@article{MTMT:32660835, title = {Hippocampal sharp wave-ripples and the associated sequence replay emerge from structured synaptic interactions in a network model of area CA3}, url = {https://m2.mtmt.hu/api/publication/32660835}, author = {Ecker, András and Bagi, Bence and Vértes, Eszter and Steinbach-Németh, Orsolya and Karlócai, Rita and Papp, Orsolya I and Miklós, István and Hájos, Norbert and Freund, Tamás and Gulyás, Attila and Káli, Szabolcs}, doi = {10.7554/eLife.71850}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {11}, unique-id = {32660835}, issn = {2050-084X}, abstract = {Hippocampal place cells are activated sequentially as an animal explores its environment. These activity sequences are internally recreated ('replayed'), either in the same or reversed order, during bursts of activity (sharp wave-ripples [SWRs]) that occur in sleep and awake rest. SWR-associated replay is thought to be critical for the creation and maintenance of long-term memory. In order to identify the cellular and network mechanisms of SWRs and replay, we constructed and simulated a data-driven model of area CA3 of the hippocampus. Our results show that the chain-like structure of recurrent excitatory interactions established during learning not only determines the content of replay, but is essential for the generation of the SWRs as well. We find that bidirectional replay requires the interplay of the experimentally confirmed, temporally symmetric plasticity rule, and cellular adaptation. Our model provides a unifying framework for diverse phenomena involving hippocampal plasticity, representations, and dynamics, and suggests that the structured neural codes induced by learning may have greater influence over cortical network states than previously appreciated.}, keywords = {hippocampus; MOUSE; Computational modeling; place cell; spike-timing-dependent plasticity; sequence replay}, year = {2022}, eissn = {2050-084X}, orcid-numbers = {Ecker, András/0000-0001-9635-4169; Gulyás, Attila/0000-0003-4961-636X} } @article{MTMT:32636201, title = {The NKCC1 ion transporter modulates microglial phenotype and inflammatory response to brain injury in a cell-autonomous manner}, url = {https://m2.mtmt.hu/api/publication/32636201}, author = {Tóth, Krisztina and Lénárt, Nikolett and Berki, Péter and Fekete, Rebeka and Cserépné Szabadits, Eszter and Pósfai, Balázs and Cserép, Csaba and Alatshan, Ahmad and Benkő, Szilvia and Kiss, Dániel and Hübner, Christian A. and Gulyás, Attila and Kaila, Kai and Környei, Zsuzsanna and Dénes, Ádám}, doi = {10.1371/journal.pbio.3001526}, journal-iso = {PLOS BIOL}, journal = {PLOS BIOLOGY}, volume = {20}, unique-id = {32636201}, issn = {1544-9173}, abstract = {The NKCC1 ion transporter contributes to the pathophysiology of common neurological disorders, but its function in microglia, the main inflammatory cells of the brain, has remained unclear to date. Therefore, we generated a novel transgenic mouse line in which microglial NKCC1 was deleted. We show that microglial NKCC1 shapes both baseline and reactive microglia morphology, process recruitment to the site of injury, and adaptation to changes in cellular volume in a cell-autonomous manner via regulating membrane conductance. In addition, microglial NKCC1 deficiency results in NLRP3 inflammasome priming and increased production of interleukin-1β (IL-1β), rendering microglia prone to exaggerated inflammatory responses. In line with this, central (intracortical) administration of the NKCC1 blocker, bumetanide, potentiated intracortical lipopolysaccharide (LPS)-induced cytokine levels. In contrast, systemic bumetanide application decreased inflammation in the brain. Microglial NKCC1 KO animals exposed to experimental stroke showed significantly increased brain injury, inflammation, cerebral edema, and, worse, neurological outcome. Thus, NKCC1 emerges as an important player in controlling microglial ion homeostasis and inflammatory responses through which microglia modulate brain injury. The contribution of microglia to central NKCC1 actions is likely to be relevant for common neurological disorders.}, keywords = {Inflammation; MICROGLIAL CELLS; Cytokines; SPLEEN; edema; brain damage; membrane potential; Intraperitoneal injections}, year = {2022}, eissn = {1545-7885}, orcid-numbers = {Lénárt, Nikolett/0000-0002-7456-949X; Pósfai, Balázs/0000-0003-1035-565X; Cserép, Csaba/0000-0001-5513-2471; Kiss, Dániel/0000-0002-8482-8862; Gulyás, Attila/0000-0003-4961-636X; Kaila, Kai/0000-0003-0668-5955} } @article{MTMT:31627527, title = {Distinct synchronization, cortical coupling and behavioral function of two basal forebrain cholinergic neuron types (vol 93, pg 513, 2020)}, url = {https://m2.mtmt.hu/api/publication/31627527}, author = {Laszlovszky, Tamás Kristóf and Schlingloff, Dániel and Hegedüs, Panna and Freund, Tamás and Gulyás, Attila and Kepecs, Adam and Hangya, Balázs}, doi = {10.1038/s41593-020-0702-y}, journal-iso = {NAT NEUROSCI}, journal = {NATURE NEUROSCIENCE}, volume = {23}, unique-id = {31627527}, issn = {1097-6256}, year = {2020}, eissn = {1546-1726}, pages = {1310-1310}, orcid-numbers = {Hegedüs, Panna/0000-0002-9984-5729; Gulyás, Attila/0000-0003-4961-636X; Kepecs, Adam/0000-0003-0049-8120} } @article{MTMT:31357306, title = {Distinct synchronization, cortical coupling and behavioral function of two basal forebrain cholinergic neuron types}, url = {https://m2.mtmt.hu/api/publication/31357306}, author = {Laszlovszky, Tamás Kristóf and Schlingloff, Dániel and Hegedüs, Panna and Freund, Tamás and Gulyás, Attila and Kepecs, Adam and Hangya, Balázs}, doi = {10.1038/s41593-020-0648-0}, journal-iso = {NAT NEUROSCI}, journal = {NATURE NEUROSCIENCE}, volume = {23}, unique-id = {31357306}, issn = {1097-6256}, abstract = {Basal forebrain cholinergic neurons (BFCNs) modulate synaptic plasticity, cortical processing, brain states and oscillations. However, whether distinct types of BFCNs support different functions remains unclear. Therefore, we recorded BFCNs in vivo, to examine their behavioral functions, and in vitro, to study their intrinsic properties. We identified two distinct types of BFCNs that differ in their firing modes, synchronization properties and behavioral correlates. Bursting cholinergic neurons (Burst-BFCNs) fired synchronously, phase-locked to cortical theta activity and fired precisely timed bursts after reward and punishment. Regular-firing cholinergic neurons (Reg-BFCNs) were found predominantly in the posterior basal forebrain, displayed strong theta rhythmicity and responded with precise single spikes after behavioral outcomes. In an auditory detection task, synchronization of Burst-BFCNs to the auditory cortex predicted the timing of behavioral responses, whereas tone-evoked cortical coupling of Reg-BFCNs predicted correct detections. We propose that differential recruitment of two basal forebrain cholinergic neuron types generates behavior-specific cortical activation.}, year = {2020}, eissn = {1546-1726}, pages = {992-1003}, orcid-numbers = {Hegedüs, Panna/0000-0002-9984-5729; Gulyás, Attila/0000-0003-4961-636X} } @article{MTMT:30881269, title = {Median raphe controls acquisition of negative experience in the mouse}, url = {https://m2.mtmt.hu/api/publication/30881269}, author = {Szőnyi, András and Zichó, Krisztián and Barth, Albert and Gönczi, Roland T. and Schlingloff, Dániel and Török, Bibiána and Bodóné Sipos, Eszter and Major, Ábel and Bardóczi, Zsuzsanna and Sós, Katalin Eszter and Gulyás, Attila and Varga, Viktor and Zelena, Dóra and Freund, Tamás and Nyíri, Gábor}, doi = {10.1126/science.aay8746}, journal-iso = {SCIENCE}, journal = {SCIENCE}, volume = {366}, unique-id = {30881269}, issn = {0036-8075}, abstract = {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.}, year = {2019}, eissn = {1095-9203}, orcid-numbers = {Gulyás, Attila/0000-0003-4961-636X} } @article{MTMT:30725513, title = {Brainstem nucleus incertus controls contextual memory formation}, url = {https://m2.mtmt.hu/api/publication/30725513}, author = {Szőnyi, András and Sós, Katalin Eszter and Nyilas, Rita and Schlingloff, Dániel and Domonkos, Andor and Tresóné Takács, Virág and Pósfai, Balázs and Hegedüs, Panna and Priestley, James B. and Gundlach, Andrew L. and Gulyás, Attila and Varga, Viktor and Losonczy, Attila and Freund, Tamás and Nyíri, Gábor}, doi = {10.1126/science.aaw0445}, journal-iso = {SCIENCE}, journal = {SCIENCE}, volume = {364}, unique-id = {30725513}, issn = {0036-8075}, abstract = {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.}, year = {2019}, eissn = {1095-9203}, orcid-numbers = {Nyilas, Rita/0000-0002-9634-9535; Tresóné Takács, Virág/0000-0002-3276-4131; Pósfai, Balázs/0000-0003-1035-565X; Hegedüs, Panna/0000-0002-9984-5729; Gulyás, Attila/0000-0003-4961-636X} } @article{MTMT:3399510, title = {Co-transmission of acetylcholine and GABA regulates hippocampal states}, url = {https://m2.mtmt.hu/api/publication/3399510}, author = {Tresóné Takács, Virág and Cserép, Csaba and Schlingloff, Dániel and Pósfai, Balázs and Szőnyi, András and Sós, Katalin Eszter and Környei, Zsuzsanna and Dénes, Ádám and Gulyás, Attila and Freund, Tamás and Nyíri, Gábor}, doi = {10.1038/s41467-018-05136-1}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {9}, unique-id = {3399510}, issn = {2041-1723}, abstract = {The basal forebrain cholinergic system is widely assumed to control cortical functions via non-synaptic transmission of a single neurotransmitter. Yet, we find that mouse hippocampal cholinergic terminals invariably establish GABAergic synapses, and their cholinergic vesicles dock at those synapses only. We demonstrate that these synapses do not co-release but co-transmit GABA and acetylcholine via different vesicles, whose release is triggered by distinct calcium channels. This co-transmission evokes composite postsynaptic potentials, which are mutually cross-regulated by presynaptic autoreceptors. Although postsynaptic cholinergic receptor distribution cannot be investigated, their response latencies suggest a focal, intra- and/or peri-synaptic localisation, while GABAA receptors are detected intra-synaptically. The GABAergic component alone effectively suppresses hippocampal sharp wave-ripples and epileptiform activity. Therefore, the differentially regulated GABAergic and cholinergic co-transmission suggests a hitherto unrecognised level of control over cortical states. This novel model of hippocampal cholinergic neurotransmission may lead to alternative pharmacotherapies after cholinergic deinnervation seen in neurodegenerative disorders.}, year = {2018}, eissn = {2041-1723}, orcid-numbers = {Tresóné Takács, Virág/0000-0002-3276-4131; Cserép, Csaba/0000-0001-5513-2471; Pósfai, Balázs/0000-0003-1035-565X; Gulyás, Attila/0000-0003-4961-636X} } @article{MTMT:3183697, title = {The Effects of Realistic Synaptic Distribution and 3D Geometry on Signal Integration and Extracellular Field Generation of Hippocampal Pyramidal Cells and Inhibitory Neurons.}, url = {https://m2.mtmt.hu/api/publication/3183697}, author = {Gulyás, Attila and Freund, Tamás and Káli, Szabolcs}, doi = {10.3389/fncir.2016.00088}, journal-iso = {FRONT NEURAL CIRCUIT}, journal = {FRONTIERS IN NEURAL CIRCUITS}, volume = {10}, unique-id = {3183697}, issn = {1662-5110}, abstract = {In vivo and in vitro multichannel field and somatic intracellular recordings are frequently used to study mechanisms of network pattern generation. When interpreting these data, neurons are often implicitly considered as electrotonically compact cylinders with a homogeneous distribution of excitatory and inhibitory inputs. However, the actual distributions of dendritic length, diameter, and the densities of excitatory and inhibitory input are non-uniform and cell type-specific. We first review quantitative data on the dendritic structure and synaptic input and output distribution of pyramidal cells (PCs) and interneurons in the hippocampal CA1 area. Second, using multicompartmental passive models of four different types of neurons, we quantitatively explore the effect of differences in dendritic structure and synaptic distribution on the errors and biases of voltage clamp measurements of inhibitory and excitatory postsynaptic currents. Finally, using the 3-dimensional distribution of dendrites and synaptic inputs we calculate how different inhibitory and excitatory inputs contribute to the generation of local field potential in the hippocampus. We analyze these effects at different realistic background activity levels as synaptic bombardment influences neuronal conductance and thus the propagation of signals in the dendritic tree. We conclude that, since dendrites are electrotonically long and entangled in 3D, somatic intracellular and field potential recordings miss the majority of dendritic events in some cell types, and thus overemphasize the importance of perisomatic inhibitory inputs and belittle the importance of complex dendritic processing. Modeling results also suggest that PCs and inhibitory neurons probably use different input integration strategies. In PCs, second- and higher-order thin dendrites are relatively well-isolated from each other, which may support branch-specific local processing as suggested by studies of active dendritic integration. In the electrotonically compact parvalbumin- and cholecystokinincontaining interneurons, synaptic events are visible in the whole dendritic arbor, and thus the entire dendritic tree may form a single integrative element. Calretinin-containing interneurons were found to be electrotonically extended, which suggests the possibility of complex dendritic processing in this cell type. Our results also highlight the need for the integration of methods that allow the measurement of dendritic processes into studies of synaptic interactions and dynamics in neural networks.}, year = {2016}, eissn = {1662-5110}, orcid-numbers = {Gulyás, Attila/0000-0003-4961-636X} } @article{MTMT:3078169, title = {Properties and dynamics of inhibitory synaptic communication within the CA3 microcircuits of pyramidal cells and interneurons expressing parvalbumin or cholecystokinin}, url = {https://m2.mtmt.hu/api/publication/3078169}, author = {Kohus, Zsolt and Káli, Szabolcs and Rovira Esteban, Laura and Schlingloff, Dániel and Papp, Orsolya and Freund, Tamás and Hájos, Norbert and Gulyás, Attila}, doi = {10.1113/JP272231}, journal-iso = {J PHYSIOL-LONDON}, journal = {JOURNAL OF PHYSIOLOGY-LONDON}, volume = {594}, unique-id = {3078169}, issn = {0022-3751}, abstract = {Different hippocampal activity patterns are determined primarily by the interaction of excitatory cells and different types of interneurons. To understand the mechanisms underlying the generation of different network dynamics the properties of synaptic transmission need to be uncovered. Perisomatic inhibition has been shown to be critical for the generation of sharp wave-ripples, gamma oscillations as well as pathological epileptic activities. Therefore, we decided to quantitatively and systematically characterize the temporal properties of the synaptic transmission between perisomatic inhibitory neurons and pyramidal cells in the CA3 area of mouse hippocampal slices, using action potential patterns recorded during physiological and pathological network states. PV+ and CCK+ interneurons had distinct intrinsic physiological features. Interneurons of the same type formed reciprocally connected subnetworks, while the connectivity between interneuron classes was sparse. The characteristics of unitary interactions depended on the identity of both synaptic partners, while the short-term plasticity of synaptic transmission depended mainly on the presynaptic cell type. PV+ interneurons showed frequency-dependent depression, while more complex dynamics characterized the output of CCK+ interneurons. We quantitatively captured the dynamics of transmission at these different types of connection with simple mathematical models, and described in detail the response to physiological and pathological discharge patterns. Our data suggest that the temporal propeties of PV+ interneuron transmission may contribute to sharp wave-ripple generation. These findings support the view that intrinsic and synaptic features of PV+ cells make them ideally suited for the generation of physiological network oscillations, while CCK+ cells implement more subtle, graded control in the hippocampus. This article is protected by copyright. All rights reserved.}, year = {2016}, eissn = {1469-7793}, pages = {3745-3774}, orcid-numbers = {Kohus, Zsolt/0000-0002-2153-615X; Gulyás, Attila/0000-0003-4961-636X} } @article{MTMT:2719984, title = {Generation of physiological and pathological high frequency oscillations: the role of perisomatic inhibition in sharp-wave ripple and interictal spike generation.}, url = {https://m2.mtmt.hu/api/publication/2719984}, author = {Gulyás, Attila and Freund, Tamás}, doi = {10.1016/j.conb.2014.07.020}, journal-iso = {CURR OPIN NEUROBIOL}, journal = {CURRENT OPINION IN NEUROBIOLOGY}, volume = {31}, unique-id = {2719984}, issn = {0959-4388}, abstract = {Sharp-wave-ripple complexes (SWRs) and interictal-spikes are physiological and pathological forms of irregularly occurring transient high activity events in the hippocampal EEG. They share similar features and carry high-frequency oscillations with different spectral features. Recent results reveal similarities and differences in the generation of the two types of transients, and argue that parvalbumin containing basket cells (PVBCs) are crucial in synchronizing neuronal activity in both cases. SWRs are generated in the reciprocally connected network of inhibitory PVBCs, while in the pathological case, synchronous failure of perisomatic inhibition triggers massive pyramidal cell burst firing. While physiological ripple oscillation is primarily the result of phasic perisomatic inhibitory currents, pathological high-frequency ripples are population spikes of partially synchronous, massively bursting, uninhibited pyramidal cells.}, year = {2015}, eissn = {1873-6882}, pages = {26-32}, orcid-numbers = {Gulyás, Attila/0000-0003-4961-636X} }