@article{12288,
abstract = {To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo.},
author = {Sumser, Anton L and Jösch, Maximilian A and Jonas, Peter M and Ben Simon, Yoav},
issn = {2050-084X},
journal = {eLife},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
publisher = {eLife Sciences Publications},
title = {{Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling}},
doi = {10.7554/elife.79848},
volume = {11},
year = {2022},
}
@article{10763,
abstract = {AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory
synapses in the brain. Glutamate binding to the receptor’s ligand-binding domains (LBDs)
leads to ion channel activation and desensitization. Gating kinetics shape synaptic transmission
and are strongly modulated by transmembrane AMPAR regulatory proteins (TARPs)
through currently incompletely resolved mechanisms. Here, electron cryo-microscopy
structures of the GluA1/2 TARP-γ8 complex, in both open and desensitized states
(at 3.5 Å), reveal state-selective engagement of the LBDs by the large TARP-γ8 loop (‘β1’),
elucidating how this TARP stabilizes specific gating states. We further show how TARPs alter
channel rectification, by interacting with the pore helix of the selectivity filter. Lastly, we
reveal that the Q/R-editing site couples the channel constriction at the filter entrance to the
gate, and forms the major cation binding site in the conduction path. Our results provide a
mechanistic framework of how TARPs modulate AMPAR gating and conductance.},
author = {Herguedas, Beatriz and Kohegyi, Bianka K. and Dohrke, Jan Niklas and Watson, Jake and Zhang, Danyang and Ho, Hinze and Shaikh, Saher A. and Lape, Remigijus and Krieger, James M. and Greger, Ingo H.},
issn = {2041-1723},
journal = {Nature Communications},
publisher = {Springer Nature},
title = {{Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor}},
doi = {10.1038/s41467-022-28404-7},
volume = {13},
year = {2022},
}
@phdthesis{11196,
abstract = {One of the fundamental questions in Neuroscience is how the structure of synapses and their physiological properties are related. While synaptic transmission remains a dynamic process, electron microscopy provides images with comparably low temporal resolution (Studer et al., 2014). The current work overcomes this challenge and describes an improved “Flash and Freeze” technique (Watanabe et al., 2013a; Watanabe et al., 2013b) to study synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapses, using mouse acute brain slices and organotypic slices culture. The improved method allowed for selective stimulation of presynaptic mossy fiber boutons and the observation of synaptic vesicle pool dynamics at the active zones. Our results uncovered several intriguing morphological features of mossy fiber boutons. First, the docked vesicle pool was largely depleted (more than 70%) after stimulation, implying that the docked synaptic vesicles pool and readily releasable pool are vastly overlapping in mossy fiber boutons. Second, the synaptic vesicles are skewed towards larger diameters, displaying a wide range of sizes. An increase in the mean diameter of synaptic vesicles, after single and repetitive stimulation, suggests that smaller vesicles have a higher release probability. Third, we observed putative endocytotic structures after moderate light stimulation, matching the timing of previously described ultrafast endocytosis (Watanabe et al., 2013a; Delvendahl et al., 2016).
In addition, synaptic transmission depends on a sophisticated system of protein machinery and calcium channels (Südhof, 2013b), which amplifies the challenge in studying synaptic communication as these interactions can be potentially modified during synaptic plasticity. And although recent study elucidated the potential correlation between physiological and morphological properties of synapses during synaptic plasticity (Vandael et al., 2020), the molecular underpinning of it remains unknown. Thus, the presented work tries to overcome this challenge and aims to pinpoint changes in the molecular architecture at hippocampal mossy fiber bouton synapses during short- and long-term potentiation (STP and LTP), we combined chemical potentiation, with the application of a cyclic adenosine monophosphate agonist (i.e. forskolin) and freeze-fracture replica immunolabelling. This method allowed the localization of membrane-bound proteins with nanometer precision within the active zone, in particular, P/Q-type calcium channels and synaptic vesicle priming proteins Munc13-1/2. First, we found that the number of clusters of Munc13-1 in the mossy fiber bouton active zone increased significantly during STP, but decreased to lower than the control value during LTP. Secondly, although the distance between the calcium channels and Munc13-1s did not change after induction of STP, it shortened during the LTP phase. Additionally, forskolin did not affect Munc13-2 distribution during STP and LTP. These results indicate the existence of two distinct mechanisms that govern STP and LTP at mossy fiber bouton synapses: an increase in the readily realizable pool in the case of STP and a potential increase in release probability during LTP. “Flash and freeze” and functional electron microscopy, are versatile methods that can be successfully applied to intact brain circuits to study synaptic transmission even at the molecular level.
},
author = {Kim, Olena},
issn = {2663-337X},
pages = {132},
publisher = {Institute of Science and Technology Austria},
title = {{Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses}},
doi = {10.15479/at:ista:11196},
year = {2022},
}
@unpublished{11943,
abstract = {Complex wiring between neurons underlies the information-processing network enabling all brain functions, including cognition and memory. For understanding how the network is structured, processes information, and changes over time, comprehensive visualization of the architecture of living brain tissue with its cellular and molecular components would open up major opportunities. However, electron microscopy (EM) provides nanometre-scale resolution required for full in-silico reconstruction1–5, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches6–12 facilitating nanoscale visualization, but comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue. We developed an integrated imaging and analysis technology, adapting stimulated emission depletion (STED) microscopy6,13 in extracellularly labelled tissue14 for high SNR and near-isotropic resolution. Centrally, a two-stage deep-learning approach leveraged previously obtained information on sample structure to drastically reduce photo-burden and enable automated volumetric reconstruction down to single synapse level. Live reconstruction provides unbiased analysis of tissue architecture across time in relation to functional activity and targeted activation, and contextual understanding of molecular labelling. This adoptable technology will facilitate novel insights into the dynamic functional architecture of living brain tissue.},
author = {Velicky, Philipp and Miguel Villalba, Eder and Michalska, Julia M and Wei, Donglai and Lin, Zudi and Watson, Jake and Troidl, Jakob and Beyer, Johanna and Ben Simon, Yoav and Sommer, Christoph M and Jahr, Wiebke and Cenameri, Alban and Broichhagen, Johannes and Grant, Seth G. N. and Jonas, Peter M and Novarino, Gaia and Pfister, Hanspeter and Bickel, Bernd and Danzl, Johann G},
booktitle = {bioRxiv},
publisher = {Cold Spring Harbor Laboratory},
title = {{Saturated reconstruction of living brain tissue}},
doi = {10.1101/2022.03.16.484431},
year = {2022},
}
@unpublished{11950,
abstract = {Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS leverages fixation-compatible extracellular labeling and advanced optical readout, in particular stimulated-emission depletion and expansion microscopy, to comprehensively delineate cellular structures. It enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. Applying CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal the system’s molecularly informed ultrastructure across spatial scales and assess local connectivity by reconstructing and quantifying the synaptic input and output structure of identified neurons.},
author = {Michalska, Julia M and Lyudchik, Julia and Velicky, Philipp and Korinkova, Hana and Watson, Jake and Cenameri, Alban and Sommer, Christoph M and Venturino, Alessandro and Roessler, Karl and Czech, Thomas and Siegert, Sandra and Novarino, Gaia and Jonas, Peter M and Danzl, Johann G},
booktitle = {bioRxiv},
publisher = {Cold Spring Harbor Laboratory},
title = {{Uncovering brain tissue architecture across scales with super-resolution light microscopy}},
doi = {10.1101/2022.08.17.504272},
year = {2022},
}
@article{15273,
abstract = {Synapses of glutamatergic mossy fibers (MFs) onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC’s large dendritic brush. Using mouse brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBCs. The source of this ambient glutamate was spontaneous, spike-independent exocytosis from the MF terminal, and its level was dependent on activity of glutamate transporters EAAT1–2. Increasing levels of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs and altered the phase of responses to in vivo-like synaptic activity. Unlike classical fast synapses, receptors at the UBC synapse are virtually always exposed to a significant level of glutamate, which varies in a graded manner during transmission.},
author = {Balmer, Timothy S and Borges Merjane, Carolina and Trussell, Laurence O},
issn = {2050-084X},
journal = {eLife},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
publisher = {eLife Sciences Publications},
title = {{Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse}},
doi = {10.7554/elife.63819},
volume = {10},
year = {2021},
}
@article{9329,
abstract = {Background: To understand information coding in single neurons, it is necessary to analyze subthreshold synaptic events, action potentials (APs), and their interrelation in different behavioral states. However, detecting excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and variable time course of synaptic events.
New method: We developed a method for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure), which combines concepts of supervised machine learning and optimal Wiener filtering. Experts were asked to manually score short epochs of data. The algorithm was trained to obtain the optimal filter coefficients of a Wiener filter and the optimal detection threshold. Scored and unscored data were then processed with the optimal filter, and events were detected as peaks above threshold.
Results: We challenged MOD with EPSP traces in vivo in mice during spatial navigation and EPSC traces in vitro in slices under conditions of enhanced transmitter release. The area under the curve (AUC) of the receiver operating characteristics (ROC) curve was, on average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection accuracy and efficiency.
Comparison with existing methods: When benchmarked using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution, and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but showed comparable (template-fit, deconvolution) or higher (Bayesian) computational efficacy.
Conclusions: MOD may become an important new tool for large-scale, real-time analysis of synaptic activity.},
author = {Zhang, Xiaomin and Schlögl, Alois and Vandael, David H and Jonas, Peter M},
issn = {1872-678X},
journal = {Journal of Neuroscience Methods},
number = {6},
publisher = {Elsevier},
title = {{MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo}},
doi = {10.1016/j.jneumeth.2021.109125},
volume = {357},
year = {2021},
}
@article{9549,
abstract = {AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning1. A diverse array of AMPAR signalling complexes are established by receptor auxiliary subunits, which associate with the AMPAR in various combinations to modulate trafficking, gating and synaptic strength2. However, their mechanisms of action are poorly understood. Here we determine cryo-electron microscopy structures of the heteromeric GluA1–GluA2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states. Two TARP-γ8 and two CNIH2 subunits insert at distinct sites beneath the ligand-binding domains of the receptor, with site-specific lipids shaping each interaction and affecting the gating regulation of the AMPARs. Activation of the receptor leads to asymmetry between GluA1 and GluA2 along the ion conduction path and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, promoting the active-state conformation. In addition, both TARP-γ8 and CNIH2 pivot towards the pore exit upon activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this endoplasmic reticulum-export factor into a powerful AMPAR modulator that is capable of providing hippocampal pyramidal neurons with their integrative synaptic properties. },
author = {Zhang, Danyang and Watson, Jake and Matthews, Peter M. and Cais, Ondrej and Greger, Ingo H.},
issn = {1476-4687},
journal = {Nature},
pages = {454--458},
publisher = {Springer Nature},
title = {{Gating and modulation of a hetero-octameric AMPA glutamate receptor}},
doi = {10.1038/s41586-021-03613-0},
volume = {594},
year = {2021},
}
@article{9778,
abstract = {The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons. To directly test cooperativity and associativity, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating non-overlapping mossy fiber inputs converging onto single CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly, mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only minimal PTP after combined pre- and postsynaptic high-frequency stimulation with intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels, group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire of synaptic computations, implementing a brake on mossy fiber detonation and a “smart teacher” function of hippocampal mossy fiber synapses.},
author = {Vandael, David H and Okamoto, Yuji and Jonas, Peter M},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {general physics and astronomy, general biochemistry, genetics and molecular biology, general chemistry},
number = {1},
publisher = {Springer},
title = {{Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses}},
doi = {10.1038/s41467-021-23153-5},
volume = {12},
year = {2021},
}
@article{9985,
abstract = {AMPA receptor (AMPAR) abundance and positioning at excitatory synapses regulates the strength of transmission. Changes in AMPAR localisation can enact synaptic plasticity, allowing long-term information storage, and is therefore tightly controlled. Multiple mechanisms regulating AMPAR synaptic anchoring have been described, but with limited coherence or comparison between reports, our understanding of this process is unclear. Here, combining synaptic recordings from mouse hippocampal slices and super-resolution imaging in dissociated cultures, we compare the contributions of three AMPAR interaction domains controlling transmission at hippocampal CA1 synapses. We show that the AMPAR C-termini play only a modulatory role, whereas the extracellular N-terminal domain (NTD) and PDZ interactions of the auxiliary subunit TARP γ8 are both crucial, and each is sufficient to maintain transmission. Our data support a model in which γ8 accumulates AMPARs at the postsynaptic density, where the NTD further tunes their positioning. This interplay between cytosolic (TARP γ8) and synaptic cleft (NTD) interactions provides versatility to regulate synaptic transmission and plasticity.},
author = {Watson, Jake and Pinggera, Alexandra and Ho, Hinze and Greger, Ingo H.},
issn = {2041-1723},
journal = {Nature Communications},
number = {1},
publisher = {Nature Publishing Group},
title = {{AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions}},
doi = {10.1038/s41467-021-25281-4},
volume = {12},
year = {2021},
}
@article{9438,
abstract = {Rigorous investigation of synaptic transmission requires analysis of unitary synaptic events by simultaneous recording from presynaptic terminals and postsynaptic target neurons. However, this has been achieved at only a limited number of model synapses, including the squid giant synapse and the mammalian calyx of Held. Cortical presynaptic terminals have been largely inaccessible to direct presynaptic recording, due to their small size. Here, we describe a protocol for improved subcellular patch-clamp recording in rat and mouse brain slices, with the synapse in a largely intact environment. Slice preparation takes ~2 h, recording ~3 h and post hoc morphological analysis 2 d. Single presynaptic hippocampal mossy fiber terminals are stimulated minimally invasively in the bouton-attached configuration, in which the cytoplasmic content remains unperturbed, or in the whole-bouton configuration, in which the cytoplasmic composition can be precisely controlled. Paired pre–postsynaptic recordings can be integrated with biocytin labeling and morphological analysis, allowing correlative investigation of synapse structure and function. Paired recordings can be obtained from mossy fiber terminals in slices from both rats and mice, implying applicability to genetically modified synapses. Paired recordings can also be performed together with axon tract stimulation or optogenetic activation, allowing comparison of unitary and compound synaptic events in the same target cell. Finally, paired recordings can be combined with spontaneous event analysis, permitting collection of miniature events generated at a single identified synapse. In conclusion, the subcellular patch-clamp techniques detailed here should facilitate analysis of biophysics, plasticity and circuit function of cortical synapses in the mammalian central nervous system.},
author = {Vandael, David H and Okamoto, Yuji and Borges Merjane, Carolina and Vargas Barroso, Victor M and Suter, Benjamin and Jonas, Peter M},
issn = {1750-2799},
journal = {Nature Protocols},
number = {6},
pages = {2947–2967},
publisher = {Springer Nature},
title = {{Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses}},
doi = {10.1038/s41596-021-00526-0},
volume = {16},
year = {2021},
}
@article{10816,
abstract = {Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks.},
author = {Guzmán, José and Schlögl, Alois and Espinoza Martinez, Claudia and Zhang, Xiaomin and Suter, Benjamin and Jonas, Peter M},
issn = {2662-8457},
journal = {Nature Computational Science},
keywords = {general medicine},
number = {12},
pages = {830--842},
publisher = {Springer Nature},
title = {{How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network}},
doi = {10.1038/s43588-021-00157-1},
volume = {1},
year = {2021},
}
@misc{10110,
abstract = {Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks.},
author = {Guzmán, José and Schlögl, Alois and Espinoza Martinez, Claudia and Zhang, Xiaomin and Suter, Benjamin and Jonas, Peter M},
publisher = {IST Austria},
title = {{How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network}},
doi = {10.15479/AT:ISTA:10110},
year = {2021},
}
@article{9437,
abstract = {The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation.},
author = {Bhandari, Pradeep and Vandael, David H and Fernández-Fernández, Diego and Fritzius, Thorsten and Kleindienst, David and Önal, Hüseyin C and Montanaro-Punzengruber, Jacqueline-Claire and Gassmann, Martin and Jonas, Peter M and Kulik, Akos and Bettler, Bernhard and Shigemoto, Ryuichi and Koppensteiner, Peter},
issn = {2050-084X},
journal = {eLife},
publisher = {eLife Sciences Publications},
title = {{GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals}},
doi = {10.7554/ELIFE.68274},
volume = {10},
year = {2021},
}
@article{8001,
abstract = {Post-tetanic potentiation (PTP) is an attractive candidate mechanism for hippocampus-dependent short-term memory. Although PTP has a uniquely large magnitude at hippocampal mossy fiber-CA3 pyramidal neuron synapses, it is unclear whether it can be induced by natural activity and whether its lifetime is sufficient to support short-term memory. We combined in vivo recordings from granule cells (GCs), in vitro paired recordings from mossy fiber terminals and postsynaptic CA3 neurons, and “flash and freeze” electron microscopy. PTP was induced at single synapses and showed a low induction threshold adapted to sparse GC activity in vivo. PTP was mainly generated by enlargement of the readily releasable pool of synaptic vesicles, allowing multiplicative interaction with other plasticity forms. PTP was associated with an increase in the docked vesicle pool, suggesting formation of structural “pool engrams.” Absence of presynaptic activity extended the lifetime of the potentiation, enabling prolonged information storage in the hippocampal network.},
author = {Vandael, David H and Borges Merjane, Carolina and Zhang, Xiaomin and Jonas, Peter M},
issn = {10974199},
journal = {Neuron},
number = {3},
pages = {509--521},
publisher = {Elsevier},
title = {{Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation}},
doi = {10.1016/j.neuron.2020.05.013},
volume = {107},
year = {2020},
}
@article{8261,
abstract = {Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal CA3 region, but how they process spatial information remains enigmatic. To examine the role of GCs in spatial coding, we measured excitatory postsynaptic potentials (EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt. Intracellular recording from morphologically identified GCs revealed that most cells were active, but activity level varied over a wide range. Whereas only ∼5% of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus, the GC population broadly encodes spatial information, but only a subset relays this information to the CA3 network. Fourier analysis indicated that GCs received conjunctive place-grid-like synaptic input, suggesting code conversion in single neurons. GC firing was correlated with dendritic complexity and intrinsic excitability, but not extrinsic excitatory input or dendritic cable properties. Thus, functional maturation may control input-output transformation and spatial code conversion.},
author = {Zhang, Xiaomin and Schlögl, Alois and Jonas, Peter M},
issn = {0896-6273},
journal = {Neuron},
number = {6},
pages = {1212--1225},
publisher = {Elsevier},
title = {{Selective routing of spatial information flow from input to output in hippocampal granule cells}},
doi = {10.1016/j.neuron.2020.07.006},
volume = {107},
year = {2020},
}
@article{7473,
abstract = {How structural and functional properties of synapses relate to each other is a fundamental question in neuroscience. Electrophysiology has elucidated mechanisms of synaptic transmission, and electron microscopy (EM) has provided insight into morphological properties of synapses. Here we describe an enhanced method for functional EM (“flash and freeze”), combining optogenetic stimulation with high-pressure freezing. We demonstrate that the improved method can be applied to intact networks in acute brain slices and organotypic slice cultures from mice. As a proof of concept, we probed vesicle pool changes during synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapse. Our findings show overlap of the docked vesicle pool and the functionally defined readily releasable pool and provide evidence of fast endocytosis at this synapse. Functional EM with acute slices and slice cultures has the potential to reveal the structural and functional mechanisms of transmission in intact, genetically perturbed, and disease-affected synapses.},
author = {Borges Merjane, Carolina and Kim, Olena and Jonas, Peter M},
issn = {0896-6273},
journal = {Neuron},
pages = {992--1006},
publisher = {Elsevier},
title = {{Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices}},
doi = {10.1016/j.neuron.2019.12.022},
volume = {105},
year = {2020},
}
@inbook{19989,
abstract = {Neurone empfangen Eingangssignale, konvertieren diese in Aktionspotenziale und generieren schließlich Ausgangssignale auf ihren Zielzellen. Dabei sind die zu überwindenden räumlichen Distanzen oft groß. Daher ist entscheidend, dass elektrische Signale in Nervenzellen schnell von einem zum anderen Ort geleitet werden können. Diese wichtige Aufgabe erfüllt das Axon, der „Ausgangsfortsatz“ der Nervenzelle. Für die schnelle Leitung des Aktionspotenzials sind sowohl die passiven Eigenschaften des axonalen Kabels als auch die aktiven Eigenschaften der Zellmembran von entscheidender Bedeutung. Die Evolution bedient sich zweier Tricks, um die Leitungsgeschwindigkeit des Aktionspotenzials zu maximieren. Der eine Trick ist die Zunahme des Axondurchmessers. Der andere Trick ist die Ausbildung von Markscheiden. Dies führt bei nahezu gleichem Platzbedarf zu einer Zunahme der Leistungsgeschwindigkeit um fast zwei Größenordnungen. Die Aktionspotenzialleitung an myelinisierten Axonen erfolgt „saltatorisch“.},
author = {Jonas, Peter M},
booktitle = {Physiologie des Menschen},
isbn = {9783662564677},
issn = {2512-5214},
pages = {72--82},
publisher = {Springer Nature},
title = {{Aktionspotenzial: Fortleitung im Axon}},
doi = {10.1007/978-3-662-56468-4_7},
year = {2019},
}
@article{7405,
abstract = {Biophysical modeling of neuronal networks helps to integrate and interpret rapidly growing and disparate experimental datasets at multiple scales. The NetPyNE tool (www.netpyne.org) provides both programmatic and graphical interfaces to develop data-driven multiscale network models in NEURON. NetPyNE clearly separates model parameters from implementation code. Users provide specifications at a high level via a standardized declarative language, for example connectivity rules, to create millions of cell-to-cell connections. NetPyNE then enables users to generate the NEURON network, run efficiently parallelized simulations, optimize and explore network parameters through automated batch runs, and use built-in functions for visualization and analysis – connectivity matrices, voltage traces, spike raster plots, local field potentials, and information theoretic measures. NetPyNE also facilitates model sharing by exporting and importing standardized formats (NeuroML and SONATA). NetPyNE is already being used to teach computational neuroscience students and by modelers to investigate brain regions and phenomena.},
author = {Dura-Bernal, Salvador and Suter, Benjamin and Gleeson, Padraig and Cantarelli, Matteo and Quintana, Adrian and Rodriguez, Facundo and Kedziora, David J and Chadderdon, George L and Kerr, Cliff C and Neymotin, Samuel A and McDougal, Robert A and Hines, Michael and Shepherd, Gordon MG and Lytton, William W},
issn = {2050-084X},
journal = {eLife},
publisher = {eLife Sciences Publications},
title = {{NetPyNE, a tool for data-driven multiscale modeling of brain circuits}},
doi = {10.7554/elife.44494},
volume = {8},
year = {2019},
}
@inproceedings{11222,
author = {Kim, Olena and Borges Merjane, Carolina and Jonas, Peter M},
booktitle = {Intrinsic Activity},
issn = {2309-8503},
keywords = {hippocampus, mossy fibers, readily releasable pool, electron microscopy},
location = {Innsbruck, Austria},
number = {Suppl. 1},
publisher = {Austrian Pharmacological Society},
title = {{Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy}},
doi = {10.25006/ia.7.s1-a3.27},
volume = {7},
year = {2019},
}