TY - JOUR AB - A puzzling property of synaptic transmission, originally established at the neuromuscular junction, is that the time course of transmitter release is independent of the extracellular Ca2+ concentration ([Ca2+]o), whereas the rate of release is highly [Ca2+]o-dependent. Here, we examine the time course of release at inhibitory basket cell-Purkinje cell synapses and show that it is independent of [Ca2+]o. Modeling of Ca2+-dependent transmitter release suggests that the invariant time course of release critically depends on tight coupling between Ca2+ channels and release sensors. Experiments with exogenous Ca2+ chelators reveal that channel-sensor coupling at basket cell-Purkinje cell synapses is very tight, with a mean distance of 10–20 nm. Thus, tight channel-sensor coupling provides a mechanistic explanation for the apparent [Ca2+]o independence of the time course of release. AU - Arai, Itaru AU - Jonas, Peter M ID - 2031 JF - eLife TI - Nanodomain coupling explains Ca^2+ independence of transmitter release time course at a fast central synapse VL - 3 ER - TY - JOUR AB - The hippocampus mediates several higher brain functions, such as learning, memory, and spatial coding. The input region of the hippocampus, the dentate gyrus, plays a critical role in these processes. Several lines of evidence suggest that the dentate gyrus acts as a preprocessor of incoming information, preparing it for subsequent processing in CA3. For example, the dentate gyrus converts input from the entorhinal cortex, where cells have multiple spatial fields, into the spatially more specific place cell activity characteristic of the CA3 region. Furthermore, the dentate gyrus is involved in pattern separation, transforming relatively similar input patterns into substantially different output patterns. Finally, the dentate gyrus produces a very sparse coding scheme in which only a very small fraction of neurons are active at any one time. AU - Jonas, Peter M AU - Lisman, John ID - 2041 JF - Frontiers in Neural Circuits TI - Structure, function and plasticity of hippocampal dentate gyrus microcircuits VL - 8 ER - TY - JOUR AB - The success story of fast-spiking, parvalbumin-positive (PV+) GABAergic interneurons (GABA, γ-aminobutyric acid) in the mammalian central nervous system is noteworthy. In 1995, the properties of these interneurons were completely unknown. Twenty years later, thanks to the massive use of subcellular patch-clamp techniques, simultaneous multiple-cell recording, optogenetics, in vivo measurements, and computational approaches, our knowledge about PV+ interneurons became more extensive than for several types of pyramidal neurons. These findings have implications beyond the “small world” of basic research on GABAergic cells. For example, the results provide a first proof of principle that neuroscientists might be able to close the gaps between the molecular, cellular, network, and behavioral levels, representing one of the main challenges at the present time. Furthermore, the results may form the basis for PV+ interneurons as therapeutic targets for brain disease in the future. However, much needs to be learned about the basic function of these interneurons before clinical neuroscientists will be able to use PV+ interneurons for therapeutic purposes. AU - Hu, Hua AU - Gan, Jian AU - Jonas, Peter M ID - 2062 IS - 6196 JF - Science TI - Fast-spiking parvalbumin^+ GABAergic interneurons: From cellular design to microcircuit function VL - 345 ER - TY - JOUR AB - Neuronal ectopia, such as granule cell dispersion (GCD) in temporal lobe epilepsy (TLE), has been assumed to result from a migration defect during development. Indeed, recent studies reported that aberrant migration of neonatal-generated dentate granule cells (GCs) increased the risk to develop epilepsy later in life. On the contrary, in the present study, we show that fully differentiated GCs become motile following the induction of epileptiform activity, resulting in GCD. Hippocampal slice cultures from transgenic mice expressing green fluorescent protein in differentiated, but not in newly generated GCs, were incubated with the glutamate receptor agonist kainate (KA), which induced GC burst activity and GCD. Using real-time microscopy, we observed that KA-exposed, differentiated GCs translocated their cell bodies and changed their dendritic organization. As found in human TLE, KA application was associated with decreased expression of the extracellular matrix protein Reelin, particularly in hilar interneurons. Together these findings suggest that KA-induced motility of differentiated GCs contributes to the development of GCD and establish slice cultures as a model to study neuronal changes induced by epileptiform activity. AU - Chai, Xuejun AU - Münzner, Gert AU - Zhao, Shanting AU - Tinnes, Stefanie AU - Kowalski, Janina AU - Häussler, Ute AU - Young, Christina AU - Haas, Carola AU - Frotscher, Michael ID - 2164 IS - 8 JF - Cerebral Cortex TI - Epilepsy-induced motility of differentiated neurons VL - 24 ER - TY - JOUR AB - Electron microscopy (EM) allows for the simultaneous visualization of all tissue components at high resolution. However, the extent to which conventional aldehyde fixation and ethanol dehydration of the tissue alter the fine structure of cells and organelles, thereby preventing detection of subtle structural changes induced by an experiment, has remained an issue. Attempts have been made to rapidly freeze tissue to preserve native ultrastructure. Shock-freezing of living tissue under high pressure (high-pressure freezing, HPF) followed by cryosubstitution of the tissue water avoids aldehyde fixation and dehydration in ethanol; the tissue water is immobilized in â ̂1/450 ms, and a close-to-native fine structure of cells, organelles and molecules is preserved. Here we describe a protocol for HPF that is useful to monitor ultrastructural changes associated with functional changes at synapses in the brain but can be applied to many other tissues as well. The procedure requires a high-pressure freezer and takes a minimum of 7 d but can be paused at several points. AU - Studer, Daniel AU - Zhao, Shanting AU - Chai, Xuejun AU - Jonas, Peter M AU - Graber, Werner AU - Nestel, Sigrun AU - Frotscher, Michael ID - 2176 IS - 6 JF - Nature Protocols TI - Capture of activity-induced ultrastructural changes at synapses by high-pressure freezing of brain tissue VL - 9 ER - TY - JOUR AB - Intracellular electrophysiological recordings provide crucial insights into elementary neuronal signals such as action potentials and synaptic currents. Analyzing and interpreting these signals is essential for a quantitative understanding of neuronal information processing, and requires both fast data visualization and ready access to complex analysis routines. To achieve this goal, we have developed Stimfit, a free software package for cellular neurophysiology with a Python scripting interface and a built-in Python shell. The program supports most standard file formats for cellular neurophysiology and other biomedical signals through the Biosig library. To quantify and interpret the activity of single neurons and communication between neurons, the program includes algorithms to characterize the kinetics of presynaptic action potentials and postsynaptic currents, estimate latencies between pre- and postsynaptic events, and detect spontaneously occurring events. We validate and benchmark these algorithms, give estimation errors, and provide sample use cases, showing that Stimfit represents an efficient, accessible and extensible way to accurately analyze and interpret neuronal signals. AU - Guzmán, José AU - Schlögl, Alois AU - Schmidt Hieber, Christoph ID - 2230 IS - FEB JF - Frontiers in Neuroinformatics SN - 16625196 TI - Stimfit: Quantifying electrophysiological data with Python VL - 8 ER - TY - JOUR AB - Fast-spiking, parvalbumin-expressing GABAergic interneurons, a large proportion of which are basket cells (BCs), have a key role in feedforward and feedback inhibition, gamma oscillations and complex information processing. For these functions, fast propagation of action potentials (APs) from the soma to the presynaptic terminals is important. However, the functional properties of interneuron axons remain elusive. We examined interneuron axons by confocally targeted subcellular patch-clamp recording in rat hippocampal slices. APs were initiated in the proximal axon ∼20 μm from the soma and propagated to the distal axon with high reliability and speed. Subcellular mapping revealed a stepwise increase of Na^+ conductance density from the soma to the proximal axon, followed by a further gradual increase in the distal axon. Active cable modeling and experiments with partial channel block revealed that low axonal Na^+ conductance density was sufficient for reliability, but high Na^+ density was necessary for both speed of propagation and fast-spiking AP phenotype. Our results suggest that a supercritical density of Na^+ channels compensates for the morphological properties of interneuron axons (small segmental diameter, extensive branching and high bouton density), ensuring fast AP propagation and high-frequency repetitive firing. AU - Hu, Hua AU - Jonas, Peter M ID - 2228 IS - 5 JF - Nature Neuroscience SN - 10976256 TI - A supercritical density of Na^+ channels ensures fast signaling in GABAergic interneuron axons VL - 17 ER - TY - JOUR AB - The distance between Ca^2+ channels and release sensors determines the speed and efficacy of synaptic transmission. Tight "nanodomain" channel-sensor coupling initiates transmitter release at synapses in the mature brain, whereas loose "microdomain" coupling appears restricted to early developmental stages. To probe the coupling configuration at a plastic synapse in the mature central nervous system, we performed paired recordings between mossy fiber terminals and CA3 pyramidal neurons in rat hippocampus. Millimolar concentrations of both the fast Ca^2+ chelator BAPTA [1,2-bis(2-aminophenoxy)ethane- N,N, N′,N′-tetraacetic acid] and the slow chelator EGTA efficiently suppressed transmitter release, indicating loose coupling between Ca^2+ channels and release sensors. Loose coupling enabled the control of initial release probability by fast endogenous Ca^2+ buffers and the generation of facilitation by buffer saturation. Thus, loose coupling provides the molecular framework for presynaptic plasticity. AU - Vyleta, Nicholas AU - Jonas, Peter M ID - 2229 IS - 6171 JF - Science SN - 00368075 TI - Loose coupling between Ca^2+ channels and release sensors at a plastic hippocampal synapse VL - 343 ER - TY - JOUR AB - Theta-gamma network oscillations are thought to represent key reference signals for information processing in neuronal ensembles, but the underlying synaptic mechanisms remain unclear. To address this question, we performed whole-cell (WC) patch-clamp recordings from mature hippocampal granule cells (GCs) in vivo in the dentate gyrus of anesthetized and awake rats. GCs in vivo fired action potentials at low frequency, consistent with sparse coding in the dentate gyrus. GCs were exposed to barrages of fast AMPAR-mediated excitatory postsynaptic currents (EPSCs), primarily relayed from the entorhinal cortex, and inhibitory postsynaptic currents (IPSCs), presumably generated by local interneurons. EPSCs exhibited coherence with the field potential predominantly in the theta frequency band, whereas IPSCs showed coherence primarily in the gamma range. Action potentials in GCs were phase locked to network oscillations. Thus, theta-gamma-modulated synaptic currents may provide a framework for sparse temporal coding of information in the dentate gyrus. AU - Pernia-Andrade, Alejandro AU - Jonas, Peter M ID - 2254 IS - 1 JF - Neuron SN - 08966273 TI - Theta-gamma-modulated synaptic currents in hippocampal granule cells in vivo define a mechanism for network oscillations VL - 81 ER - TY - JOUR AB - GABAergic inhibitory interneurons control fundamental aspects of neuronal network function. Their functional roles are assumed to be defined by the identity of their input synapses, the architecture of their dendritic tree, the passive and active membrane properties and finally the nature of their postsynaptic targets. Indeed, interneurons display a high degree of morphological and physiological heterogeneity. However, whether their morphological and physiological characteristics are correlated and whether interneuron diversity can be described by a continuum of GABAergic cell types or by distinct classes has remained unclear. Here we perform a detailed morphological and physiological characterization of GABAergic cells in the dentate gyrus, the input region of the hippocampus. To achieve an unbiased and efficient sampling and classification we used knock-in mice expressing the enhanced green fluorescent protein (eGFP) in glutamate decarboxylase 67 (GAD67)-positive neurons and performed cluster analysis. We identified five interneuron classes, each of them characterized by a distinct set of anatomical and physiological parameters. Cross-correlation analysis further revealed a direct relation between morphological and physiological properties indicating that dentate gyrus interneurons fall into functionally distinct classes which may differentially control neuronal network activity. AU - Hosp, Jonas AU - Strüber, Michael AU - Yanagawa, Yuchio AU - Obata, Kunihiko AU - Vida, Imre AU - Jonas, Peter M AU - Bartos, Marlene ID - 2285 IS - 2 JF - Hippocampus TI - Morpho-physiological criteria divide dentate gyrus interneurons into classes VL - 23 ER - TY - JOUR AB - Stimfit is a free cross-platform software package for viewing and analyzing electrophysiological data. It supports most standard file types for cellular neurophysiology and other biomedical formats. Its analysis algorithms have been used and validated in several experimental laboratories. Its embedded Python scripting interface makes Stimfit highly extensible and customizable. AU - Schlögl, Alois AU - Jonas, Peter M AU - Schmidt-Hieber, C. AU - Guzman, S. J. ID - 10396 IS - SI-1-Track-G JF - Biomedical Engineering / Biomedizinische Technik KW - biomedical engineering KW - data analysis KW - free software SN - 0013-5585 TI - Stimfit: A fast visualization and analysis environment for cellular neurophysiology VL - 58 ER - TY - JOUR AB - Spontaneous postsynaptic currents (PSCs) provide key information about the mechanisms of synaptic transmission and the activity modes of neuronal networks. However, detecting spontaneous PSCs in vitro and in vivo has been challenging, because of the small amplitude, the variable kinetics, and the undefined time of generation of these events. Here, we describe a, to our knowledge, new method for detecting spontaneous synaptic events by deconvolution, using a template that approximates the average time course of spontaneous PSCs. A recorded PSC trace is deconvolved from the template, resulting in a series of delta-like functions. The maxima of these delta-like events are reliably detected, revealing the precise onset times of the spontaneous PSCs. Among all detection methods, the deconvolution-based method has a unique temporal resolution, allowing the detection of individual events in high-frequency bursts. Furthermore, the deconvolution-based method has a high amplitude resolution, because deconvolution can substantially increase the signal/noise ratio. When tested against previously published methods using experimental data, the deconvolution-based method was superior for spontaneous PSCs recorded in vivo. Using the high-resolution deconvolution-based detection algorithm, we show that the frequency of spontaneous excitatory postsynaptic currents in dentate gyrus granule cells is 4.5 times higher in vivo than in vitro. AU - Pernia-Andrade, Alejandro AU - Goswami, Sarit AU - Stickler, Yvonne AU - Fröbe, Ulrich AU - Schlögl, Alois AU - Jonas, Peter M ID - 2954 IS - 7 JF - Biophysical Journal TI - A deconvolution based method with high sensitivity and temporal resolution for detection of spontaneous synaptic currents in vitro and in vivo VL - 103 ER - TY - JOUR AB - The coupling between presynaptic Ca^(2+) channels and Ca^(2+) sensors of exocytosis is a key determinant of synaptic transmission. Evoked release from parvalbumin (PV)-expressing interneurons is triggered by nanodomain coupling of P/Q-type Ca^(2+) channels, whereas release from cholecystokinin (CCK)-containing interneurons is generated by microdomain coupling of N-type channels. Nanodomain coupling has several functional advantages, including speed and efficacy of transmission. One potential disadvantage is that stochastic opening of presynaptic Ca^(2+) channels may trigger spontaneous transmitter release. We addressed this possibility in rat hippocampal granule cells, which receive converging inputs from different inhibitory sources. Both reduction of extracellular Ca^(2+) concentration and the unselective Ca^(2+) channel blocker Cd^(2+) reduced the frequency of miniature IPSCs (mIPSCs) in granule cells by ~50%, suggesting that the opening of presynaptic Ca^(2+) channels contributes to spontaneous release. Application of the selective P/Q-type Ca^(2+) channel blocker ω-agatoxin IVa had no detectable effects, whereas both the N-type blocker ω-conotoxin GVIa and the L-type blocker nimodipine reduced mIPSC frequency. Furthermore, both the fast Ca^(2+) chelator BAPTA-AM and the slow chelator EGTA-AM reduced the mIPSC frequency, suggesting that Ca^(2+)-dependent spontaneous release is triggered by microdomain rather than nanodomain coupling. The CB_(1) receptor agonist WIN 55212-2 also decreased spontaneous release; this effect was occluded by prior application of ω-conotoxin GVIa, suggesting that a major fraction of Ca^(2+)-dependent spontaneous release was generated at the terminals of CCK-expressing interneurons. Tonic inhibition generated by spontaneous opening of presynaptic N- and L-type Ca^(2+) channels may be important for hippocampal information processing. AU - Goswami, Sarit AU - Bucurenciu, Iancu AU - Jonas, Peter M ID - 2969 IS - 41 JF - Journal of Neuroscience TI - Miniature IPSCs in hippocampal granule cells are triggered by voltage-gated Ca^(2+) channels via microdomain coupling VL - 32 ER - TY - JOUR AB - Voltage-activated Ca(2+) channels (VACCs) mediate Ca(2+) influx to trigger action potential-evoked neurotransmitter release, but the mechanism by which Ca(2+) regulates spontaneous transmission is unclear. We found that VACCs are the major physiological triggers for spontaneous release at mouse neocortical inhibitory synapses. Moreover, despite the absence of a synchronizing action potential, we found that spontaneous fusion of a GABA-containing vesicle required the activation of multiple tightly coupled VACCs of variable type. AU - Williams, Courtney AU - Chen, Wenyan AU - Lee, Chia AU - Yaeger, Daniel AU - Vyleta, Nicholas AU - Smith, Stephen ID - 3121 IS - 9 JF - Nature Neuroscience TI - Coactivation of multiple tightly coupled calcium channels triggers spontaneous release of GABA VL - 15 ER - TY - JOUR AB - The physical distance between presynaptic Ca2+ channels and the Ca2+ sensors that trigger exocytosis of neurotransmitter-containing vesicles is a key determinant of the signalling properties of synapses in the nervous system. Recent functional analysis indicates that in some fast central synapses, transmitter release is triggered by a small number of Ca2+ channels that are coupled to Ca2+ sensors at the nanometre scale. Molecular analysis suggests that this tight coupling is generated by protein–protein interactions involving Ca2+ channels, Ca2+ sensors and various other synaptic proteins. Nanodomain coupling has several functional advantages, as it increases the efficacy, speed and energy efficiency of synaptic transmission. AU - Eggermann, Emmanuel AU - Bucurenciu, Iancu AU - Goswami, Sarit AU - Jonas, Peter M ID - 3317 IS - 1 JF - Nature Reviews Neuroscience TI - Nanodomain coupling between Ca(2+) channels and sensors of exocytosis at fast mammalian synapses VL - 13 ER - TY - JOUR AB - The BCI competition IV stands in the tradition of prior BCI competitions that aim to provide high quality neuroscientific data for open access to the scientific community. As experienced already in prior competitions not only scientists from the narrow field of BCI compete, but scholars with a broad variety of backgrounds and nationalities. They include high specialists as well as students.The goals of all BCI competitions have always been to challenge with respect to novel paradigms and complex data. We report on the following challenges: (1) asynchronous data, (2) synthetic, (3) multi-class continuous data, (4) sessionto-session transfer, (5) directionally modulated MEG, (6) finger movements recorded by ECoG. As after past competitions, our hope is that winning entries may enhance the analysis methods of future BCIs. AU - Tangermann, Michael AU - Müller, Klaus AU - Aertsen, Ad AU - Birbaumer, Niels AU - Braun, Christoph AU - Brunner, Clemens AU - Leeb, Robert AU - Mehring, Carsten AU - Miller, Kai AU - Müller Putz, Gernot AU - Nolte, Guido AU - Pfurtscheller, Gert AU - Preissl, Hubert AU - Schalk, Gerwin AU - Schlögl, Alois AU - Vidaurre, Carmen AU - Waldert, Stephan AU - Blankertz, Benjamin ID - 493 JF - Frontiers in Neuroscience TI - Review of the BCI competition IV VL - 6 ER - TY - JOUR AB - CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+ channel–mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na+-to-K+ conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network. AU - Kim, Sooyun AU - Guzmán, José AU - Hu, Hua AU - Jonas, Peter M ID - 3258 IS - 4 JF - Nature Neuroscience SN - 1546-1726 TI - Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons VL - 15 ER - TY - THES AB - CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. These neurons receive multiple excitatory inputs from numerous sources. Therefore, the rules of spatiotemporal integration of multiple synaptic inputs and propagation of action potentials are important to understand how CA3 neurons contribute to higher brain functions at cellular level. By using confocally targeted patch-clamp recording techniques, we investigated the biophysical properties of rat CA3 pyramidal neuron dendrites. We found two distinct dendritic domains critical for action potential initiation and propagation: In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+-channel mediated dendritic spikes are efficiently evoked by local dendritic depolarization or waveforms mimicking synaptic events. These findings can be explained by a high Na+-to-K+ conductance density ratio of CA3 pyramidal neuron dendrites. The results challenge the prevailing view that proximal mossy fiber inputs activate CA3 pyramidal neurons more efficiently than distal perforant inputs by showing that the distal synapses trigger a different form of activity represented by dendritic spikes. The high probability of dendritic spike initiation in the distal area may enhance the computational power of CA3 pyramidal neurons in the hippocampal network. AU - Kim, Sooyun ID - 2964 SN - 2663-337X TI - Active properties of hippocampal CA3 pyramidal neuron dendrites ER - TY - JOUR AB - Parvalbumin is thought to act in a manner similar to EGTA, but how a slow Ca2+ buffer affects nanodomain-coupling regimes at GABAergic synapses is unclear. Direct measurements of parvalbumin concentration and paired recordings in rodent hippocampus and cerebellum revealed that parvalbumin affects synaptic dynamics only when expressed at high levels. Modeling suggests that, in high concentrations, parvalbumin may exert BAPTA-like effects, modulating nanodomain coupling via competition with local saturation of endogenous fixed buffers. AU - Eggermann, Emmanuel AU - Jonas, Peter M ID - 3318 JF - Nature Neuroscience TI - How the “slow” Ca(2+) buffer parvalbumin affects transmitter release in nanodomain coupling regimes at GABAergic synapses VL - 15 ER - TY - JOUR AB - Rab3 interacting molecules (RIMs) are highly enriched in the active zones of presynaptic terminals. It is generally thought that they operate as effectors of the small G protein Rab3. Three recent papers, by Han et al. (this issue of Neuron), Deng et al. (this issue of Neuron), and Kaeser et al. (a recent issue of Cell), shed new light on the functional role of RIM in presynaptic terminals. First, RIM tethers Ca2+ channels to active zones. Second, RIM contributes to priming of synaptic vesicles by interacting with another presynaptic protein, Munc13. AU - Pernia-Andrade, Alejandro AU - Jonas, Peter M ID - 3369 IS - 2 JF - Neuron TI - The multiple faces of RIM VL - 69 ER - TY - JOUR AB - Spontaneous release of glutamate is important for maintaining synaptic strength and controlling spike timing in the brain. Mechanisms regulating spontaneous exocytosis remain poorly understood. Extracellular calcium concentration ([Ca2+]o) regulates Ca2+ entry through voltage-activated calcium channels (VACCs) and consequently is a pivotal determinant of action potential-evoked vesicle fusion. Extracellular Ca 2+ also enhances spontaneous release, but via unknown mechanisms. Here we report that external Ca2+ triggers spontaneous glutamate release more weakly than evoked release in mouse neocortical neurons. Blockade of VACCs has no effect on the spontaneous release rate or its dependence on [Ca2+]o. Intracellular [Ca2+] slowly increases in a minority of neurons following increases in [Ca2+]o. Furthermore, the enhancement of spontaneous release by extracellular calcium is insensitive to chelation of intracellular calcium by BAPTA. Activation of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor present in nerve terminals, by several specific agonists increased spontaneous glutamate release. The frequency of spontaneous synaptic transmission was decreased in CaSR mutant neurons. The concentration-effect relationship for extracellular calcium regulation of spontaneous release was well described by a combination of CaSR-dependent and CaSR-independent mechanisms. Overall these results indicate that extracellular Ca2+ does not trigger spontaneous glutamate release by simply increasing calcium influx but stimulates CaSR and thereby promotes resting spontaneous glutamate release. AU - Vyleta, Nicholas AU - Smith, Stephen ID - 469 IS - 12 JF - European Journal of Neuroscience TI - Spontaneous glutamate release is independent of calcium influx and tonically activated by the calcium-sensing receptor VL - 31 ER - TY - JOUR AB - BioSig is an open source software library for biomedical signal processing. The aim of the BioSig project is to foster research in biomedical signal processing by providing free and open source software tools for many different application areas. Some of the areas where BioSig can be employed are neuroinformatics, brain-computer interfaces, neurophysiology, psychology, cardiovascular systems, and sleep research. Moreover, the analysis of biosignals such as the electroencephalogram (EEG), electrocorticogram (ECoG), electrocardiogram (ECG), electrooculogram (EOG), electromyogram (EMG), or respiration signals is a very relevant element of the BioSig project. Specifically, BioSig provides solutions for data acquisition, artifact processing, quality control, feature extraction, classification, modeling, and data visualization, to name a few. In this paper, we highlight several methods to help students and researchers to work more efficiently with biomedical signals. AU - Schlögl, Alois AU - Vidaurre, Carmen AU - Sander, Tilmann ID - 490 JF - Computational Intelligence and Neuroscience TI - BioSig: The free and open source software library for biomedical signal processing VL - 2011 ER - TY - JOUR AB - Long-term depression (LTD) is a form of synaptic plasticity that may contribute to information storage in the central nervous system. Here we report that LTD can be elicited in layer 5 pyramidal neurons of the rat prefrontal cortex by pairing low frequency stimulation with a modest postsynaptic depolarization. The induction of LTD required the activation of both metabotropic glutamate receptors of the mGlu1 subtype and voltage-sensitive Ca(2+) channels (VSCCs) of the T/R, P/Q and N types, leading to the stimulation of intracellular inositol trisphosphate (IP3) receptors by IP3 and Ca(2+). The subsequent release of Ca(2+) from intracellular stores activated the protein phosphatase cascade involving calcineurin and protein phosphatase 1. The activation of purinergic P2Y(1) receptors blocked LTD. This effect was prevented by P2Y(1) receptor antagonists and was absent in mice lacking P2Y(1) but not P2Y(2) receptors. We also found that activation of P2Y(1) receptors inhibits Ca(2+) transients via VSCCs in the apical dendrites and spines of pyramidal neurons. In addition, we show that the release of ATP under hypoxia is able to inhibit LTD by acting on postsynaptic P2Y(1) receptors. In conclusion, these data suggest that the reduction of Ca(2+) influx via VSCCs caused by the activation of P2Y(1) receptors by ATP is the possible mechanism for the inhibition of LTD in prefrontal cortex. AU - Guzmán, José AU - Schmidt, Hartmut AU - Franke, Heike AU - Krügel, Ute AU - Eilers, Jens AU - Illes, Peter AU - Gerevich, Zoltan ID - 3718 IS - 6 JF - Neuropharmacology TI - P2Y1 receptors inhibit long-term depression in the prefrontal cortex. VL - 59 ER - TY - JOUR AB - A recent paper by von Engelhardt et al. identifies a novel auxiliary subunit of native AMPARs, termedCKAMP44. Unlike other auxiliary subunits, CKAMP44 accelerates desensitization and prolongs recovery from desensitization. CKAMP44 is highly expressed in hippocampal dentate gyrus granule cells and decreases the paired-pulse ratio at perforant path input synapses. Thus, both principal and auxiliary AMPAR subunits control the time course of signaling at glutamatergic synapses. AU - Guzmán, José AU - Jonas, Peter M ID - 3832 IS - 1 JF - Neuron TI - Beyond TARPs: The growing list of auxiliary AMPAR subunits VL - 66 ER - TY - JOUR AU - Jonas, Peter M AU - Hefft, Stefan ID - 3833 IS - 7 JF - The European Journal of Neuroscience TI - GABA release at terminals of CCK-interneurons: synchrony, asynchrony and modulation by cannabinoid receptors (commentary on Ali & Todorova) VL - 31 ER -