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 - GEN AU - Hegedüs, Panna AU - Victoria, Lyakhova AU - Velencei, Anna AU - Mayer, Márton István AU - Zelenak, Zsofia AU - Nyíri, Gábor AU - Hangya, Balázs TI - Parvalbumin-expressing basal forebrain neurons mediate learning from negative experience PY - 2023 PG - 51 UR - https://m2.mtmt.hu/api/publication/34096335 ID - 34096335 LA - English DB - MTMT ER - TY - JOUR AU - Zichó, Krisztián AU - Sós, Katalin Eszter AU - Papp, Péter AU - Barth, Albert AU - Misák, Erik AU - Orosz, Áron AU - Mayer, Márton István AU - Sebestény, Réka Z. AU - Nyíri, Gábor TI - Fear memory recall involves hippocampal somatostatin interneurons JF - PLOS BIOLOGY J2 - PLOS BIOL VL - 21 PY - 2023 IS - 6 PG - 38 SN - 1544-9173 DO - 10.1371/journal.pbio.3002154 UR - https://m2.mtmt.hu/api/publication/33833304 ID - 33833304 LA - English DB - MTMT ER - TY - JOUR AU - Baksa, Gábor AU - Czeibert, Kálmán AU - Sharp, Veronika AU - Handschuh, Stephan AU - Gyebnár, János AU - Bárány, László AU - Benis, Szabolcs AU - Nyíri, Gábor AU - Mandl, Peter AU - Petneházy, Örs AU - Bálint, Péter Vince TI - Vascular supply of the metacarpophalangeal joint JF - FRONTIERS IN MEDICINE J2 - FRONT MED VL - 9 PY - 2022 PG - 14 SN - 2296-858X DO - 10.3389/fmed.2022.1015895 UR - https://m2.mtmt.hu/api/publication/33190635 ID - 33190635 LA - English DB - MTMT ER - TY - JOUR AU - Sós, Katalin Eszter AU - Mayer, Márton István AU - Tresóné Takács, Virág AU - Major, Ábel AU - Bardóczi, Zsuzsanna AU - Beres, Barnabas M. AU - Szeles, Tamás AU - Saito, Takashi AU - Saido, Takaomi C. AU - Mody, István AU - Freund, Tamás AU - Nyíri, Gábor TI - Amyloid β induces interneuron-specific changes in the hippocampus of APPNL-F mice JF - PLOS ONE J2 - PLOS ONE VL - 15 PY - 2020 IS - 5 PG - 28 SN - 1932-6203 DO - 10.1371/journal.pone.0233700 UR - https://m2.mtmt.hu/api/publication/31337319 ID - 31337319 N1 - Department of Cellular and Network Neurobiology, Institute of Experimental Medicine, HAS, Budapest, Hungary János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary Laboratory for Proteolytic Neuroscience, RIKEN, Center for Brain Science, Saitama, Japan Department of Neurocognitive Science, Nagoya City University Graduate School of Medical Science, Aichi, Japan Department of Neurology, University of California, Los Angeles, CA, United States Cited By :1 Export Date: 14 September 2021 CODEN: POLNC Correspondence Address: Nyiri, G.; Department of Cellular and Network Neurobiology, Hungary; email: nyiri.gabor@koki.mta.hu Chemicals/CAS: amyloid beta protein, 109770-29-8; parvalbumin, 56094-12-3, 83667-75-8; Amyloid beta-Peptides; amyloid beta-protein (1-40); amyloid beta-protein (1-42); Peptide Fragments; Receptors, GABA-A Funding details: 2017-1.2.1-NKP-2017-00002 Funding details: National Institutes of Health, NIH, NS030549 Funding details: Hungarian Scientific Research Fund, OTKA, K119521, NN125643, VKSZ_14-1-2O15-0155 Funding details: Emberi Eroforrások Minisztériuma, EMMI, EFOP-3.6.3-VEKOP-16-2017-00009, UNKP-16-2-I-ELTE-8315/22/2016, UNKP-18-02-I-SE-20 Funding details: National Research, Development and Innovation Office Funding text 1: This work was supported by the U.S. National Institutes of Health (www.nih.gov, NS030549), the National Research, Development and Innovation Office, Hungary (nkfih.gov.hu/forthe-applicants, OTKA K119521, OTKA NN125643, and VKSZ_14-1-2O15-0155) and the Hungarian Brain Research Program (agykutatas.hu, 2017-1.2.1-NKP-2017-00002). The New Nationa Excellence Program of the Ministry of Human Capacities (www.kormany.hu/en/ministry-ofhuman-resources), Hungary supported M.I.M (UNKP-16-2-I-ELTE-8315/22/2016) and A.M. (UNKP-18-02-I-SE-20). K.E.S. was supported by EFOP-3.6.3-VEKOP-16-2017-00009, Development of education of medicine, health and pharmaceutical sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.*%blankline%* LA - English DB - MTMT ER - TY - JOUR AU - Szőnyi, András AU - Zichó, Krisztián AU - Barth, Albert AU - Gönczi, Roland T. AU - Schlingloff, Dániel AU - Török, Bibiána AU - Bodóné Sipos, Eszter AU - Major, Ábel AU - Bardóczi, Zsuzsanna AU - Sós, Katalin Eszter AU - Gulyás, Attila AU - Varga, Viktor AU - Zelena, Dóra AU - Freund, Tamás AU - Nyíri, Gábor TI - Median raphe controls acquisition of negative experience in the mouse JF - SCIENCE J2 - SCIENCE VL - 366 PY - 2019 IS - 6469 PG - 12 SN - 0036-8075 DO - 10.1126/science.aay8746 UR - https://m2.mtmt.hu/api/publication/30881269 ID - 30881269 N1 - * Megosztott szerzőség AB - Adverse events need to be quickly evaluated and memorized, yet how these processes are coordinated is poorly understood. We discovered a large population of excitatory neurons in mouse median raphe region (MRR) expressing vesicular glutamate transporter 2 (vGluT2) that received inputs from several negative experience–related brain centers, projected to the main aversion centers, and activated the septohippocampal system pivotal for learning of adverse events. These neurons were selectively activated by aversive but not rewarding stimuli. Their stimulation induced place aversion, aggression, depression-related anhedonia, and suppression of reward-seeking behavior and memory acquisition–promoting hippocampal theta oscillations. By contrast, their suppression impaired both contextual and cued fear memory formation. These results suggest that MRR vGluT2 neurons are crucial for the acquisition of negative experiences and may play a central role in depression-related mood disorders. © 2019 American Association for the Advancement of Science. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Szőnyi, András AU - Sós, Katalin Eszter AU - Nyilas, Rita AU - Schlingloff, Dániel AU - Domonkos, Andor AU - Tresóné Takács, Virág AU - Pósfai, Balázs AU - Hegedüs, Panna AU - Priestley, James B. AU - Gundlach, Andrew L. AU - Gulyás, Attila AU - Varga, Viktor AU - Losonczy, Attila AU - Freund, Tamás AU - Nyíri, Gábor TI - Brainstem nucleus incertus controls contextual memory formation JF - SCIENCE J2 - SCIENCE VL - 364 PY - 2019 IS - 6442 PG - 13 SN - 0036-8075 DO - 10.1126/science.aaw0445 UR - https://m2.mtmt.hu/api/publication/30725513 ID - 30725513 AB - Hippocampal pyramidal cells encode memory engrams, which guide adaptive behavior. Selection of engram-forming cells is regulated by somatostatin-positive dendrite-targeting interneurons, which inhibit pyramidal cells that are not required for memory formation. Here, we found that gamma-aminobutyric acid ( GABA)-releasing neurons of the mouse nucleus incertus (NI) selectively inhibit somatostatin-positive interneurons in the hippocampus, both monosynaptically and indirectly through the inhibition of their subcortical excitatory inputs. We demonstrated that NI GABAergic neurons receive monosynaptic inputs from brain areas processing important environmental information, and their hippocampal projections are strongly activated by salient environmental inputs in vivo. Optogenetic manipulations of NI GABAergic neurons can shift hippocampal network state and bidirectionally modify the strength of contextual fear memory formation. Our results indicate that brainstem NI GABAergic cells are essential for controlling contextual memories. LA - English DB - MTMT ER - TY - JOUR AU - Wong, Raymond AU - Lénárt, Nikolett AU - Hill, Laura AU - Toms, Lauren AU - Coutts, Graham AU - Martinecz, Bernadett AU - Császár, Eszter AU - Nyíri, Gábor AU - Papaemmanouil, Athina AU - Waisman, Ari AU - Müller, Werner AU - Schwaninger, Markus AU - Rothwell, Nancy AU - Francis, Sheila AU - Pinteaux, Emmanuel AU - Dénes, Ádám AU - Allan, Stuart M. TI - Interleukin-1 mediates ischaemic brain injury via distinct actions on endothelial cells and cholinergic neurons JF - BRAIN BEHAVIOR AND IMMUNITY J2 - BRAIN BEHAV IMMUN VL - 76 PY - 2019 SP - 126 EP - 138 PG - 13 SN - 0889-1591 DO - 10.1016/j.bbi.2018.11.012 UR - https://m2.mtmt.hu/api/publication/30339603 ID - 30339603 N1 - Joint first authors: Raymond Wonga, Nikolett Lénárt Joint senior authors: Emmanuel Pinteauxa, Adam Denés, Stuart M. Allana AB - The cytokine interleukin-1 (IL-1) is a key contributor to neuroinflammation and brain injury, yet mechanisms by which IL-1 triggers neuronal injury remain unknown. Here we induced conditional deletion of IL-1R1 in brain endothelial cells, neurons and blood cells to assess site-specific IL-1 actions in a model of cerebral ischaemia in mice. Tamoxifen treatment of IL-1R1 floxed (fl/fl) mice crossed with mice expressing tamoxifen-inducible Cre-recombinase under the Slco1c1 promoter resulted in brain endothelium-specific deletion of IL-1R1 and a significant decrease in infarct size (29%), blood-brain barrier (BBB) breakdown (53%) and neurological deficit (40%) compared to vehicle-treated or control (IL-1R1fl/fl) mice. Absence of brain endothelial IL-1 signalling improved cerebral blood flow, followed by reduced neutrophil infiltration and vascular activation 24 h after brain injury. Conditional IL-1R1 deletion in neurons using tamoxifen inducible nestin-Cre mice resulted in reduced neuronal injury (25%) and altered microglia-neuron interactions, without affecting cerebral perfusion or vascular activation. Deletion of IL-1R1 specifically in cholinergic neurons reduced infarct size, brain oedema and improved functional outcome. Ubiquitous deletion of IL-1R1 had no effect on brain injury, suggesting beneficial compensatory mechanisms on other cells against the detrimental effects of IL-1 on endothelial cells and neurons. We also show that IL-1R1 signalling deletion in platelets or myeloid cells does not contribute to brain injury after experimental stroke. Thus, brain endothelial and neuronal (cholinergic) IL-1R1 mediate detrimental actions of IL-1 in the brain in ischaemic stroke. Cell-specific targeting of IL-1R1 in the brain could therefore have therapeutic benefits in stroke and other cerebrovascular diseases. LA - English DB - MTMT ER - TY - JOUR AU - Fekete, Csaba AU - Vastagh, Csaba AU - Dénes, Ádám AU - Hrabovszky, Erik AU - Nyíri, Gábor AU - Kalló, Imre AU - Liposits, Zsolt AU - Sárvári, Miklós TI - Chronic Amyloid beta Oligomer Infusion Evokes Sustained Inflammation and Microglial Changes in the Rat Hippocampus via NLRP3. JF - NEUROSCIENCE J2 - NEUROSCIENCE VL - 405 PY - 2019 IS - 1 SP - 35 EP - 46 PG - 12 SN - 0306-4522 DO - 10.1016/j.neuroscience.2018.02.046 UR - https://m2.mtmt.hu/api/publication/3348809 ID - 3348809 N1 - Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, MA 02111, United States “Momentum” Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary Cited By :13 Export Date: 9 September 2021 CODEN: NRSCD Correspondence Address: Sárvári, M.; Department of Endocrine Neurobiology, Szigony u 43., Hungary; email: sarvari.miklos@koki.mta.hu Chemicals/CAS: amyloid beta protein, 109770-29-8; amyloid beta-peptide (1-24); Amyloid beta-Peptides; Cytokines; Furans; Inflammasomes; MCC950; NLR Family, Pyrin Domain-Containing 3 Protein; Nlrp3 protein, rat; Peptide Fragments; Sulfonamides Funding details: Hungarian Scientific Research Fund, OTKA, OTKA 112669, OTKA K115984 Funding details: Magyar Tudományos Akadémia, MTA, LP2016-4/2016 Funding details: National Research, Development and Innovation Office, TP8-005, VKSZ 14-1-2015_0155 Funding text 1: The authors thank Dr. Gábor Mező (Department of Organic Chemistry, Eötvös University, Budapest, Hungary) for his help in the preparation of Aβ 1–42 oligomers, and members of the Behavioral Study Unit of Institute of Experimental Medicine for support in MWM experiments. This work was supported by the National Brain Research Program for CF ( KTIA_13_NAP_A_1/3 ), the ‘Momentum’ Program of Hungarian Academy of Sciences for ÁD (LP2016-4/2016), the Hungarian Scientific Research Fund for EH and ZL ( OTKA 112669 , OTKA K115984 ), the National Research, Development & Innovation Office for GN ( VKSZ 14-1-2015_0155 ) and the Theme Program of Gedeon Richter Plc. for MS ( TP8-005 ). Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, MA 02111, United States “Momentum” Laboratory of Neuroimmunology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary Cited By :13 Export Date: 14 September 2021 CODEN: NRSCD Correspondence Address: Sárvári, M.; Department of Endocrine Neurobiology, Szigony u 43., Hungary; email: sarvari.miklos@koki.mta.hu Chemicals/CAS: amyloid beta protein, 109770-29-8; amyloid beta-peptide (1-24); Amyloid beta-Peptides; Cytokines; Furans; Inflammasomes; MCC950; NLR Family, Pyrin Domain-Containing 3 Protein; Nlrp3 protein, rat; Peptide Fragments; Sulfonamides Funding details: Hungarian Scientific Research Fund, OTKA, OTKA 112669, OTKA K115984 Funding details: Magyar Tudományos Akadémia, MTA, LP2016-4/2016 Funding details: National Research, Development and Innovation Office, TP8-005, VKSZ 14-1-2015_0155 Funding text 1: The authors thank Dr. Gábor Mező (Department of Organic Chemistry, Eötvös University, Budapest, Hungary) for his help in the preparation of Aβ 1–42 oligomers, and members of the Behavioral Study Unit of Institute of Experimental Medicine for support in MWM experiments. This work was supported by the National Brain Research Program for CF ( KTIA_13_NAP_A_1/3 ), the ‘Momentum’ Program of Hungarian Academy of Sciences for ÁD (LP2016-4/2016), the Hungarian Scientific Research Fund for EH and ZL ( OTKA 112669 , OTKA K115984 ), the National Research, Development & Innovation Office for GN ( VKSZ 14-1-2015_0155 ) and the Theme Program of Gedeon Richter Plc. for MS ( TP8-005 ). AB - Microglia are instrumental for recognition and elimination of amyloid beta1-42 oligomers (AbetaOs), but the long-term consequences of AbetaO-induced inflammatory changes in the brain are unclear. Here, we explored microglial responses and transciptome-level inflammatory signatures in the rat hippocampus after chronic AbetaO challenge. Middle-aged Long Evans rats received intracerebroventricular infusion of AbetaO or vehicle for 4weeks, followed by treatment with artificial CSF or MCC950 for the subsequent 4weeks. AbetaO infusion evoked a sustained inflammatory response including activation of NF-kappaB, triggered microglia activation and increased the expression of pattern recognition and phagocytic receptors. Abeta1-42 plaques were not detectable likely due to microglial elimination of infused oligomers. In addition, we found upregulation of neuronal inhibitory ligands and their cognate microglial receptors, while downregulation of Esr1 and Scn1a, encoding estrogen receptor alpha and voltage-gated sodium-channel Na(v)1.1, respectively, was observed. These changes were associated with impaired hippocampus-dependent spatial memory and resembled early neurological changes seen in Alzheimer's disease. To investigate the role of inflammatory actions in memory deterioration, we performed MCC950 infusion, which specifically blocks the NLRP3 inflammasome. MCC950 attenuated AbetaO-evoked microglia reactivity, restored expression of neuronal inhibitory ligands, reversed downregulation of ERalpha, and abolished memory impairments. Furthermore, MCC950 abrogated AbetaO-invoked reduction of serum IL-10. These findings provide evidence that in response to AbetaO infusion microglia change their phenotype, but the resulting inflammatory changes are sustained for at least one month after the end of AbetaO challenge. Lasting NLRP3-driven inflammatory alterations and altered hippocampal gene expression contribute to spatial memory decline. LA - English DB - MTMT ER - TY - JOUR AU - Balázsfi, Diána AU - Zelena, Dóra AU - Demeter, Kornél AU - Miskolczi, Christina AU - Varga, Zoltán Kristóf AU - Nagyvaradi, A AU - Nyíri, Gábor AU - Cserép, Csaba AU - Baranyi, Mária AU - Sperlágh, Beáta AU - Haller, József TI - Differential Roles of the Two Raphe Nuclei in Amiable Social Behavior and Aggression - An Optogenetic Study JF - FRONTIERS IN BEHAVIORAL NEUROSCIENCE J2 - FRONT BEHAV NEUROSCI VL - 12 PY - 2018 PG - 16 SN - 1662-5153 DO - 10.3389/fnbeh.2018.00163 UR - https://m2.mtmt.hu/api/publication/3406802 ID - 3406802 N1 - Laboratory of Behavioural and Stress Studies, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary János Szentágothai School of Neurosciences, Semmelweis University, Budapest, Hungary Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Institute of Behavioural Sciences and Law Enforcement, National University of Public Service, Budapest, Hungary Cited By :18 Export Date: 27 October 2023 Correspondence Address: Haller, J.; Laboratory of Behavioural and Stress Studies, Hungary; email: haller.jozsef@koki.mta.hu Chemicals/CAS: 4 aminobutyric acid, 28805-76-7, 56-12-2; glutamic acid, 11070-68-1, 138-15-8, 56-86-0, 6899-05-4; serotonin, 50-67-9 Funding details: Seventh Framework Programme, FP7, 294313 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, 112907, 120311, ERC-2011-ADG-294313, KÖFOP-2.1.2-VEKOP-15-2016-00001 Funding text 1: This study was supported by NKFIH grant no. 112907, ERC-2011-ADG-294313 (SERRACO), and KÖFOP-2.1.2-VEKOP-15-2016-00001 (all to JH) as well as NKFIH grant no. 120311 to DZ. The agencies had no further role in study design, in the collection, analysis or interpretation of the data. AB - Serotonergic mechanisms hosted by raphe nuclei have important roles in affiliative and agonistic behaviors but the separate roles of the two nuclei are poorly understood. Here we studied the roles of the dorsal (DR) and median raphe region (MRR) in aggression by optogenetically stimulating the two nuclei. Mice received three 3 min-long stimulations, which were separated by non-stimulation periods of 3 min. The stimulation of the MRR decreased aggression in a phasic-like manner. Effects were rapidly expressed during stimulations, and vanished similarly fast when stimulations were halted. No carryover effects were observed in the subsequent three trials performed at 2-day intervals. No effects on social behaviors were observed. By contrast, DR stimulation rapidly and tonically promoted social behaviors: effects were present during both the stimulation and non-stimulation periods of intermittent stimulations. Aggressive behaviors were marginally diminished by acute DR stimulations, but repeated stimulations administered over 8 days considerably decreased aggression even in the absence of concurrent stimulations, indicating the emergence of carryover effects. No such effects were observed in the case of social behaviors. We also investigated stimulation-induced neurotransmitter release in the prefrontal cortex, a major site of aggression control. MRR stimulation rapidly but transiently increased serotonin release, and induced a lasting increase in glutamate levels. DR stimulation had no effect on glutamate, but elicited a lasting increase of serotonin release. Prefrontal serotonin levels remained elevated for at least 2 h subsequent to DR stimulations. The stimulation of both nuclei increased GABA release rapidly and transiently. Thus, differential behavioral effects of the two raphe nuclei were associated with differences in their neurotransmission profiles. These findings reveal a surprisingly strong behavioral task division between the two raphe nuclei, which was associated with a nucleus-specific neurotransmitter release in the prefrontal cortex. LA - English DB - MTMT ER -