergic cells of the MRR to manipulate their activity. Four weeks later, we performed an extensive behavioral characterization 30 min after the injection of the artificial ligand (Clozapine-N-Oxide). Stimulation of the dopaminergic cells in the MRR decreased social interest without influencing aggression and with an increase in social discrimination. Additionally, inhibition of the same cells increased the friendly social behavior during social interaction test. No behavioral changes were detected in anxiety, memory or locomotion. All in all, dopaminergic cells were present in both the mouse and human samples from the MRR, and the manipulation of the dopaminergic neurons in the MRR elicited a specific social response.}, keywords = {Dopamine; BEHAVIOR; DREADD; Median raphe region}, year = {2024}, eissn = {1422-0067}, orcid-numbers = {Chaves, Tiago/0000-0001-8761-2728; Correia, Pedro/0000-0002-4410-9855; Tóth, Zsuzsanna/0000-0002-0628-1320; Dóra, Fanni/0000-0001-8301-8203; Dobolyi, Árpád/0000-0003-0397-2991} } @misc{MTMT:34780224, title = {Endocannabinoid and neuroplasticity-related changes as susceptibility factors in a rat model of posttraumatic stress disorder.}, url = {https://m2.mtmt.hu/api/publication/34780224}, author = {Szente, László and Balla, Gyula and Varga, Zoltán Kristóf and Blanka, Toth and Bíró, László and Balogh, Zoltán and Matthew, N Hill and Tóth, Máté and Mikics, Éva and Aliczki, Manó}, unique-id = {34780224}, year = {2024}, orcid-numbers = {Balla, Gyula/0009-0007-6449-0773; Balogh, Zoltán/0000-0002-1020-4694} } @misc{MTMT:34780214, title = {Pretrauma cognitive traits predict trauma-induced fear generalization and associated prefrontal functioning in a longitudinal model of posttraumatic stress disorder.}, url = {https://m2.mtmt.hu/api/publication/34780214}, author = {Szente, László and Aliczki, Manó and Balla, Gyula and Róbert, D. Maróthy and Varga, Zoltán Kristóf and Bendegúz, Á. Varga and Borhegyi, Zsolt and Bíró, László and Demeter, Kornél and Miskolczi, Christina and Balogh, Zoltán and Szebik, Huba and Stiftné Szilvásy-Szabó, Anett and Kurilla, Anita and Tóth, Máté and Mikics, Éva}, unique-id = {34780214}, year = {2024}, orcid-numbers = {Balla, Gyula/0009-0007-6449-0773; Borhegyi, Zsolt/0000-0001-5556-8742; Balogh, Zoltán/0000-0002-1020-4694} } @article{MTMT:34753869, title = {CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology}, url = {https://m2.mtmt.hu/api/publication/34753869}, author = {Glavan, Martina and Jelic, Ana and Levard, Damien and Frösen, Juhana and Keränen, Sara and Franx, Bart A. A. and Brás, Ana Rita and Louet, Estelle R. and Dénes, Ádám and Merlini, Mario and Vivien, Denis and Rubio, Marina}, doi = {10.1186/s40478-024-01756-5}, journal-iso = {ACTA NEUROPATH COMM}, journal = {ACTA NEUROPATHOLOGICA COMMUNICATIONS}, volume = {12}, unique-id = {34753869}, issn = {2051-5960}, abstract = {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.}, year = {2024}, eissn = {2051-5960}, orcid-numbers = {Rubio, Marina/0000-0002-6120-4053} } @article{MTMT:34751107, title = {Microglial Inflammatory Mechanisms in Stroke: The Jury Is Still Out}, url = {https://m2.mtmt.hu/api/publication/34751107}, author = {Benkő, Szilvia and Dénes, Ádám}, doi = {10.1016/j.neuroscience.2024.02.007}, journal-iso = {NEUROSCIENCE}, journal = {NEUROSCIENCE}, unique-id = {34751107}, issn = {0306-4522}, abstract = {Microglia represent the main immune cell population in the CNS with unique homeostatic roles and contribution to broad neurological conditions. Stroke is associated with marked changes in microglial phenotypes and induction of inflammatory responses, which emerge as key modulators of brain injury, neurological outcome and regeneration. However, due to the limited availability of functional studies with selective targeting of microglia and microglia-related inflammatory pathways in stroke, the vast majority of observations remain correlative and controversial. Because extensive review articles discussing the role of inflammatory mechanisms in different forms of acute brain injury are available, here we focus on some specific pathways that appear to be important for stroke pathophysiology with assumed contribution by microglia. While the growing toolkit for microglia manipulation increasingly allows targeting inflammatory pathways in a cell-specific manner, reconsideration of some effects devoted to microglia may also be required. This may particularly concern the interpretation of inflammatory mechanisms that emerge in response to stroke as a form of sterile injury and change markedly in chronic inflammation and common stroke comorbidities.}, keywords = {Inflammation; stroke; microglia; Sterile injury; NOD-like receptors (NLRs); cell-specific manipulation}, year = {2024}, eissn = {1873-7544} } @article{MTMT:34751057, title = {Endothelial cells and macrophages as allies in the healthy and diseased brain}, url = {https://m2.mtmt.hu/api/publication/34751057}, author = {Dénes, Ádám and Hansen, Cathrin E. and Oezorhan, Uemit and Figuerola, Sara and de Vries, Helga E. and Sorokin, Lydia and Planas, Anna M. and Engelhardt, Britta and Schwaninger, Markus}, doi = {10.1007/s00401-024-02695-0}, journal-iso = {ACTA NEUROPATHOL}, journal = {ACTA NEUROPATHOLOGICA}, volume = {147}, unique-id = {34751057}, issn = {0001-6322}, abstract = {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.}, year = {2024}, eissn = {1432-0533}, orcid-numbers = {Schwaninger, Markus/0000-0002-4510-9718} } @article{MTMT:34749015, title = {Synaptic and dendritic architecture of different types of hippocampal somatostatin interneurons}, url = {https://m2.mtmt.hu/api/publication/34749015}, author = {Tresóné Takács, Virág and Bardóczi, Zsuzsanna and Orosz, Áron and Major, Ábel and Tar, Luca and Berki, Péter and Papp, Péter and Mayer, Márton István and Sebők, Hunor and Zsolt, Luca and Sós, Katalin Eszter and Káli, Szabolcs and Freund, Tamás and Nyíri, Gábor}, doi = {10.1371/journal.pbio.3002539}, journal-iso = {PLOS BIOL}, journal = {PLOS BIOLOGY}, volume = {22}, unique-id = {34749015}, issn = {1544-9173}, abstract = {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.}, year = {2024}, eissn = {1545-7885}, orcid-numbers = {Tresóné Takács, Virág/0000-0002-3276-4131} } @article{MTMT:34748236, title = {A Molecular Hybrid of the GFP Chromophore and 2,2′-Bipyridine: An Accessible Sensor for Zn2+ Detection with Fluorescence Microscopy}, url = {https://m2.mtmt.hu/api/publication/34748236}, author = {Csomos, Attila and Madarász, Miklós and Turczel, Gábor and Cseri, Levente and Katona, Gergely and Rózsa J., Balázs and Kovács, Ervin and Mucsi, Zoltán}, doi = {10.3390/ijms25063504}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34748236}, issn = {1661-6596}, abstract = {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.}, year = {2024}, eissn = {1422-0067}, orcid-numbers = {Madarász, Miklós/0000-0001-7057-303X; Katona, Gergely/0000-0002-4173-0355; Kovács, Ervin/0000-0002-3939-6925; Mucsi, Zoltán/0000-0003-3224-8847} } @article{MTMT:34724516, title = {A GFP inspired 8-methoxyquinoline-derived fluorescent molecular sensor for the detection of Zn2+ by two-photon microscopy}, url = {https://m2.mtmt.hu/api/publication/34724516}, author = {Csomos, Attila and Madarász, Miklós and Turczel, Gábor and Cseri, Levente and Bodor, Andrea and Anett, Matuscsák and Katona, Gergely and Kovács, Ervin and Rózsa J., Balázs and Mucsi, Zoltán}, doi = {10.1002/chem.202400009}, journal-iso = {CHEM-EUR J}, journal = {CHEMISTRY-A EUROPEAN JOURNAL}, unique-id = {34724516}, issn = {0947-6539}, abstract = {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.}, year = {2024}, eissn = {1521-3765}, orcid-numbers = {Madarász, Miklós/0000-0001-7057-303X; Bodor, Andrea/0000-0002-7422-298X; Katona, Gergely/0000-0002-4173-0355; Kovács, Ervin/0000-0002-3939-6925; Mucsi, Zoltán/0000-0003-3224-8847} }