@article{MTMT:33288877, title = {Different priming states of synaptic vesicles underlie distinct release probabilities at hippocampal excitatory synapses}, url = {https://m2.mtmt.hu/api/publication/33288877}, author = {Aldahabi, Mohammad and Bálint, Flóra and Holderith, Noémi and Lőrincz, Andrea and Reva, Maria and Nusser, Zoltán}, doi = {10.1016/j.neuron.2022.09.035}, journal-iso = {NEURON}, journal = {NEURON}, volume = {110}, unique-id = {33288877}, issn = {0896-6273}, keywords = {hippocampus; physiology; Probability; SYNAPSES; synapse; interneuron; Synaptic Vesicles; synapse vesicle; hippocampal interneurons; interneurons; freeze-fracture replica labeling; synaptic diversity; active zone; molecular composition of the synapse}, year = {2022}, eissn = {1097-4199}, pages = {4144-4161.e7} } @article{MTMT:32720754, title = {Selective Enrichment of Munc13-2 in Presynaptic Active Zones of Hippocampal Pyramidal Cells That Innervate mGluR1α Expressing Interneurons}, url = {https://m2.mtmt.hu/api/publication/32720754}, author = {Holderith, Noémi and Aldahabi, Mohammad and Nusser, Zoltán}, doi = {10.3389/fnsyn.2021.773209}, journal-iso = {FRONT SYNAPTIC NEURO}, journal = {FRONTIERS IN SYNAPTIC NEUROSCIENCE}, volume = {13}, unique-id = {32720754}, keywords = {hippocampus; CA1; O-LM interneuron; paired recordings; multiplexed postembedding immunohistochemistry; vesicle release probability; short-term plasticity}, year = {2022}, eissn = {1663-3563} } @article{MTMT:32256908, title = {Variability in the Munc13-1 content of excitatory release sites}, url = {https://m2.mtmt.hu/api/publication/32256908}, author = {Karlócai, Rita and Herédi, Judit and Benedek, Tünde and Holderith, Noémi and Lőrincz, Andrea and Nusser, Zoltán}, doi = {10.7554/eLife.67468}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {10}, unique-id = {32256908}, issn = {2050-084X}, year = {2021}, eissn = {2050-084X}, orcid-numbers = {Herédi, Judit/0000-0002-8248-3485} } @article{MTMT:31411636, title = {Functional specification of CCK plus interneurons by alternative isoforms of Kv4.3 auxiliary subunits}, url = {https://m2.mtmt.hu/api/publication/31411636}, author = {Oláh, Viktor János and Lukacsovich, David and Winterer, Jochen and Arszovszki, Antónia and Lőrincz, Andrea and Nusser, Zoltán and Foldy, Csaba and Szabadics, János}, doi = {10.7554/eLife.58515}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {9}, unique-id = {31411636}, issn = {2050-084X}, abstract = {CCK-expressing interneurons (CCK+INs) are crucial for controlling hippocampal activity. We found two firing phenotypes of CCK+INs in rat hippocampal CA3 area; either possessing a previously undetected membrane potential-dependent firing or regular firing phenotype, due to different low-voltage-activated potassium currents. These different excitability properties destine the two types for distinct functions, because the former is essentially silenced during realistic 8-15 Hz oscillations. By contrast, the general intrinsic excitability, morphology and gene-profiles of the two types were surprisingly similar. Even the expression of Kv4.3 channels were comparable, despite evidences showing that Kv4.3-mediated currents underlie the distinct firing properties. Instead, the firing phenotypes were correlated with the presence of distinct isoforms of Kv4 auxiliary subunits (KChIP1 vs. KChIP4e and DPP6S). Our results reveal the underlying mechanisms of two previously unknown types of CCK+INs and demonstrate that alternative splicing of few genes, which may be viewed as a minor change in the cells' whole transcriptome, can determine cell-type identity.}, keywords = {POTASSIUM CHANNELS; GABAERGIC NEURONS; calbindin 1}, year = {2020}, eissn = {2050-084X}, orcid-numbers = {Oláh, Viktor János/0000-0002-2069-7525; Nusser, Zoltán/0000-0001-7004-4111; Szabadics, János/0000-0002-4968-2562} } @article{MTMT:31411164, title = {A High-Resolution Method for Quantitative Molecular Analysis of Functionally Characterized Individual Synapses}, url = {https://m2.mtmt.hu/api/publication/31411164}, author = {Holderith, Noémi and Herédi, Judit and Kis, Viktor and Nusser, Zoltán}, doi = {10.1016/j.celrep.2020.107968}, journal-iso = {CELL REP}, journal = {CELL REPORTS}, volume = {32}, unique-id = {31411164}, issn = {2211-1247}, abstract = {Elucidating the molecular mechanisms underlying the functional diversity of synapses requires a high-resolution, sensitive, diffusion-free, quantitative localization method that allows the determination of many proteins in functionally characterized individual synapses. Array tomography permits the quantitative analysis of single synapses but has limited sensitivity, and its application to functionally characterized synapses is challenging. Here, we aim to overcome these limitations by searching the parameter space of different fixation, resin, embedding, etching, retrieval, and elution conditions. Our optimizations reveal that etching epoxy-resin-embedded ultrathin sections with Na-ethanolate and treating them with SDS dramatically increase the labeling efficiency of synaptic proteins. We also demonstrate that this method is ideal for the molecular characterization of individual synapses following paired recordings, two-photon [Ca2+] or glutamate-sensor (iGluSnFR) imaging. This method fills a missing gap in the toolbox of molecular and cellular neuroscience, helping us to reveal how molecular heterogeneity leads to diversity in function.}, year = {2020}, eissn = {2211-1247}, orcid-numbers = {Herédi, Judit/0000-0002-8248-3485} } @article{MTMT:30966766, title = {Distinct Nanoscale Calcium Channel and Synaptic Vesicle Topographies Contribute to the Diversity of Synaptic Function}, url = {https://m2.mtmt.hu/api/publication/30966766}, author = {Rebola, Nelson and Reva, Maria and Kirizs, Tekla and Szoboszlay, Miklós and Lőrincz, Andrea and Moneron, Gael and Nusser, Zoltán and DiGregorio, David A.}, doi = {10.1016/j.neuron.2019.08.014}, journal-iso = {NEURON}, journal = {NEURON}, volume = {104}, unique-id = {30966766}, issn = {0896-6273}, abstract = {The nanoscale topographical arrangement of voltage-gated calcium channels (VGCC) and synaptic vesicles (SVs) determines synaptic strength and plasticity, but whether distinct spatial distributions underpin diversity of synaptic function is unknown. We performed single bouton Ca2+ imaging, Ca2+ chelator competition, immunogold electron microscopic (EM) localization of VGCCs and the active zone (AZ) protein Munc13-1, at two cerebellar synapses. Unexpectedly, we found that weak synapses exhibited 3-fold more VGCCs than strong synapses, while the coupling distance was 5-fold longer. Reaction-diffusion modeling could explain both functional and structural data with two strikingly different nanotopographical motifs: strong synapses are composed of SVs that are tightly coupled (similar to 10 nm) to VGCC clusters, whereas at weak synapses VGCCs were excluded from the vicinity (similar to 50 nm) of docked vesicles. The distinct VGCC-SV topographical motifs also confer differential sensitivity to neuromodulation. Thus, VGCC-SV arrangements are not canonical, and their diversity could underlie functional heterogeneity across CNS synapses.}, year = {2019}, eissn = {1097-4199}, pages = {693-+} } @article{MTMT:30641389, title = {Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca 2+ ] transients in weakly GCaMP6f expressing hippocampal pyramidal cells}, url = {https://m2.mtmt.hu/api/publication/30641389}, author = {Éltes, Tímea and Szoboszlay, Miklós and Kerti-Szigeti, Katalin and Nusser, Zoltán}, doi = {10.1113/JP277681}, journal-iso = {J PHYSIOL-LONDON}, journal = {JOURNAL OF PHYSIOLOGY-LONDON}, volume = {597}, unique-id = {30641389}, issn = {0022-3751}, keywords = {immunohistochemistry; MOUSE; In vitro electrophysiology; two-photon imaging; GCaMP6f; spike inference}, year = {2019}, eissn = {1469-7793}, pages = {2925-2947}, orcid-numbers = {Kerti-Szigeti, Katalin/0000-0001-9500-8758; Nusser, Zoltán/0000-0001-7004-4111} } @article{MTMT:3398234, title = {Creating diverse synapses from the same molecules}, url = {https://m2.mtmt.hu/api/publication/3398234}, author = {Nusser, Zoltán}, doi = {10.1016/j.conb.2018.01.001}, journal-iso = {CURR OPIN NEUROBIOL}, journal = {CURRENT OPINION IN NEUROBIOLOGY}, volume = {51}, unique-id = {3398234}, issn = {0959-4388}, year = {2018}, eissn = {1873-6882}, pages = {8-15} } @article{MTMT:3331601, title = {Objective quantification of nanoscale protein distributions}, url = {https://m2.mtmt.hu/api/publication/3331601}, author = {Szoboszlay, Miklós and Kirizs, Tekla and Nusser, Zoltán}, doi = {10.1038/s41598-017-15695-w}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {7}, unique-id = {3331601}, issn = {2045-2322}, abstract = {Nanoscale distribution of molecules within small subcellular compartments of neurons critically influences their functional roles. Although, numerous ways of analyzing the spatial arrangement of proteins have been described, a thorough comparison of their effectiveness is missing. Here we present an open source software, GoldExt, with a plethora of measures for quantification of the nanoscale distribution of proteins in subcellular compartments (e.g. synapses) of nerve cells. First, we compared the ability of five different measures to distinguish artificial uniform and clustered patterns from random point patterns. Then, the performance of a set of clustering algorithms was evaluated on simulated datasets with predefined number of clusters. Finally, we applied the best performing methods to experimental data, and analyzed the nanoscale distribution of different pre- and postsynaptic proteins, revealing random, uniform and clustered sub-synaptic distribution patterns. Our results reveal that application of a single measure is sufficient to distinguish between different distributions.}, year = {2017}, eissn = {2045-2322} } @article{MTMT:3175581, title = {Target cell type-dependent differences in Ca2+ channel function underlie distinct release probabilities at hippocampal glutamatergic terminals.}, url = {https://m2.mtmt.hu/api/publication/3175581}, author = {Éltes, Tímea and Kirizs, Tekla and Nusser, Zoltán and Holderith, Noémi}, doi = {10.1523/JNEUROSCI.2024-16.2017}, journal-iso = {J NEUROSCI}, journal = {JOURNAL OF NEUROSCIENCE}, volume = {37}, unique-id = {3175581}, issn = {0270-6474}, abstract = {Target cell type-dependent differences in presynaptic release probability (Pr) and short-term plasticity are intriguing features of cortical microcircuits that increase the computational power of neuronal networks. Here we tested the hypothesis that different voltage-gated Ca2+ channel densities in presynaptic active zones (AZs) underlie different Pr Two-photon Ca2+ imaging, triple immunofluorescent labeling and three-dimensional electron microscopic (EM) reconstruction of rat CA3 pyramidal cell axon terminals revealed approximately 1.7 - 1.9-times higher Ca2+inflow per AZ area in high Pr boutons synapsing onto parvalbumin positive interneurons than in low Pr boutons synapsing onto mGluR1alpha positive interneurons. EM replica immunogold labeling, however, demonstrated only 1.15-times larger Cav2.1 and Cav2.2 subunit densities in high Pr AZs. Our results indicate target cell type-specific modulation of voltage-gated Ca2+ channel function or different subunit composition as possible mechanisms underlying the functional differences. In addition, high Pr synapses are also characterized by a higher density of docked vesicles, suggesting that a concerted action of these mechanisms underlies the functional differences. SIGNIFICANCE STATEMENT: Target cell type-dependent variability in presynaptic properties is an intriguing feature of cortical synapses. When a single cortical pyramidal cell establishes a synapse onto a somatostatin-expressing interneuron (IN), the synapse releases glutamate with low probability, whereas the next bouton of the same axon has high release probability when its postsynaptic target is a parvalbumin-expressing IN. Here we used combined molecular, imaging and anatomical approaches to investigate the mechanisms underlying these differences. Our functional experiments implied a approximately 2-fold larger Ca2+ channel density in high release probability boutons whereas freeze-fracture immunolocalization demonstrated only a 15% difference in Ca2+ channel subunit densities. Our results point toward a postsynaptic target cell type-dependent regulation of Ca2+ channel function or different subunit composition as the underlying mechanism.}, year = {2017}, eissn = {1529-2401}, pages = {1910-1924} }