92 results on '"Attila Losonczy"'
Search Results
52. Impaired hippocampal place cell dynamics in a mouse model of the 22q11.2 deletion
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Zhenrui Liao, Andres Grosmark, Fraser T. Sparks, Patrick Kaifosh, Joseph A. Gogos, Anastasia Diamantopoulou, Attila Losonczy, Nathan Danielson, John C. Bowler, and Jeffrey D. Zaremba
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Male ,0301 basic medicine ,Place cell ,Hippocampus ,Mice, Transgenic ,Biology ,Hippocampal formation ,Article ,Mice ,Random Allocation ,03 medical and health sciences ,0302 clinical medicine ,DiGeorge Syndrome ,medicine ,Animals ,Humans ,Learning ,Episodic memory ,Recall ,General Neuroscience ,Cognitive flexibility ,Cognition ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Place Cells ,Schizophrenia ,Female ,Goals ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Hippocampal place cells represent the cellular substrate of episodic memory. Place cell ensembles reorganize to support learning but must also maintain stable representations to facilitate memory recall. Despite extensive research, the learning-related role of place cell dynamics in health and disease remains elusive. Using chronic two-photon Ca2+ imaging in hippocampal area CA1 of wild-type and Df(16)A+/− mice, an animal model of 22q11.2 deletion syndrome, one of the most common genetic risk factors for cognitive dysfunction and schizophrenia, we found that goal-oriented learning in wild-type mice was supported by stable spatial maps and robust remapping of place fields toward the goal location. Df(16)A+/− mice showed a significant learning deficit accompanied by reduced spatial map stability and the absence of goal-directed place cell reorganization. These results expand our understanding of the hippocampal ensemble dynamics supporting cognitive flexibility and demonstrate their importance in a model of 22q11.2-associated cognitive dysfunction.
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- 2017
53. Brainstem nucleus incertus controls contextual memory formation
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Panna Hegedüs, Balázs Pósfai, Viktor Sebestyén Varga, Virág T. Takács, Tamás F. Freund, Dániel Schlingloff, Attila I. Gulyás, Andor Domonkos, Rita Nyilas, James B. Priestley, Attila Losonczy, Katalin E. Sos, Gábor Nyiri, Andrew L. Gundlach, and András Szőnyi
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Male ,Hippocampus ,Engram ,Optogenetics ,Hippocampal formation ,Memory and Learning Tests ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Interneurons ,Animals ,GABAergic Neurons ,Theta Rhythm ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Chemistry ,Pyramidal Cells ,Association Learning ,Neural Inhibition ,Nucleus Incertus ,Mice, Inbred C57BL ,Excitatory postsynaptic potential ,GABAergic ,Raphe Nuclei ,Female ,Brainstem ,Somatostatin ,Neuroscience ,030217 neurology & neurosurgery ,Brain Stem - Abstract
What inhibits the inhibitors? In the hippocampus, each memory trace is encoded by a specific subset of pyramidal cells. The other pyramidal cells must be actively excluded from the memory encoding process by inhibition, which is done by selective dendrite-targeting interneurons. Szőnyi et al. found that γ-aminobutyric acid–releasing (GABAergic) cells located in a small region in the brain stem called the nucleus incertus project to the hippocampus. The nucleus incertus again is innervated by several regions that respond to salient stimuli. Its GABAergic cells preferentially inhibit the dendrite-targeting interneurons in the hippocampus. The nucleus incertus is thus a central mediator between brain regions that are highly responsive to salient stimuli and the hippocampal circuitry involved in memory formation. Science , this issue p. eaaw0445
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- 2019
54. Hippocampal network reorganization underlies the formation of a temporal association memory
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Fabio Stefanini, Luca Mazzucato, James B. Priestley, Elizabeth M. Balough, Erin Lavoie, Mohsin Ahmed, Attila Losonczy, Angel Castro, and Stefano Fusi
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0303 health sciences ,education.field_of_study ,Working memory ,Population ,Hippocampus ,Hippocampal formation ,03 medical and health sciences ,0302 clinical medicine ,Fear conditioning ,Aversive Stimulus ,Psychology ,education ,Association (psychology) ,Neuroscience ,Episodic memory ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
Episodic memory requires linking events in time, a function dependent on the hippocampus. In “trace” fear conditioning, animals learn to associate a neutral cue with an aversive stimulus despite their separation in time by a delay period on the order of tens of seconds. But how this temporal association forms remains unclear. Here we use 2-photon calcium imaging to track neural population dynamics over the complete time-course of learning and show that, in contrast to previous theories, the hippocampus does not generate persistent activity to bridge the time delay. Instead, learning is concomitant with broad changes in the active neural population in CA1. While neural responses were highly stochastic in time, cue identity could be reliably read out from population activity rates over longer timescales after learning. These results question the ubiquity of neural sequences during temporal association learning, and suggest that trace fear conditioning relies on mechanisms that differ from persistent activity accounts of working memory.
- Published
- 2019
- Full Text
- View/download PDF
55. Artificial neural networks in action for an automated cell-type classification of biological neural networks
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Panayiota Poirazi, Panagiotis Tsakalides, Grigorios Tsagkatakis, Wen-Ke Li, Gergely F. Turi, Eirini Troullinou, Attila Losonczy, and Spyridon Chavlis
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FOS: Computer and information sciences ,Cell type ,Control and Optimization ,Artificial neural network ,business.industry ,Computer science ,Deep learning ,Feature extraction ,Computer Science - Neural and Evolutionary Computing ,Machine learning ,computer.software_genre ,Class (biology) ,Computer Science Applications ,Data modeling ,Computational Mathematics ,Action (philosophy) ,Artificial Intelligence ,Quantitative Biology - Neurons and Cognition ,FOS: Biological sciences ,Identification (biology) ,Neurons and Cognition (q-bio.NC) ,Artificial intelligence ,Neural and Evolutionary Computing (cs.NE) ,business ,computer - Abstract
Identification of different neuronal cell types is critical for understanding their contribution to brain functions. Yet, automated and reliable classification of neurons remains a challenge, primarily because of their biological complexity. Typical approaches include laborious and expensive immunohistochemical analysis while feature extraction algorithms based on cellular characteristics have recently been proposed. The former rely on molecular markers, which are often expressed in many cell types, while the latter suffer from similar issues: finding features that are distinctive for each class has proven to be equally challenging. Moreover, both approaches are time consuming and demand a lot of human intervention. In this work we establish the first, automated cell-type classification method that relies on neuronal activity rather than molecular or cellular features. We test our method on a real-world dataset comprising of raw calcium activity signals for four neuronal types. We compare the performance of three different deep learning models and demonstrate that our method can achieve automated classification of neuronal cell types with unprecedented accuracy.
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- 2019
- Full Text
- View/download PDF
56. Progressive Decrease of Mitochondrial Motility during Maturation of Cortical Axons In Vitro and In Vivo
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Attila Losonczy, Tommy L. Lewis, Franck Polleux, Gergely F. Turi, and Seok-Kyu Kwon
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0301 basic medicine ,Aging ,Molecular neurobiology ,Motility ,Molecular neuroscience ,Oxidative phosphorylation ,Mitochondrion ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,Lipid biosynthesis ,medicine ,Animals ,Axon ,Cell organelles ,Mitochondrial transport ,Neurotrophic functions ,Compartmentalization (psychology) ,Axons ,Mitochondria ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,General Agricultural and Biological Sciences - Abstract
Summary The importance of mitochondria for neuronal function is evident by the large number of neurodegenerative diseases that have been associated with a disruption of mitochondrial function or transport (reviewed in [1, 2]). Mitochondria are essential for proper biological function as a result of their ability to produce ATP through oxidative phosphorylation, buffer cytoplasmic calcium, regulate lipid biosynthesis, and trigger apoptosis (reviewed in [2]). Efficient transport of mitochondria is thought to be particularly important in neurons in light of their compartmentalization, length of axonal processes, and high-energy requirements (reviewed in [3]). However, the majority of these results were obtained using short-term, in vitro neuronal culture models, and very little is currently known about mitochondrial dynamics in mature axons of the mammalian CNS in vitro or in vivo. Furthermore, recent evidence has demonstrated that mitochondrial immobilization at specific points along the axon, such as presynaptic boutons, play critical roles in axon morphogenesis [4, 5]. We report that as cortical axons mature, motility of mitochondria (but not other cargoes) is dramatically reduced and this coincides with increased localization to presynaptic sites. We also demonstrate using photo-conversion that in vitro mature axons display surprisingly limited long-range mitochondrial transport. Finally, using in vivo two-photon microscopy in anesthetized or awake-behaving mice, we document for the first time that mitochondrial motility is also remarkably low in distal cortical axons in vivo. These results argue that mitochondrial immobilization and presynaptic localization are important hallmarks of mature CNS axons both in vitro and in vivo.
- Published
- 2016
57. Distinct Contribution of Adult-Born Hippocampal Granule Cells to Context Encoding
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Alexander R. Goldberg, Joseph Tsai, Matthew Lovett-Barron, Patrick Kaifosh, Jeffrey D. Zaremba, Mazen A. Kheirbek, Liam Drew, Nathan Danielson, Attila Losonczy, René Hen, Christine A. Denny, and Elizabeth M. Balough
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0301 basic medicine ,Neurogenesis ,Cellular differentiation ,Optogenetics ,Biology ,Hippocampal formation ,Hippocampus ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Calcium imaging ,Animals ,Gene silencing ,Neurons ,Communication ,business.industry ,General Neuroscience ,Dentate gyrus ,Granule (cell biology) ,Cell Differentiation ,Microscopy, Fluorescence, Multiphoton ,030104 developmental biology ,Dentate Gyrus ,Calcium ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Adult-born granule cells (abGCs) have been implicated in cognition and mood; however, it remains unknown how these cells behave in vivo. Here, we have used two-photon calcium imaging to monitor the activity of young abGCs in awake behaving mice. We find that young adult-born neurons fire at a higher rate in vivo but paradoxically exhibit less spatial tuning than their mature counterparts. When presented with different contexts, mature granule cells underwent robust remapping of their spatial representations, and the few spatially tuned adult-born cells remapped to a similar degree. We next used optogenetic silencing to confirm the direct involvement of abGCs in context encoding and discrimination, consistent with their proposed role in pattern separation. These results provide the first in vivo characterization of abGCs and reveal their participation in the encoding of novel information.
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- 2016
58. Two-photon sensitive photolabile protecting groups: From molecular engineering to nanostructuration
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Boris V. Zemelman, Frédéric Bolze, Attila Losonczy, Alexandre Specht, and Sebastien Piant
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Indole test ,010405 organic chemistry ,Chemistry ,Electron donor ,General Chemistry ,Conjugated system ,010402 general chemistry ,Condensed Matter Physics ,Photochemistry ,01 natural sciences ,Two-photon absorption ,Acceptor ,Pentaerythritol ,0104 chemical sciences ,Molecular engineering ,chemistry.chemical_compound ,General Materials Science ,Protecting group - Abstract
General molecular engineering rules for the optimization of two-photon sensitive cages are presented and examples for nitrobenzyl, indole and nitrophenethyl platforms are highlighted. The efficiency of electron donor and acceptor groups in dipolar structures and the length of the conjugated system in the photolabile protecting group on two-photon uncaging efficiency will be discussed, as well as the emergence of symmetrical platform based on bis-electron donor or on quadrupolar architectures. We will then present our first results on the nano-structuration of donor-acceptor systems based on nitrophenetyl platform using diethyleneglycol or pentaerythritol cores.
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- 2016
59. Hippocampal Network Reorganization Underlies the Formation of a Temporal Association Memory
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James B. Priestley, Stefano Fusi, Ana Sofia Solis Canales, Luca Mazzucato, Elizabeth M. Balough, Erin Lavoie, Attila Losonczy, Angel Castro, Fabio Stefanini, and Mohsin Ahmed
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0301 basic medicine ,education.field_of_study ,Working memory ,General Neuroscience ,Population ,Hippocampus ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Fear conditioning ,Aversive Stimulus ,Association (psychology) ,education ,Psychology ,Neural coding ,Episodic memory ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Episodic memory requires linking events in time, a function dependent on the hippocampus. In "trace" fear conditioning, animals learn to associate a neutral cue with an aversive stimulus despite their separation in time by a delay period on the order of tens of seconds. But how this temporal association forms remains unclear. Here we use two-photon calcium imaging of neural population dynamics throughout the course of learning and show that, in contrast to previous theories, hippocampal CA1 does not generate persistent activity to bridge the delay. Instead, learning is concomitant with broad changes in the active neural population. Although neural responses were stochastic in time, cue identity could be read out from population activity over longer timescales after learning. These results question the ubiquity of seconds-long neural sequences during temporal association learning and suggest that trace fear conditioning relies on mechanisms that differ from persistent activity accounts of working memory.
- Published
- 2020
60. Volumetric Ca
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Siegfried, Weisenburger, Frank, Tejera, Jeffrey, Demas, Brandon, Chen, Jason, Manley, Fraser T, Sparks, Francisca, Martínez Traub, Tanya, Daigle, Hongkui, Zeng, Attila, Losonczy, and Alipasha, Vaziri
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Male ,Neurons ,Microscopy ,Brain ,Neuroimaging ,Hippocampus ,Article ,Molecular Imaging ,Mice, Inbred C57BL ,Mice ,Animals ,Calcium ,Female ,Single-Cell Analysis - Abstract
Calcium imaging using two-photon scanning microscopy has become an essential tool in neuroscience. However, in its typical implementation, the tradeoffs between fields of view, acquisition speeds, and depth restrictions in scattering brain tissue pose severe limitations. Here, using an integrated systems-wide optimization approach combined with multiple technical innovations, we introduce a new design paradigm for optical microscopy based on maximizing biological information while maintaining the fidelity of obtained neuron signals. Our modular design utilizes hybrid multi-photon acquisition and allows volumetric recording of neuroactivity at single-cell resolution within up to 1 × 1 × 1.22 mm volumes at up to 17 Hz in awake behaving mice. We establish the capabilities and potential of the different configurations of our imaging system at depth and across brain regions by applying it to in vivo recording of up to 12,000 neurons in mouse auditory cortex, posterior parietal cortex, and hippocampus.
- Published
- 2018
61. Vasoactive Intestinal Polypeptide-Expressing Interneurons in the Hippocampus Support Goal-Oriented Spatial Learning
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Boris V. Zemelman, James B. Priestley, Max Ladow, Andres Grosmark, Justin K. O’Hare, Wen-Ke Li, Gergely F. Turi, Spyridon Chavlis, Ioanna Pandi, Panayiota Poirazi, Jeff Fang Zhang, Zhenrui Liao, and Attila Losonczy
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0301 basic medicine ,Vasoactive intestinal peptide ,Population ,Place cell ,Spatial Learning ,Hippocampus ,Neocortex ,Biology ,Hippocampal formation ,Optogenetics ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Interneurons ,medicine ,Animals ,education ,CA1 Region, Hippocampal ,education.field_of_study ,Appetitive Behavior ,General Neuroscience ,Pyramidal Cells ,Neural Inhibition ,030104 developmental biology ,medicine.anatomical_structure ,Pyramidal cell ,Neuroscience ,Goals ,030217 neurology & neurosurgery ,Vasoactive Intestinal Peptide - Abstract
Summary Diverse computations in the neocortex are aided by specialized GABAergic interneurons (INs), which selectively target other INs. However, much less is known about how these canonical disinhibitory circuit motifs contribute to network operations supporting spatial navigation and learning in the hippocampus. Using chronic two-photon calcium imaging in mice performing random foraging or goal-oriented learning tasks, we found that vasoactive intestinal polypeptide-expressing (VIP+), disinhibitory INs in hippocampal area CA1 form functional subpopulations defined by their modulation by behavioral states and task demands. Optogenetic manipulations of VIP+ INs and computational modeling further showed that VIP+ disinhibition is necessary for goal-directed learning and related reorganization of hippocampal pyramidal cell population dynamics. Our results demonstrate that disinhibitory circuits in the hippocampus play an active role in supporting spatial learning. Video Abstract
- Published
- 2018
62. Ambient GABA modulates septo-hippocampal inhibitory terminals via presynaptic GABAb receptors
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Gábor Wittmann, Gergely F. Turi, Attila Losonczy, and Ronald M. Lechan
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Male ,Mice, 129 Strain ,Patch-Clamp Techniques ,Presynaptic Terminals ,Mice, Transgenic ,Hippocampal formation ,Biology ,GABAB receptor ,Inhibitory postsynaptic potential ,Hippocampus ,Tissue Culture Techniques ,Cellular and Molecular Neuroscience ,Interneurons ,Negative feedback ,Neural Pathways ,Animals ,Gene Knock-In Techniques ,Patch clamp ,Receptor ,gamma-Aminobutyric Acid ,Pharmacology ,Neural Inhibition ,Network activity ,Mice, Inbred C57BL ,Receptors, GABA-B ,nervous system ,GABAergic ,Female ,Septum of Brain ,Neuroscience - Abstract
The septo-hippocampal GABAergic pathway connects inhibitory neurons in the medial septum with hippocampal interneurons. Phasic release of GABA from septo-hippocampal terminals is thought to play an important role in shaping hippocampal network activity during behavior. Here, we found that GABA release from septo-hippocampal terminals is under negative feedback from the hippocampal local inhibitory network. We found that the strength of septo-hippocampal GABAergic inhibition is constrained by presynaptic GABAb receptors that are activated by ambient GABA during states of increased hippocampal network activity.
- Published
- 2015
63. CA1 pyramidal cell diversity enabling parallel information processing in the hippocampus
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Ivan Soltesz and Attila Losonczy
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0301 basic medicine ,Electronic Data Processing ,General Neuroscience ,Ca1 pyramidal neuron ,Dentate gyrus ,Pyramidal Cells ,Information processing ,Hippocampus ,Hippocampal formation ,Biology ,Spatial memory ,Article ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,nervous system ,Homogeneous ,Cellular neuroscience ,Neural Pathways ,Animals ,Humans ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Hippocampal network operations supporting spatial navigation and declarative memory are traditionally interpreted in a framework where each hippocampal area, such as the dentate gyrus, CA3, and CA1, consists of homogeneous populations of functionally equivalent principal neurons. However, heterogeneity within hippocampal principal cell populations, in particular within pyramidal cells at the main CA1 output node, is increasingly recognized and includes developmental, molecular, anatomical, and functional differences. Here we review recent progress in the delineation of hippocampal principal cell subpopulations by focusing on radially defined subpopulations of CA1 pyramidal cells, and we consider how functional segregation of information streams, in parallel channels with nonuniform properties, could represent a general organizational principle of the hippocampus supporting diverse behaviors.
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- 2017
64. Behavioral consequences of GABAergic neuronal diversity
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Attila Losonczy and Matthew Lovett-Barron
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Cerebral Cortex ,Behavior ,education.field_of_study ,Neocortex ,General Neuroscience ,media_common.quotation_subject ,Population ,Hippocampus ,Biology ,Inhibitory postsynaptic potential ,Inhibitory cell ,medicine.anatomical_structure ,nervous system ,medicine ,Animals ,Humans ,GABAergic ,Local circuit ,GABAergic Neurons ,Nerve Net ,education ,Neuroscience ,Diversity (politics) ,media_common - Abstract
The majority of cellular diversity in the hippocampus and neocortex derives from a relatively small population of local inhibitory interneurons. Recent technological advances have facilitated the recording and manipulation of defined inhibitory cell classes in awake rodents, revealing new and surprising roles for these cells in local circuit function and behavior. Here we review recent progress in the analysis of inhibitory interneuron subtypes in neocortex and hippocampus during behavior, and suggest opportunities and considerations for extending this research program.
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- 2014
65. Dendritic Inhibition in the Hippocampus Supports Fear Learning
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Attila Losonczy, Mazen A. Kheirbek, René Hen, Thomas Reardon, Patrick Kaifosh, Nathan Danielson, Gergely F. Turi, Jeffrey D. Zaremba, Matthew Lovett-Barron, and Boris V. Zemelman
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1.2 Psychological and socioeconomic processes ,General Science & Technology ,1.1 Normal biological development and functioning ,Population ,Glycine ,Hippocampus ,Context (language use) ,Sensory system ,Receptors, Nicotinic ,Hippocampal formation ,Nicotinic ,Basic Behavioral and Social Science ,Article ,Mice ,Receptors, Glycine ,Underpinning research ,Interneurons ,Receptors ,Behavioral and Social Science ,Conditioning, Psychological ,medicine ,Hippocampal ,Animals ,Learning ,education ,CA1 Region, Hippocampal ,education.field_of_study ,Multidisciplinary ,Neurosciences ,CA1 Region ,Neural Inhibition ,Dendrites ,Fear ,Amygdala ,Entorhinal cortex ,Mental Health ,medicine.anatomical_structure ,nervous system ,Neurological ,Psychological ,Aversive Stimulus ,Pyramidal cell ,Somatostatin ,Psychology ,Neuroscience ,Conditioning - Abstract
Fear, Memory, and Place Contextual fear conditioning (CFC) is widely used as a hippocampal-dependent classical conditioning task to model human episodic memory. Lovett-Barron et al. (p. 857 ) combined in vivo imaging with pharmacology, pharmacogenetics, and optogenetics and they found that somatostatin-expressing, dendrite-targeting γ-aminobutyric acid–releasing interneurons in hippocampal area CA1 are required for CFC. During CFC, sensory features of the aversive event reach hippocampal output neurons through excitatory cortical afferents and require active inhibitory filtering to ensure that the hippocampus exclusively encodes the conditioned stimulus.
- Published
- 2014
66. Volumetric Ca2+ Imaging in the Mouse Brain Using Hybrid Multiplexed Sculpted Light Microscopy
- Author
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Siegfried Weisenburger, Fraser T. Sparks, Tanya L. Daigle, Jason Manley, Francisca Martínez Traub, Alipasha Vaziri, Brandon Chen, Frank Tejera, Hongkui Zeng, Attila Losonczy, and Jeff Demas
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Systems neuroscience ,0303 health sciences ,business.industry ,Posterior parietal cortex ,Hippocampus ,Biology ,Modular design ,Auditory cortex ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Calcium imaging ,Microscopy ,medicine ,Neuron ,business ,030217 neurology & neurosurgery ,030304 developmental biology ,Biomedical engineering - Abstract
Calcium imaging using two-photon scanning microscopy has become an essential tool in neuroscience. However, in its typical implementation, the tradeoffs between fields of view, acquisition speeds, and depth restrictions in scattering brain tissue pose severe limitations. Here, using an integrated systems-wide optimization approach combined with multiple technical innovations, we introduce a new design paradigm for optical microscopy based on maximizing biological information while maintaining the fidelity of obtained neuron signals. Our modular design utilizes hybrid multi-photon acquisition and allows volumetric recording of neuroactivity at single-cell resolution within up to 1 × 1 × 1.22 mm volumes at up to 17 Hz in awake behaving mice. We establish the capabilities and potential of the different configurations of our imaging system at depth and across brain regions by applying it to in vivo recording of up to 12,000 neurons in mouse auditory cortex, posterior parietal cortex, and hippocampus.
- Published
- 2019
67. Sublayer-specific coding dynamics during spatial navigation and learning in hippocampal area CA1
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Jeffrey D. Zaremba, Nathan Danielson, Max Ladow, Patrick Kaifosh, John C. Bowler, and Attila Losonczy
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0301 basic medicine ,Male ,Computer science ,Hippocampus ,Action Potentials ,Hippocampal formation ,ENCODE ,Spatial memory ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Reward ,Animals ,Learning ,Episodic memory ,Spatial analysis ,CA1 Region, Hippocampal ,Communication ,business.industry ,General Neuroscience ,Pyramidal Cells ,Representation (systemics) ,Electrophysiology ,030104 developmental biology ,nervous system ,Female ,business ,Neuroscience ,030217 neurology & neurosurgery ,Spatial Navigation - Abstract
The mammalian hippocampus is critical for spatial information processing and episodic memory. Its primary output cells, CA1 pyramidal cells (CA1 PCs), vary in genetics, morphology, connectivity, and electrophysiological properties. It is therefore possible that distinct CA1 PC subpopulations encode different features of the environment and differentially contribute to learning. To test this hypothesis, we optically monitored activity in deep and superficial CA1 PCs segregated along the radial axis of the mouse hippocampus and assessed the relationship between sublayer dynamics and learning. Superficial place maps were more stable than deep during head-fixed exploration. Deep maps, however, were preferentially stabilized during goal-oriented learning, and representation of the reward zone by deep cells predicted task performance. These findings demonstrate that superficial CA1 PCs provide a more stable map of an environment, while their counterparts in the deep sublayer provide a more flexible representation that is shaped by learning about salient features in the environment. VIDEO ABSTRACT.
- Published
- 2016
68. Erratum for the Research Article 'Gating of hippocampal activity, plasticity, and memory by entorhinal cortex long-range inhibition' by J. Basu, J. D. Zaremba, S. K. Cheung, F. L. Hitti, B. V. Zemelman, A. Losonczy, S. A. Siegelbaum
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Boris V. Zemelman, Attila Losonczy, Jayeeta Basu, Steven A. Siegelbaum, Stephanie Cheung, Jeffrey D. Zaremba, and Frederick L. Hitti
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0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Multidisciplinary ,Range (biology) ,Gating ,Biology ,Hippocampal formation ,Plasticity ,Entorhinal cortex ,Neuroscience ,030217 neurology & neurosurgery - Published
- 2016
69. Rabies virus CVS-N2cΔG strain enhances retrograde synaptic transfer and neuronal viability
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Katherine R. Croce, Christoph Wirblich, Matthias J. Schnell, Thomas Reardon, Attila Losonczy, Thomas M. Jessell, Gergely F. Turi, and Andrew J. Murray
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0301 basic medicine ,Nerve net ,Neuroscience(all) ,Transgene ,Action Potentials ,Mice, Transgenic ,Optogenetics ,Biology ,medicine.disease_cause ,Article ,03 medical and health sciences ,Mice ,Neuroblastoma ,0302 clinical medicine ,Viral Envelope Proteins ,Neural Pathways ,medicine ,Premovement neuronal activity ,Animals ,Humans ,Cells, Cultured ,Glycoproteins ,Neurons ,Strain (chemistry) ,General Neuroscience ,Rabies virus ,Electric Stimulation ,Complementation ,Mice, Inbred C57BL ,Luminescent Proteins ,Protein Transport ,030104 developmental biology ,medicine.anatomical_structure ,Helper virus ,Nerve Net ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Virally-based transsynaptic tracing technologies are powerful experimental tools for neuronal circuit mapping. The glycoprotein-deletion variant of the SAD-B19 vaccine strain rabies virus (RABV) has been the reagent of choice in monosynaptic tracing, since it permits the mapping of synaptic inputs to genetically marked neurons. Since its introduction, new helper viruses and reagents that facilitate complementation have enhanced the efficiency of SAD-B19ΔG transsynaptic transfer, but there has been little focus on improvements to the core RABV strain. Here we generate a new deletion-mutant strain, CVS-N2cΔG, and examine its neuronal toxicity and efficiency in directing retrograde transsynaptic transfer. We find that by comparison with SAD-B19ΔG, the CVS-N2cΔG strain exhibits a reduction in neuronal toxicity and a marked enhancement in transsynaptic neuronal transfer. We conclude that the CVS-N2cΔG strain provides a more effective means of mapping neuronal circuitry and of monitoring and manipulating neuronal activity in vivo in the mammalian central nervous system.
- Published
- 2016
70. Gating of hippocampal activity, plasticity, and memory by entorhinal cortex long-range inhibition
- Author
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Boris V. Zemelman, Jeffrey D. Zaremba, Stephanie Cheung, Frederick L. Hitti, Attila Losonczy, Jayeeta Basu, and Steven A. Siegelbaum
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0301 basic medicine ,Memory, Long-Term ,Heterosynaptic plasticity ,Gating ,Hippocampal formation ,Inhibitory postsynaptic potential ,gamma-Aminobutyric acid ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Neuroplasticity ,medicine ,Animals ,Entorhinal Cortex ,GABAergic Neurons ,CA1 Region, Hippocampal ,Evoked Potentials ,gamma-Aminobutyric Acid ,Neuronal Plasticity ,Multidisciplinary ,Chemistry ,Pyramidal Cells ,Dendrites ,Entorhinal cortex ,CA3 Region, Hippocampal ,030104 developmental biology ,Inhibitory Postsynaptic Potentials ,nervous system ,Synapses ,Excitatory postsynaptic potential ,Neuroscience ,030217 neurology & neurosurgery ,medicine.drug - Abstract
The cortico-hippocampal circuit is critical for storage of associational memories. Most studies have focused on the role in memory storage of the excitatory projections from entorhinal cortex to hippocampus. However, entorhinal cortex also sends inhibitory projections, whose role in memory storage and cortico-hippocampal activity remains largely unexplored. We found that these long-range inhibitory projections enhance the specificity of contextual and object memory encoding. At the circuit level, these γ-aminobutyric acid (GABA)-releasing projections target hippocampal inhibitory neurons and thus act as a disinhibitory gate that transiently promotes the excitation of hippocampal CA1 pyramidal neurons by suppressing feedforward inhibition. This enhances the ability of CA1 pyramidal neurons to fire synaptically evoked dendritic spikes and to generate a temporally precise form of heterosynaptic plasticity. Long-range inhibition from entorhinal cortex may thus increase the precision of hippocampal-based long-term memory associations by assessing the salience of mnemonormation to the immediate sensory input.
- Published
- 2016
71. Regulation of neuronal input transformations by tunable dendritic inhibition
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Scott M. Sternson, Patrick Kaifosh, Attila Losonczy, Jean François Nicoud, Peter Lee, Frédéric Bolze, Xiao Hua Sun, Matthew Lovett-Barron, Gergely F. Turi, and Boris V. Zemelman
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Patch-Clamp Techniques ,Models, Neurological ,Biophysics ,Regulator ,Glutamic Acid ,Hippocampus ,Channelrhodopsin ,Mice, Transgenic ,Gating ,In Vitro Techniques ,Neurotransmission ,Biology ,Hippocampal formation ,Inhibitory postsynaptic potential ,Synaptic Transmission ,Membrane Potentials ,GABA Antagonists ,Mice ,Receptors, Glycine ,Channelrhodopsins ,Interneurons ,Transduction, Genetic ,medicine ,Animals ,RNA, Small Interfering ,gamma-Aminobutyric Acid ,Cerebral Cortex ,Glutamate Decarboxylase ,Pyramidal Cells ,General Neuroscience ,Neural Inhibition ,Valine ,Dependovirus ,Ligand-Gated Ion Channels ,Electric Stimulation ,DNA-Binding Proteins ,Mice, Inbred C57BL ,Pyridazines ,Luminescent Proteins ,Parvalbumins ,medicine.anatomical_structure ,nervous system ,Mutation ,Synapses ,Pyramidal cell ,Excitatory Amino Acid Antagonists ,Neuroscience ,Photic Stimulation ,Transcription Factors - Abstract
Transforming synaptic input into action potential output is a fundamental function of neurons. The pattern of action potential output from principal cells of the mammalian hippocampus encodes spatial and nonspatial information, but the cellular and circuit mechanisms by which neurons transform their synaptic input into a given output are unknown. Using a combination of optical activation and cell type-specific pharmacogenetic silencing in vitro, we found that dendritic inhibition is the primary regulator of input-output transformations in mouse hippocampal CA1 pyramidal cells, and acts by gating the dendritic electrogenesis driving burst spiking. Dendrite-targeting interneurons are themselves modulated by interneurons targeting pyramidal cell somata, providing a synaptic substrate for tuning pyramidal cell output through interactions in the local inhibitory network. These results provide evidence for a division of labor in cortical circuits, where distinct computational functions are implemented by subtypes of local inhibitory neurons.
- Published
- 2012
72. Network mechanisms of theta related neuronal activity in hippocampal CA1 pyramidal neurons
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Jeffrey C. Magee, Boris V. Zemelman, Attila Losonczy, and Alipasha Vaziri
- Subjects
Patch-Clamp Techniques ,Nerve net ,Pyramidal Cells ,General Neuroscience ,Place cell ,Hippocampus ,Stimulation ,Hippocampal formation ,Biology ,Inhibitory postsynaptic potential ,Article ,Mice, Inbred C57BL ,Mice ,Organ Culture Techniques ,medicine.anatomical_structure ,Inhibitory Postsynaptic Potentials ,medicine ,Animals ,Premovement neuronal activity ,Gene Knock-In Techniques ,Nerve Net ,Theta Rhythm ,Neuroscience ,Shunting inhibition - Abstract
Although hippocampal theta oscillations represent a prime example of temporal coding in the mammalian brain, little is known about the specific biophysical mechanisms. Intracellular recordings implicate a particular abstract oscillatory interference model of hippocampal theta activity; the soma-dendrite interference model. To gain insight into the cellular and circuit level mechanisms of theta activity we implemented a similar form of interference using the actual hippocampal network in mice in vitro. We found that pairing increasing levels of phasic dendritic excitation with phasic stimulation of perisomatic projecting inhibitory interneurons induced a somatic polarization and action potential timing profile that reproduced most common features. Alterations in the temporal profile of inhibition were required to fully capture all features. These data suggest that theta-related place cell activity is generated through an interaction between a phasic dendritic excitation and a phasic perisomatic shunting inhibition delivered by interneurons; a subset of which undergo activity-dependent presynaptic modulation.
- Published
- 2010
73. O18. Changes in Effective Hippocampal Network Coupling Mediate Learning and Memory of Associations Between Temporally Discontiguous Stimuli
- Author
-
Angel Castro, Luca Mazzucato, Stefano Fusi, Elizabeth M. Balough, Attila Losonczy, Erin Lavoie, Mohsin Ahmed, James B. Priestley, and Fabio Stefanini
- Subjects
Physics ,Coupling (electronics) ,Hippocampal formation ,Neuroscience ,Biological Psychiatry - Published
- 2018
74. Fast Synaptic Subcortical Control of Hippocampal Circuits
- Author
-
Zsolt Borhegyi, Attila Losonczy, Gábor Nyiri, Andor Domonkos, Boris V. Zemelman, Noemi Holderith, Jeffrey C. Magee, Balázs Hangya, Tamás F. Freund, and Viktor Sebestyén Varga
- Subjects
Serotonin ,Patch-Clamp Techniques ,Interneuron ,Central nervous system ,Glutamic Acid ,Hippocampus ,Neurotransmission ,Hippocampal formation ,Biology ,Serotonergic ,Rats, Sprague-Dawley ,Mice ,Interneurons ,Neural Pathways ,medicine ,Animals ,Neurons, Afferent ,Multidisciplinary ,Excitatory Postsynaptic Potentials ,Neural Inhibition ,Anatomy ,Synaptic Potentials ,Electric Stimulation ,Rats ,medicine.anatomical_structure ,Metabotropic receptor ,Inhibitory Postsynaptic Potentials ,Synapses ,Excitatory postsynaptic potential ,Raphe Nuclei ,Neuroscience ,Photic Stimulation - Abstract
Subcortical Network Regulation Subcortical neuromodulatory centers dominate the motivational and emotional state–dependent control of cortical functions. Control of cortical circuits has been thought to involve a slow, diffuse neuromodulation that affects the excitability of large numbers of neurons relatively indiscriminately. Varga et al. (p. 449 ) describe a form of subcortical control of cortical information processing whereby strong, spatiotemporally precise excitatory input from midbrain serotonergic neurons produces a robust activation of hippocampal interneurons. This effect is mediated by a synaptic release of both serotonin and glutamate and impacts network activity patterns.
- Published
- 2009
75. Associative pairing enhances action potential back-propagation in radial oblique branches of CA1 pyramidal neurons
- Author
-
Daniel Johnston, Jeffrey C. Magee, Sonia Gasparini, Xixi Chen, and Attila Losonczy
- Subjects
Amplitude ,Action potential ,Physiology ,Chemistry ,Synaptic plasticity ,Biophysics ,Channel blocker ,Depolarization ,Hippocampal formation ,Neuroscience ,Signal ,Ion channel - Abstract
Back-propagating action potentials (bAPs) are involved in associative synaptic plasticity and the modulation of dendritic excitability. We have used high-speed confocal and two-photon imaging to measure calcium and voltage signals associated with action potential propagation into oblique branches of CA1 pyramidal neurons in adult hippocampal slices. The spatial profile of the bAP-associated Ca2+ influx was biphasic, with an initial increase in the proximity of the branch point followed by a progressive decrease. Voltage imaging in the branches showed that bAP amplitude was initially constant and then steadily declined with distance from the soma. To determine the role of transient K+ channels in this profile, we used external Ba2+ (150 μm) as a channel blocker, after characterizing its effect on A-type K+ channels in the apical trunk. Bath application of Ba2+ significantly reduced the A-type K+ current in outside-out patches and nearly eliminated the distance-dependent decrease in bAP amplitude and its associated Ca2+ signal. Finally, small amplitude bAPs at more distal oblique branch locations could be boosted by simultaneous branch depolarization, such that the paired Ca2+ signal became nearly the same for proximal and distal oblique dendrites. These data suggest that dendritic K+ channels regulate the amplitude of bAPs to create a dendritic Ca2+ signal whose magnitude is inversely related to the electrotonic distance from the soma when bAPs are not associated with a significant amount of localized synaptic input. This distance-dependent Ca2+ signal from bAPs, however, can be amplified and a strong associative signal is produced once the proper correlation between synaptic activation and AP output is achieved. We hypothesize that these two signals may be involved in the regulation of the expression and activity of dendritic voltage- and ligand-gated ion channels.
- Published
- 2007
76. Circuits supporting the grid
- Author
-
Attila Losonczy and Matthew Lovett-Barron
- Subjects
Quantitative Biology::Neurons and Cognition ,Nerve net ,Computer science ,General Neuroscience ,Neural Inhibition ,Hippocampus ,Hippocampal formation ,Inhibitory postsynaptic potential ,Grid ,Entorhinal cortex ,medicine.anatomical_structure ,Excitatory postsynaptic potential ,medicine ,Neuroscience - Abstract
Two studies show that local inhibitory connectivity and hippocampal excitatory input support the spatial firing patterns of entorhinal grid cells, providing support for continuous attractor model of grid cell firing.
- Published
- 2013
77. Cell type dependence and variability in the short‐term plasticity of EPSCs in identified mouse hippocampal interneurones
- Author
-
Peter Somogyi, Attila Losonczy, Ryuichi Shigemoto, Zoltan Nusser, and Li-Mei Zhang
- Subjects
Male ,Cell type ,Patch-Clamp Techniques ,Physiology ,Postsynaptic Current ,In Vitro Techniques ,Neurotransmission ,Hippocampal formation ,Biology ,Receptors, Metabotropic Glutamate ,Hippocampus ,Models, Biological ,Membrane Potentials ,Mice ,Interneurons ,Postsynaptic potential ,medicine ,Animals ,Axon ,Neuronal Plasticity ,musculoskeletal, neural, and ocular physiology ,Calcium-Binding Proteins ,Neuropeptides ,Subiculum ,Excitatory Postsynaptic Potentials ,Dendrites ,Original Articles ,Axons ,Mice, Inbred C57BL ,medicine.anatomical_structure ,nervous system ,Excitatory postsynaptic potential ,Nerve Net ,Neuroscience - Abstract
Synapses exhibit different short-term plasticity patterns and this behaviour influences information processing in neuronal networks. We tested how the short-term plasticity of excitatory postsynaptic currents (EPSCs) depends on the postsynaptic cell type, identified by axonal arborizations and molecular markers in the hippocampal CA1 area. Three distinct types of short-term synaptic behaviour (facilitating, depressing and combined facilitating-depressing) were defined by fitting a dynamic neurotransmission model to the data. Approximately 75 % of the oriens-lacunosum-moleculare (O-LM) interneurones received facilitating EPSCs, but in three of 12 O-LM cells EPSCs also showed significant depression. Over 90 % of the O-LM cells were immunopositive for somatostatin and mGluR1alpha and all tested cells were decorated by strongly mGluR7a positive axon terminals. Responses in eight of 12 basket cells were described well with a model involving only depression, but the other cells displayed combined facilitating-depressing EPSCs. No apparent difference was found between the plasticity of EPSCs in cholecystokinin- or parvalbumin-containing basket cells. In oriens-bistratified cells (O-Bi), two of nine cells showed facilitating EPSCs, another two depressing, and the remaining five cells combined facilitating-depressing EPSCs. Seven of 10 cells tested for somatostatin were immunopositive, but mGluR1alpha was detectable only in two of 11 tested cells. Furthermore, most O-Bi cells projected to the CA3 area and the subiculum, as well as outside the hippocampal formation. Postsynaptic responses to action potentials recorded in vivo from a CA1 place cell were modelled, and revealed great differences between and within cell types. Our results demonstrate that the short-term plasticity of EPSCs is cell type dependent, but with significant heterogeneity within all three interneurone populations.
- Published
- 2002
78. In Vivo Imaging of Dentate Gyrus Mossy Cells in Behaving Mice
- Author
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Gergely F. Turi, Spyridon Chavlis, Nathan Danielson, Panayiota Poirazi, Panagiotis C. Petrantonakis, Max Ladow, and Attila Losonczy
- Subjects
Neurons ,0301 basic medicine ,Cell type ,Behavior, Animal ,General Neuroscience ,Dentate gyrus ,Biology ,Spatial memory ,Article ,Spatial coding ,Active participation ,Mice ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Dentate Gyrus ,Mossy Fibers, Hippocampal ,Excitatory postsynaptic potential ,Animals ,Calcium ,Neuroscience ,030217 neurology & neurosurgery ,Preclinical imaging ,Spatial Navigation - Abstract
Mossy cells in the hilus of the dentate gyrus constitute a major excitatory principal cell type in the mammalian hippocampus; however, it remains unknown how these cells behave in vivo. Here, we have used two-photon Ca2+ imaging to monitor the activity of mossy cells in awake, behaving mice. We find that mossy cells are significantly more active than dentate granule cells in vivo, exhibit spatial tuning during head-fixed spatial navigation, and undergo robust remapping of their spatial representations in response to contextual manipulation. Our results provide a functional characterization of mossy cells in the behaving animal and demonstrate their active participation in spatial coding and contextual representation.
- Published
- 2017
79. SIMA: Python software for analysis of dynamic fluorescence imaging data
- Author
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Attila Losonczy, Patrick Kaifosh, Nathan Danielson, and Jeffrey D. Zaremba
- Subjects
in vivo GECI imaging ,Fluorescence-lifetime imaging microscopy ,Source code ,Computer science ,media_common.quotation_subject ,Biomedical Engineering ,Neuroscience (miscellaneous) ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,lcsh:RC321-571 ,03 medical and health sciences ,0302 clinical medicine ,Documentation ,Software ,fluorescence imaging ,Computer graphics (images) ,Methods Article ,Segmentation ,motion correction ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,030304 developmental biology ,Graphical user interface ,media_common ,computer.programming_language ,multi-photon microscopy ,0303 health sciences ,business.industry ,Keywords: calcium imaging ,segmentation ,analysis software ,Python (programming language) ,Python language ,Data science ,Computer Science Applications ,python ,calcium imaging ,business ,computer ,030217 neurology & neurosurgery ,Preclinical imaging ,Neuroscience - Abstract
Fluorescence imaging is a powerful method for monitoring dynamic signals in the nervous system. However, analysis of dynamic fluorescence imaging data remains burdensome, in part due to the shortage of available software tools. To address this need, we have developed SIMA, an open source Python package that facilitates common analysis tasks related to fluorescence imaging. Functionality of this package includes correction of motion artifacts occurring during in vivo imaging with laser-scanning microscopy, segmentation of imaged fields into regions of interest (ROIs), and extraction of signals from the segmented ROIs. We have also developed a graphical user interface (GUI) for manual editing of the automatically segmented ROIs and automated registration of ROIs across multiple imaging datasets. This software has been designed with flexibility in mind to allow for future extension with different analysis methods and potential integration with other packages. Software, documentation, and source code for the SIMA package and ROI Buddy GUI are freely available at http://www.losonczylab.org/sima/.
- Published
- 2014
80. Parvalbumin-positive basket cells differentiate among hippocampal pyramidal cells
- Author
-
Nathan Danielson, Csaba Varga, Attila Losonczy, Marianne Bezaire, Ivan Soltesz, Ivan Marchionni, Sang-Hun Lee, and Matthew Lovett-Barron
- Subjects
Male ,Nerve net ,Neuroscience(all) ,Prefrontal Cortex ,Hippocampal formation ,Inhibitory postsynaptic potential ,Amygdala ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Physical Conditioning, Animal ,medicine ,Animals ,Entorhinal Cortex ,Prefrontal cortex ,CA1 Region, Hippocampal ,030304 developmental biology ,0303 health sciences ,biology ,General Neuroscience ,Pyramidal Cells ,Entorhinal cortex ,humanities ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Parvalbumins ,nervous system ,biology.protein ,Excitatory postsynaptic potential ,Calcium ,Female ,Nerve Net ,Neuroscience ,030217 neurology & neurosurgery ,Parvalbumin - Abstract
SummaryCA1 pyramidal cells (PCs) are not homogeneous but rather can be grouped by molecular, morphological, and functional properties. However, less is known about synaptic sources differentiating PCs. Using paired recordings in vitro, two-photon Ca2+ imaging in vivo, and computational modeling, we found that parvalbumin-expressing basket cells (PVBCs) evoked greater inhibition in CA1 PCs located in the deep compared to superficial layer of stratum pyramidale. In turn, analysis of reciprocal connectivity revealed more frequent excitatory inputs to PVBCs by superficial PCs, demonstrating bias in target selection by both the excitatory and inhibitory local connections in CA1. Additionally, PVBCs further segregated among deep PCs, preferentially innervating the amygdala-projecting PCs but receiving preferential excitation from the prefrontal cortex-projecting PCs, thus revealing distinct perisomatic inhibitory interactions between separate output channels. These results demonstrate the presence of heterogeneous PVBC-PC microcircuits, potentially contributing to the sparse and distributed structure of hippocampal network activity.Video Abstract
- Published
- 2014
81. Rapid activation of microglial cells by hypoxia, kainic acid, and potassium ions in slice preparations of the rat hippocampus
- Author
-
Attila Losonczy, Hajnalka Ábrahám, G. Czéh, and Gyula Lázár
- Subjects
Male ,medicine.medical_specialty ,Kainic acid ,Central nervous system ,Action Potentials ,Macrophage-1 Antigen ,Hippocampal formation ,Hippocampus ,Avian Proteins ,chemistry.chemical_compound ,Antigens, CD ,Antigens, Neoplasm ,Internal medicine ,Excitatory Amino Acid Agonists ,medicine ,Animals ,Gliosis ,Rats, Wistar ,Hypoxia, Brain ,Molecular Biology ,Cell Size ,Neurons ,Kainic Acid ,Membrane Glycoproteins ,biology ,Microglia ,Pyramidal Cells ,General Neuroscience ,Blood Proteins ,Hypoxia (medical) ,Immunohistochemistry ,Electric Stimulation ,Rats ,Endocrinology ,medicine.anatomical_structure ,nervous system ,Biochemistry ,Integrin alpha M ,chemistry ,Antigens, Surface ,Basigin ,Potassium ,biology.protein ,Neuroglia ,Neurology (clinical) ,medicine.symptom ,Immunostaining ,Developmental Biology - Abstract
Microglial activation induced by hypoxia, kainic acid and elevated potassium concentration, all of which alter neuronal function, was studied in hippocampal slices. The activation of microglia was detected by immunostaining with a monoclonal antibody (OX-42) raised against a type 3 complement receptor (CD11b). During activation the phenotype of microglia changes and the intensity of staining of individual cells increases. Oxygen deprivation depressed the focal responses of CA1 neurons to stratum radiatum volleys. Microglial activation was time dependent. Ten minute hypoxia caused mild activation, and after 20 min, a strong microglial reaction could be observed. Although neuronal function returned during reoxygenation, the morphological signs of microglial activation remained. Epileptiform activity of hippocampal neurons, followed by depression, was induced by application of 0.5 mM kainic acid, in a time and dose dependent manner. Washing out kainic acid did not alter microglial reaction. Elevated concentrations of potassium ions induced microglial changes similar to those induced by hypoxia and kainic acid. It is therefore suggested that an elevated extracellular potassium ion concentration may be the common factor in microglial activation observed in these experiments since this is raised both in hypoxia and under the effect of excitotoxins.
- Published
- 2001
82. Septo-hippocampal GABAergic signaling across multiple modalities in awake mice
- Author
-
Patrick Kaifosh, Gergely F. Turi, Attila Losonczy, Thomas Reardon, and Matthew Lovett-Barron
- Subjects
RNA, Untranslated ,Population ,Hippocampus ,Channelrhodopsin ,Action Potentials ,Sensory system ,Mice, Transgenic ,Tetrodotoxin ,Stimulus (physiology) ,Hippocampal formation ,Biology ,In Vitro Techniques ,Motor Activity ,Choline O-Acetyltransferase ,Mice ,Calmodulin ,Channelrhodopsins ,Postsynaptic potential ,Conditioning, Psychological ,Neural Pathways ,Animals ,Anesthetics, Local ,Wakefulness ,education ,gamma-Aminobutyric Acid ,education.field_of_study ,Glutamate Decarboxylase ,General Neuroscience ,fungi ,Proteins ,DNA-Binding Proteins ,Parvalbumins ,nervous system ,GABAergic ,Septum of Brain ,Plant Lectins ,Neuroscience ,Signal Transduction ,Transcription Factors - Abstract
Hippocampal interneurons receive GABAergic input from the medial septum. Using two-photon Ca(2+) imaging of axonal boutons in hippocampal CA1 of behaving mice, we found that populations of septo-hippocampal GABAergic boutons were activated during locomotion and salient sensory events; sensory responses scaled with stimulus intensity and were abolished by anesthesia. We found similar activity patterns among boutons with common putative postsynaptic targets, with low-dimensional bouton population dynamics being driven primarily by presynaptic spiking.
- Published
- 2013
83. Control of timing, rate and bursts of hippocampal place cells by dendritic and somatic inhibition
- Author
-
Frances S. Chance, Boris V. Zemelman, Jeffrey C. Magee, Jinhyun Kim, Sébastien Royer, Attila Losonczy, and György Buzsáki
- Subjects
Optics and Photonics ,Patch-Clamp Techniques ,Time Factors ,Interneuron ,Light ,Movement ,Green Fluorescent Proteins ,Biophysics ,Action Potentials ,Mice, Transgenic ,Biology ,Hippocampal formation ,Optogenetics ,Inhibitory postsynaptic potential ,Hippocampus ,Article ,Bursting ,Mice ,medicine ,Gene silencing ,Animals ,Humans ,Patch clamp ,Probability ,Neurons ,Behavior, Animal ,General Neuroscience ,musculoskeletal, neural, and ocular physiology ,Spectrum Analysis ,Neural Inhibition ,Dendrites ,Electric Stimulation ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Parvalbumins ,nervous system ,Touch ,Time Perception ,biology.protein ,Exercise Test ,Halorhodopsins ,Somatostatin ,Neuroscience ,Parvalbumin ,Photic Stimulation - Abstract
A consortium of inhibitory neurons control the firing patterns of pyramidal cells, but their specific roles in the behaving animal are largely unknown. We performed simultaneous physiological recordings and optogenetic silencing of either perisomatic (parvalbumin (PV) expressing) or dendrite-targeting (somatostatin (SOM) expressing) interneurons in hippocampal area CA1 of head-fixed mice actively moving a treadmill belt rich with visual-tactile stimuli. Silencing of either PV or SOM interneurons increased the firing rates of pyramidal cells selectively in their place fields, with PV and SOM interneurons having their largest effect during the rising and decaying parts of the place field, respectively. SOM interneuron silencing powerfully increased burst firing without altering the theta phase of spikes. In contrast, PV interneuron silencing had no effect on burst firing, but instead shifted the spikes’ theta phase toward the trough of theta. These findings indicate that perisomatic and dendritic inhibition have distinct roles in controlling the rate, burst and timing of hippocampal pyramidal cells.
- Published
- 2012
84. Two-photon excitation in life sciences: neurotransmitter and fluorescence uncaging
- Author
-
Yves Lutz, Alexandre Specht, Sébastien Charon, Jean-Luc Vonesch, David Warther, Jean-François Nicoud, Frédéric Bolze, Attila Losonczy, Xiao-Hua Sun, Maurice Goeldner, Sylvestre Gug, and Pascal Kessler
- Subjects
chemistry.chemical_compound ,Two-photon excitation microscopy ,chemistry ,Photodissociation ,Biophysics ,Quantum yield ,Nanotechnology ,Neurotransmitter ,Fluorescence ,Excitation ,Molecular engineering - Abstract
We describe the molecular engineering of new highly efficient two-photon photolabile cages, based on dissymmetrical donor-acceptor and symmetrical donor-donor systems. Complete characterizations of these new cages, based on a biphenyl, fluorenyl or a 2,5-diphenylthienyl central core will be presented. In vitro photochemistry will be described (uncaging quantum yield, two-photon uncaging action cross-section,...) and we will then focus on biological results obtained in cell culture and on acute brain slices (with glutamate and fluorescence uncaging).
- Published
- 2011
85. Experience-dependent compartmentalized dendritic plasticity in rat hippocampal CA1 pyramidal neurons
- Author
-
Quan Wen, Jeffrey C. Magee, Judit K. Makara, and Attila Losonczy
- Subjects
Nervous system ,Cerebellum ,Potassium Channels ,Action Potentials ,Down-Regulation ,Hippocampal formation ,Environment ,Neuroscientist ,Memory ,medicine ,Animals ,CA1 Region, Hippocampal ,Systems neuroscience ,Neuronal Plasticity ,Chemistry ,General Neuroscience ,Pyramidal Cells ,Neurodegeneration ,Dendrites ,medicine.disease ,Dendritic filopodia ,Rats ,medicine.anatomical_structure ,nervous system ,Neuron ,Neuroscience - Abstract
Dendritic excitability is a plastic property of neurons. This study shows that exposure to an enriched environment increases propagation of dendritic sodium spikes in a subset of dendritic branches in CA1 pyramidal neurons. This effect is mediated by localized downregulation of A-type potassium channel function. The excitability of individual dendritic branches is a plastic property of neurons. We found that experience in an enriched environment increased propagation of dendritic Na+ spikes in a subset of individual dendritic branches in rat hippocampal CA1 pyramidal neurons and that this effect was mainly mediated by localized downregulation of A-type K+ channel function. Thus, dendritic plasticity might be used to store recent experience in individual branches of the dendritic arbor.
- Published
- 2009
86. Compartmentalized dendritic plasticity and input feature storage in neurons
- Author
-
Jeffrey C. Magee, Attila Losonczy, and Judit K. Makara
- Subjects
Male ,Models, Neurological ,Nonsynaptic plasticity ,Action Potentials ,Dendritic branch ,Biology ,Receptors, N-Methyl-D-Aspartate ,Rats, Sprague-Dawley ,Mice ,Metaplasticity ,medicine ,Animals ,Cell Shape ,Genetics ,Dendritic spike ,Multidisciplinary ,Neuronal Plasticity ,Pyramidal Cells ,Long-term potentiation ,Dendrites ,Rats ,medicine.anatomical_structure ,Shal Potassium Channels ,Synaptic plasticity ,NMDA receptor ,Soma ,Neuroscience ,Ion Channel Gating - Abstract
Although information storage in the central nervous system is thought to be primarily mediated by various forms of synaptic plasticity, other mechanisms, such as modifications in membrane excitability, are available. Local dendritic spikes are nonlinear voltage events that are initiated within dendritic branches by spatially clustered and temporally synchronous synaptic input. That local spikes selectively respond only to appropriately correlated input allows them to function as input feature detectors and potentially as powerful information storage mechanisms. However, it is currently unknown whether any effective form of local dendritic spike plasticity exists. Here we show that the coupling between local dendritic spikes and the soma of rat hippocampal CA1 pyramidal neurons can be modified in a branch-specific manner through an N-methyl-d-aspartate receptor (NMDAR)-dependent regulation of dendritic Kv4.2 potassium channels. These data suggest that compartmentalized changes in branch excitability could store multiple complex features of synaptic input, such as their spatio-temporal correlation. We propose that this ‘branch strength potentiation’ represents a previously unknown form of information storage that is distinct from that produced by changes in synaptic efficacy both at the mechanistic level and in the type of information stored. A newly discovered mechanism for synaptic plasticity whereby higher-order information can be stored in the forward propagation of local dendritic branch spikes is described. It is reported that coupling between branches and the soma is not static as previously thought, but that an associative form of branch plasticity allows neurons to encode the spatio-temporal correlation of inputs.
- Published
- 2007
87. Associative pairing enhances action potential back-propagation in radial oblique branches of CA1 pyramidal neurons
- Author
-
Sonia, Gasparini, Attila, Losonczy, Xixi, Chen, Daniel, Johnston, and Jeffrey C, Magee
- Subjects
Male ,Mice, Knockout ,Neuronal Plasticity ,Potassium Channels ,Pyramidal Cells ,Action Potentials ,Dendrites ,In Vitro Techniques ,Hippocampus ,Rats ,Rats, Sprague-Dawley ,Mice ,Barium ,Synapses ,Potassium Channel Blockers ,Animals ,Calcium ,Neuroscience - Abstract
Back-propagating action potentials (bAPs) are involved in associative synaptic plasticity and the modulation of dendritic excitability. We have used high-speed confocal and two-photon imaging to measure calcium and voltage signals associated with action potential propagation into oblique branches of CA1 pyramidal neurons in adult hippocampal slices. The spatial profile of the bAP-associated Ca(2+) influx was biphasic, with an initial increase in the proximity of the branch point followed by a progressive decrease. Voltage imaging in the branches showed that bAP amplitude was initially constant and then steadily declined with distance from the soma. To determine the role of transient K(+) channels in this profile, we used external Ba(2+) (150 microm) as a channel blocker, after characterizing its effect on A-type K(+) channels in the apical trunk. Bath application of Ba(2+) significantly reduced the A-type K(+) current in outside-out patches and nearly eliminated the distance-dependent decrease in bAP amplitude and its associated Ca(2+) signal. Finally, small amplitude bAPs at more distal oblique branch locations could be boosted by simultaneous branch depolarization, such that the paired Ca(2+) signal became nearly the same for proximal and distal oblique dendrites. These data suggest that dendritic K(+) channels regulate the amplitude of bAPs to create a dendritic Ca(2+) signal whose magnitude is inversely related to the electrotonic distance from the soma when bAPs are not associated with a significant amount of localized synaptic input. This distance-dependent Ca(2+) signal from bAPs, however, can be amplified and a strong associative signal is produced once the proper correlation between synaptic activation and AP output is achieved. We hypothesize that these two signals may be involved in the regulation of the expression and activity of dendritic voltage- and ligand-gated ion channels.
- Published
- 2007
88. Persistently active cannabinoid receptors mute a subpopulation of hippocampal interneurons
- Author
-
Attila Losonczy, Zoltan Nusser, and Ágota A. Biró
- Subjects
Male ,medicine.medical_specialty ,Cannabinoid receptor ,medicine.medical_treatment ,Morpholines ,Hippocampus ,Action Potentials ,Hippocampal formation ,Biology ,Naphthalenes ,Receptor, Cannabinoid, CB1 ,Interneurons ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Receptor ,Multidisciplinary ,Biological Sciences ,Receptors, GABA-A ,Endocannabinoid system ,Benzoxazines ,Rats ,Endocrinology ,Cannabinoid receptor antagonist ,GABAergic ,Cannabinoid ,Cholecystokinin ,Neuroscience - Abstract
Cortical information processing requires an orchestrated interaction between a large number of pyramidal cells and albeit fewer, but highly diverse GABAergic interneurons (INs). The diversity of INs is thought to reflect functional and structural specializations evolved to control distinct network operations. Consequently, specific cortical functions may be selectively modified by altering the input-output relationship of unique IN populations. Here, we report that persistently active cannabinoid receptors, the site of action of endocannabinoids, and the psychostimulants marijuana and hashish, switch off the output (mute) of a unique class of hippocampal INs. In paired recordings between cholecystokinin-immunopositive, mossy fiber-associated INs, and their target CA3 pyramidal cells, no postsynaptic currents could be evoked with single presynaptic action potentials or with repetitive stimulations at frequencies
- Published
- 2004
89. Reduction of excitatory postsynaptic responses by persistently active metabotropic glutamate receptors in the hippocampus
- Author
-
Peter Somogyi, Attila Losonczy, and Zoltan Nusser
- Subjects
Cyclopropanes ,Physiology ,Glycine ,Presynaptic Terminals ,Hippocampus ,Receptors, Metabotropic Glutamate ,Membrane Potentials ,Mice ,Postsynaptic potential ,Interneurons ,medicine ,Animals ,Axon ,Amino Acids ,Neuronal Plasticity ,Chemistry ,musculoskeletal, neural, and ocular physiology ,General Neuroscience ,Glutamate receptor ,Presynaptic receptors ,Excitatory Postsynaptic Potentials ,Mice, Inbred C57BL ,medicine.anatomical_structure ,nervous system ,Xanthenes ,Metabotropic glutamate receptor ,Excitatory postsynaptic potential ,Anticonvulsants ,Propionates ,Neuroscience ,Excitatory Amino Acid Antagonists - Abstract
The release of glutamate from axon terminals is under the control of a variety of presynaptic receptors, including several metabotropic glutamate receptors (mGluRs). Synaptically released glutamate can activate mGluRs within the same synapse where it was released and also at a distance following its diffusion from the synaptic cleft. It is unknown, however, whether the release of glutamate is under the control of persistently active mGluRs. We tested the contribution of mGluR activation to the excitatory postsynaptic responses recorded from several types of GABAergic interneuron in strata oriens/alveus of the mouse hippocampus. The application of 1 microM (alphaS)-alpha-amino-alpha-[(1S,2S)-2-carboxycyclopropyl]xanthine-9-propanoic acid (LY341495), a broad-spectrum mGluR (subtypes 2/3/7/8) antagonist at this concentration, increased evoked-excitatory postsynaptic current (eEPSC) amplitudes by 60% (n = 33). On identified cell types, LY341495 had either no effect (7 of 14 basket and 7 of 13 oriens-lacunosum moleculare, O-LM cells) or resulted in a 32 +/- 30% (mean +/- SD) increase in EPSC amplitudes recorded from basket cells and a seven-times greater (216 +/- 102%) enhancement of EPSCs in O-LM cells. The enhancement of the first EPSC of a high-frequency train indicates persistent mGluR activation. During antagonist application, the relative increase in EPSC amplitude evoked by the second and subsequent pulses in the train was not larger than that of the first EPSC, showing no further receptor activation by the released transmitter. The effect of mGluR subtype selective agonists [3 microM L(+)-2-amino-4-phosphonobutyric acid (L-AP4): mGluR4/8; 600 microM L-AP4: mGluR4/7/8; 1 microM (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IU): mGluR2/3] and an antagonist (0.2 microM LY341495: mGluR2/3/8) suggests that persistently active mGluR2/3/8 control the excitability of hippocampal network.
- Published
- 2003
90. Erratum: Corrigendum: Control of timing, rate and bursts of hippocampal place cells by dendritic and somatic inhibition
- Author
-
György Buzsáki, Jinhyun Kim, Boris V. Zemelman, Jeffrey C. Magee, Frances S. Chance, Attila Losonczy, and Sébastien Royer
- Subjects
Somatic cell ,General Neuroscience ,Biology ,Hippocampal formation ,Neuroscience - Abstract
Corrigendum: Control of timing, rate and bursts of hippocampal place cells by dendritic and somatic inhibition
- Published
- 2013
91. NADPH-diaphorase-positive neurons and pathways in the brain of the frog Rana esculenta
- Author
-
Attila Losonczy and Gyula Lázár
- Subjects
Embryology ,Pathology ,medicine.medical_specialty ,Olfactory Nerve ,Biology ,Diencephalon ,Nerve Fibers ,Species Specificity ,Neural Pathways ,Tegmentum ,medicine ,Animals ,Neurons ,Brain Mapping ,Cerebrum ,Solitary tract ,NADPH Dehydrogenase ,Brain ,Rana esculenta ,Cell Biology ,Anatomy ,Denervation ,Olfactory bulb ,medicine.anatomical_structure ,nervous system ,Dorsal column nuclei ,Raphe nuclei ,Tectum ,Developmental Biology - Abstract
We described the NADPH-diaphorase-containing neurons and fibres in the brain of the frog Rana esculenta. In the telencephalon stained cells occurred in the olfactory bulb, all subdivisions of the pallium, the diagonal band, the medial septum and the striatum. The olfactory glomeruli showed the most intense enzyme reaction. The neuropil of the accessory olfactory bulb was also heavily stained and this staining extended to the rostral diencephalon through the ventral lateral pallium. Fibre staining was less intense in the medial pallium and the medial septum. In the diencephalon, NADPH-diaphorase staining was concentrated in the middle third of this part of the brain. The stained cells were embedded in a dense network of thin, stained fibres and terminals in the lateral anterior and central thalamic nuclei. Faintly stained cells were present also in the posterior preoptic nucleus, anterior thalamic nucleus, nucleus of Bellonci, corpus geniculatum thalamicum and the suprachismatic nucleus. In the mesencephalon, heavily stained cells occurred in the nucleus profundus mesencephali, anterodorsal, anteroventral and especially in the posterodorsal tegmental nuclei. Neuronal staining was less intense in the optic tectum and the torus semicircularis. Thick, intensely stained fibres occupied the lateral part of the tegmentum and the 7th layer of the tectum. A loose network of thin fibres occupied the periventricular area and all tegmental nuclei. In the rhombencephalon, the reticular nuclei and the inferior raphe nucleus showed the most intense staining, while some cells in the nucleus of the solitary tract and the dorsal column nuclei were less intensely stained. Heavy staining of fibres was characteristic of the spinal trigeminal tract, the solitary tract and the reticulospinal pathway.
- Published
- 1999
92. Integrative Properties of Radial Oblique Dendrites in Hippocampal CA1 Pyramidal Neurons
- Author
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Attila Losonczy and Jeffrey C. Magee
- Subjects
Patch-Clamp Techniques ,Neuroscience(all) ,Glutamic Acid ,Hippocampal formation ,Receptors, N-Methyl-D-Aspartate ,Synaptic Transmission ,MOLNEURO ,Rats, Sprague-Dawley ,Animals ,Dendritic spike ,SYSBIO ,Chemistry ,General Neuroscience ,Pyramidal Cells ,Glutamate receptor ,Oblique case ,Excitatory Postsynaptic Potentials ,Dendrites ,Rats ,Synapses ,Spatial clustering ,Excitatory postsynaptic potential ,NMDA receptor ,Calcium Channels ,SYSNEURO ,Neuroscience - Abstract
Although radial oblique dendrites are a major synaptic input site in CA1 pyramidal neurons, little is known about their integrative properties. We have used multisite two-photon glutamate uncaging to deliver different spatiotemporal input patterns to single branches while simultaneously recording the uncaging-evoked excitatory postsynaptic potentials and local Ca2+ signals. Asynchronous input patterns sum linearly in spite of the spatial clustering and produce Ca2+ signals that are mediated by NMDA receptors (NMDARs). Appropriately timed and sized input patterns ( approximately 20 inputs within approximately 6 ms) produce a supralinear summation due to the initiation of a dendritic spike. The Ca2+ signals associated with synchronous input were larger and mediated by influx through both NMDARs and voltage-gated Ca2+ channels (VGCCs). The oblique spike is a fast Na+ spike whose duration is shaped by the coincident activation of NMDAR, VGCCs, and transient K+ currents. Our results suggest that individual branches can function as single integrative compartments.
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