25 results on '"Volker Scheuss"'
Search Results
2. Quantitative Analysis of the Spatial Organization of Synaptic Inputs on the Postsynaptic Dendrite
- Author
-
Volker Scheuss
- Subjects
synaptic input ,dendritic integration ,dendrite ,spatial organization ,synapse cluster ,quantitative analysis ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The spatial organization of synaptic inputs on the dendritic tree of cortical neurons is considered to play an important role in the dendritic integration of synaptic activity. Active electrical properties of dendrites and mechanisms of dendritic integration have been studied for a long time. New technological developments are now enabling the characterization of the spatial organization of synaptic inputs on dendrites. However, quantitative methods for the analysis of such data are lacking. In order to place cluster parameters into the framework of dendritic integration and synaptic summation, these parameters need to be assessed rigorously in a quantitative manner. Here I present an approach for the analysis of synaptic input clusters on the dendritic tree that is based on combinatorial analysis of the likelihoods to observe specific input arrangements. This approach is superior to the commonly applied analysis of nearest neighbor distances between synaptic inputs comparing their distribution to simulations with random reshuffling or bootstrapping. First, the new approach yields exact likelihood values rather than approximate numbers obtained from simulations. Second and more importantly, the new approach identifies individual clusters and thereby allows to quantify and characterize individual cluster properties.
- Published
- 2018
- Full Text
- View/download PDF
3. Clusters of synaptic inputs on dendrites of layer 5 pyramidal cells in mouse visual cortex
- Author
-
Onur Gökçe, Tobias Bonhoeffer, and Volker Scheuss
- Subjects
synapse mapping ,synapse cluster ,optogenetics ,2-photon calcium imaging ,visual cortex ,spatial cluster analysis ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
The spatial organization of synaptic inputs on the dendritic tree of cortical neurons plays a major role for dendritic integration and neural computations, yet, remarkably little is known about it. We mapped the spatial organization of glutamatergic synapses between layer 5 pyramidal cells by combining optogenetics and 2-photon calcium imaging in mouse neocortical slices. To mathematically characterize the organization of inputs we developed an approach based on combinatorial analysis of the likelihoods of specific synapse arrangements. We found that the synapses of intralaminar inputs form clusters on the basal dendrites of layer 5 pyramidal cells. These clusters contain 4 to 14 synapses within ≤30 µm of dendrite. According to the spatiotemporal characteristics of synaptic summation, these numbers suggest that there will be non-linear dendritic integration of synaptic inputs during synchronous activation.
- Published
- 2016
- Full Text
- View/download PDF
4. Characterization and subcellular targeting of GCaMP-type genetically-encoded calcium indicators.
- Author
-
Tianyi Mao, Daniel H O'Connor, Volker Scheuss, Junichi Nakai, and Karel Svoboda
- Subjects
Medicine ,Science - Abstract
Genetically-encoded calcium indicators (GECIs) hold the promise of monitoring [Ca(2+)] in selected populations of neurons and in specific cellular compartments. Relating GECI fluorescence to neuronal activity requires quantitative characterization. We have characterized a promising new genetically-encoded calcium indicator-GCaMP2-in mammalian pyramidal neurons. Fluorescence changes in response to single action potentials (17+/-10% DeltaF/F [mean+/-SD]) could be detected in some, but not all, neurons. Trains of high-frequency action potentials yielded robust responses (302+/-50% for trains of 40 action potentials at 83 Hz). Responses were similar in acute brain slices from in utero electroporated mice, indicating that long-term expression did not interfere with GCaMP2 function. Membrane-targeted versions of GCaMP2 did not yield larger signals than their non-targeted counterparts. We further targeted GCaMP2 to dendritic spines to monitor Ca(2+) accumulations evoked by activation of synaptic NMDA receptors. We observed robust DeltaF/F responses (range: 37%-264%) to single spine uncaging stimuli that were correlated with NMDA receptor currents measured through a somatic patch pipette. One major drawback of GCaMP2 was its low baseline fluorescence. Our results show that GCaMP2 is improved from the previous versions of GCaMP and may be suited to detect bursts of high-frequency action potentials and synaptic currents in vivo.
- Published
- 2008
- Full Text
- View/download PDF
5. Functional and structural features of L2/3 pyramidal cells continuously covary with pial depth in mouse visual cortex
- Author
-
Simon Weiler, Drago Guggiana Nilo, Tobias Bonhoeffer, Mark Hübener, Tobias Rose, and Volker Scheuss
- Subjects
Cellular and Molecular Neuroscience ,Cognitive Neuroscience - Abstract
Pyramidal cells of neocortical layer 2/3 (L2/3 PyrCs) integrate signals from numerous brain areas and project throughout the neocortex. These PyrCs show pial depth-dependent functional and structural specializations, indicating participation in different functional microcircuits. However, whether these depth-dependent differences result from separable PyrC subtypes or whether their features display a continuum correlated with pial depth is unknown. Here, we assessed the stimulus selectivity, electrophysiological properties, dendritic morphology, and excitatory and inhibitory connectivity across the depth of L2/3 in the binocular visual cortex of mice. We find that the apical, but not the basal dendritic tree structure, varies with pial depth, which is accompanied by variation in subthreshold electrophysiological properties. Lower L2/3 PyrCs receive increased input from L4, while upper L2/3 PyrCs receive a larger proportion of intralaminar input. In vivo calcium imaging revealed a systematic change in visual responsiveness, with deeper PyrCs showing more robust responses than superficial PyrCs. Furthermore, deeper PyrCs are more driven by contralateral than ipsilateral eye stimulation. Importantly, the property value transitions are gradual, and L2/3 PyrCs do not display discrete subtypes based on these parameters. Therefore, L2/3 PyrCs’ multiple functional and structural properties systematically correlate with their depth, forming a continuum rather than discrete subtypes.
- Published
- 2022
6. Functional and structural features of L2/3 pyramidal cells continuously covary with pial depth in mouse visual cortex
- Author
-
D. G. Nilo, Volker Scheuss, S. Weiler, Tobias Rose, Tobias Bonhoeffer, and M. H uumlbener
- Subjects
Electrophysiology ,Visual cortex ,medicine.anatomical_structure ,Calcium imaging ,Neocortex ,Chemistry ,Excitatory postsynaptic potential ,medicine ,Stimulation ,Stimulus (physiology) ,Inhibitory postsynaptic potential ,Neuroscience - Abstract
Pyramidal cells of neocortical layer 2/3 (L2/3 PyrCs) integrate signals from numerous brain areas and project throughout the neocortex. Within L2/3, PyrCs show functional and structural specializations depending on their pial depth, indicating participation in different functional microcircuits. However, it is unknown whether these depth-dependent differences result from separable L2/3 PyrC subtypes or whether functional and structural features represent a continuum while correlating with pial depth. Here, we assessed the stimulus selectivity, electrophysiological properties, dendritic morphology, and excitatory and inhibitory synaptic connectivity across the depth of L2/3 in the binocular visual cortex (bV1) of female mice. We find that the structure of the apical but not the basal dendritic tree varies with pial depth, which is accompanied by differences in passive but not active electrophysiological properties. PyrCs in lower L2/3 receive increased excitatory and inhibitory input from L4, while upper L2/3 PyrCs receive a larger proportion of intralaminar input. Complementary in vivo calcium imaging revealed a systematic change in visual responsiveness, with deeper L2/3 PyrCs showing more robust responses than superficial PyrCs. Furthermore, deeper L2/3 PyrCs are more strongly driven by contralateral than ipsilateral eye stimulation. In contrast, orientation- and direction-selectivity of L2/3 PyrCs are not dependent on pial depth. Importantly, the transitions of the various properties are gradual, and cluster analysis does not support the classification of L2/3 PyrCs into discrete subtypes. These results show that L2/3 PyrCs’ multiple functional and structural properties systematically correlate with their depth within L2/3, forming a continuum rather than representing discrete subtypes.SIGNIFICANCE STATEMENTNeocortical pyramidal cells in layer 2/3 (L2/3 PyrCs) are crucial for cortical computation and display heterogenous properties. We investigated whether and how these properties vary across the depth of L2/3 and whether L2/3 PyrCs can be subdivided into distinct subtypes. This is important for a better understanding of the coding strategy and information integration processes within L2/3. We find that multiple properties such as morphology, physiology, connectivity, and functional in vivo responses of L2/3 PyrCs correlate with cortical depth in mouse visual cortex. These variations are continuous and do not support classification of L2/3 PyrCs into discrete subtypes. In contrast to L5 and L6, PyrCs in L2/3 therefore process information based on a continuous property space.
- Published
- 2021
7. Limited functional convergence of eye-specific inputs in the retinogeniculate pathway of the mouse
- Author
-
Martin H.P. Fernholz, Joel Bauer, Volker Scheuss, Simon Weiler, Mark Hübener, Tobias Rose, Tobias Bonhoeffer, and David Laubender
- Subjects
0301 basic medicine ,Retinal Ganglion Cells ,genetic structures ,Biology ,Optogenetics ,Lateral geniculate nucleus ,Functional Laterality ,Ocular dominance ,Synapse ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Animals ,Visual Pathways ,Vision, Binocular ,General Neuroscience ,Geniculate Bodies ,eye diseases ,Monocular deprivation ,030104 developmental biology ,medicine.anatomical_structure ,Visual cortex ,nervous system ,Retinal ganglion cell ,sense organs ,Neuron ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Summary Segregation of retinal ganglion cell (RGC) axons by type and eye of origin is considered a hallmark of dorsal lateral geniculate nucleus (dLGN) structure. However, recent anatomical studies have shown that neurons in mouse dLGN receive input from multiple RGC types of both retinae. Whether convergent input leads to relevant functional interactions is unclear. We studied functional eye-specific retinogeniculate convergence using dual-color optogenetics in vitro. dLGN neurons were strongly dominated by input from one eye. Most neurons received detectable input from the non-dominant eye, but this input was weak, with a prominently reduced AMPAR:NMDAR ratio. Consistent with this, only a small fraction of thalamocortical neurons was binocular in vivo across visual stimuli and cortical projection layers. Anatomical overlap between RGC axons and dLGN neuron dendrites alone did not explain the strong bias toward monocularity. We conclude that functional eye-specific input selection and refinement limit convergent interactions in dLGN, favoring monocularity.
- Published
- 2020
8. Orientation and direction tuning align with dendritic morphology and spatial connectivity in mouse visual cortex
- Author
-
Simon Weiler, Drago Guggiana Nilo, Tobias Bonhoeffer, Mark Hübener, Tobias Rose, and Volker Scheuss
- Subjects
Neurons ,Mice ,Pyramidal Cells ,Animals ,Neural Inhibition ,Dendrites ,General Agricultural and Biological Sciences ,General Biochemistry, Genetics and Molecular Biology ,Visual Cortex - Abstract
Summary The functional properties of neocortical pyramidal cells (PCs), such as direction and orientation selectivity in visual cortex, predominantly derive from their excitatory and inhibitory inputs. For layer 2/3 (L2/3) PCs, the detailed relationship between their functional properties and how they sample and integrate information across cortical space is not fully understood. Here, we study this relationship by combining functional in vivo two-photon calcium imaging, in vitro functional circuit mapping, and dendritic reconstruction of the same L2/3 PCs in mouse visual cortex. Our work reveals direct correlations between dendritic morphology and functional input connectivity and the orientation as well as direction tuning of L2/3 PCs. First, the apical dendritic tree is elongated along the postsynaptic preferred orientation, considering the representation of visual space in the cortex as determined by its retinotopic organization. Additionally, sharply orientation-tuned cells show a less complex apical tree compared with broadly tuned cells. Second, in direction-selective L2/3 PCs, the spatial distribution of presynaptic partners is offset from the soma opposite to the preferred direction. Importantly, although the presynaptic excitatory and inhibitory input distributions spatially overlap on average, the excitatory input distribution is spatially skewed along the preferred direction, in contrast to the inhibitory distribution. Finally, the degree of asymmetry is positively correlated with the direction selectivity of the postsynaptic L2/3 PC. These results show that the dendritic architecture and the spatial arrangement of excitatory and inhibitory presynaptic cells of L2/3 PCs play important roles in shaping their orientation and direction tuning.
- Published
- 2022
9. Selective connectivity limits functional binocularity in the retinogeniculate pathway of the mouse
- Author
-
Simon Weiler, Tobias Rose, Mark Hübener, Joel Bauer, Martin H.P. Fernholz, Tobias Bonhoeffer, Volker Scheuss, and David Laubender
- Subjects
System development ,genetic structures ,Dorsal lateral geniculate nucleus ,Optogenetics ,Biology ,eye diseases ,medicine.anatomical_structure ,Retinal ganglion cell ,medicine ,sense organs ,Neuron ,Input selection ,Neuroscience ,Binocular vision - Abstract
Eye-specific segregation of retinal ganglion cell (RGC) axons in the dorsal lateral geniculate nucleus (dLGN) is considered a hallmark of visual system development. However, a recent anatomical study showed that nearly half of the neurons in dLGN of adult mice still receive input from both retinae, but functional data about binocularity in mature dLGN is conflicting. Here, we found that a variable but small fraction of thalamocortical neurons is binocular in vivo. Using dual-channel optogenetics in vitro we correspondingly found that dLGN neurons are dominated by retinogeniculate input from one eye only, although most neurons also received small but detectable input from the non-dominant eye. Anatomical overlap between RGC axons and dLGN neuron dendrites did not explain this strong bias towards monocularity. Our data rather suggest that functional input selection and refinement, leaving the remaining non-dominant eye inputs in a juvenile-like state, underlies the prevalent monocularity of neurons in dLGN.
- Published
- 2020
10. Inducing different neuronal subtypes from astrocytes in the injured mouse cerebral cortex
- Author
-
Nicola Mattugini, Volker Scheuss, Chu Lan Lao, Olof Torper, Magdalena Götz, Riccardo Bocchi, and Gianluca Luigi Russo
- Subjects
0301 basic medicine ,Genetic Vectors ,Inflammation ,Nerve Tissue Proteins ,Wounds, Stab ,Biology ,Article ,White matter ,03 medical and health sciences ,Mice ,reactive gliosis ,Aav ,Astrocytes ,Axonal Projection ,Cerebral Cortex ,Cortical Layers ,Electrophysiology ,Lentivirus ,Reactive Gliosis ,Reprogramming ,0302 clinical medicine ,lentivirus ,Brain Injuries, Traumatic ,Nuclear Receptor Subfamily 4, Group A, Member 2 ,medicine ,Basic Helix-Loop-Helix Transcription Factors ,Animals ,Cellular Reprogramming Techniques ,Neurogenin-2 ,Gliosis ,Gray Matter ,Neurons ,General Neuroscience ,Pyramidal Cells ,astrocytes ,reprogramming ,AAV ,cortical layers ,Dependovirus ,electrophysiology ,White Matter ,030104 developmental biology ,medicine.anatomical_structure ,Cerebral cortex ,inflammation ,Mouse Cerebral Cortex ,medicine.symptom ,axonal projection ,Neuroscience ,030217 neurology & neurosurgery ,Astrocyte - Abstract
Summary Astrocytes are particularly promising candidates for reprogramming into neurons, as they maintain some of the original patterning information from their radial glial ancestors. However, to which extent the position of astrocytes influences the fate of reprogrammed neurons remains unknown. To elucidate this, we performed stab wound injury covering an entire neocortical column, including the gray matter (GM) and white matter (WM), and targeted local reactive astrocytes via injecting FLEx switch (Cre-On) adeno-associated viral (AAV) vectors into mGFAP-Cre mice. Single proneural factors were not sufficient for adequate reprogramming, although their combination with the nuclear receptor-related 1 protein (Nurr1) improved reprogramming efficiency. Nurr1 and Neurogenin 2 (Ngn2) resulted in high-efficiency reprogramming of targeted astrocytes into neurons that develop lamina-specific hallmarks, including the appropriate long-distance axonal projections. Surprisingly, in the WM, we did not observe any reprogrammed neurons, thereby unveiling a crucial role of region- and layer-specific differences in astrocyte reprogramming., Graphical Abstract, Highlights • AAV can be targeted to reactive astrocytes upon stab wound injury • Expression of Ngn2 and Nurr1 in these astrocytes induces pyramidal neurons • Induced pyramidal neurons acquire correct layer identity and axonal projections • Neurons cannot be induced in the white matter, Neurons dying after brain injury cannot be replaced. Mattugini, Bocchi, et al. show that local astrocytes can be converted into functional neurons acquiring appropriate layer identity and connectivity by expression of neurogenic factors in a mouse model of traumatic brain injury.
- Published
- 2019
11. Function of Dendritic Spines on Hippocampal Inhibitory Neurons
- Author
-
Volker Scheuss and Tobias Bonhoeffer
- Subjects
musculoskeletal diseases ,Patch-Clamp Techniques ,Dendritic spine ,Interneuron ,Dendritic Spines ,Cognitive Neuroscience ,Action Potentials ,Mice, Transgenic ,Nerve Tissue Proteins ,In Vitro Techniques ,Biology ,Inhibitory postsynaptic potential ,Hippocampus ,Mice ,Cellular and Molecular Neuroscience ,Interneurons ,medicine ,Animals ,gamma-Aminobutyric Acid ,Neurotransmitter Agents ,Dendritic spike ,Neuronal Plasticity ,Glutamate Decarboxylase ,Pyramidal Cells ,Neuropeptides ,Age Factors ,Dendritic filopodia ,Mice, Inbred C57BL ,Spine (zoology) ,medicine.anatomical_structure ,Inhibitory Postsynaptic Potentials ,Receptors, Glutamate ,nervous system ,Synapses ,GABAergic ,Pyramidal cell ,Neuroscience - Abstract
The majority of γ-aminobutyric acid (GABA)ergic interneurons have smooth dendrites with no or only few dendritic spines, but certain types of spiny GABAergic interneurons do actually contain substantial numbers of spines. The explanation for such spines has so far been purely structural: They increase the dendritic surface area and thus provide the opportunity to accommodate larger numbers of synapses. We reasoned that there may be specific functional properties for these spines and therefore, undertook to characterize interneuron spines functionally. We find a remarkable similarity to pyramidal cell spines: They receive excitatory synapses with calcium impermeable α-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors, compartmentalize biochemical signals, and display activity-dependent morphological plasticity. Nevertheless, notable differences in spine density, neck length, and spine-dendrite coupling exist. Thus, dendritic spines on inhibitory interneurons have a number of important functional properties that go substantially beyond simply expanding the dendritic surface area. It therefore seems likely that spiny and aspiny interneurons may have very different roles in neural circuit function and plasticity.
- Published
- 2013
12. Author response: Clusters of synaptic inputs on dendrites of layer 5 pyramidal cells in mouse visual cortex
- Author
-
Tobias Bonhoeffer, Volker Scheuss, and Onur Gökçe
- Subjects
0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,Visual cortex ,medicine.anatomical_structure ,Chemistry ,medicine ,Layer (electronics) ,Neuroscience - Published
- 2016
13. Kinetics of both synchronous and asynchronous quantal release during trains of action potential-evoked EPSCs at the rat calyx of Held
- Author
-
Erwin Neher, Holger Taschenberger, and Volker Scheuss
- Subjects
Synapse ,Physiology ,Chemistry ,Postsynaptic Current ,Postsynaptic potential ,Excitatory postsynaptic potential ,Time constant ,Biophysics ,Stimulus (physiology) ,Summation ,Calyx of Held ,Neuroscience - Abstract
We studied the kinetics of transmitter release during trains of action potential (AP)-evoked excitatory postsynaptic currents (EPSCs) at the calyx of Held synapse of juvenile rats. Using a new quantitative method based on a combination of ensemble fluctuation analysis and deconvolution, we were able to analyse mean quantal size (q) and release rate (ξ) continuously in a time-resolved manner. Estimates derived this way agreed well with values of q and quantal content (M) calculated for each EPSC within the train from ensemble means of peak amplitudes and their variances. Separate analysis of synchronous and asynchronous quantal release during long stimulus trains (200 ms, 100 Hz) revealed that the latter component was highly variable among different synapses but it was unequivocally identified in 18 out of 37 synapses analysed. Peak rates of asynchronous release ranged from 0.2 to 15.2 vesicles ms−1 (ves ms−1) with a mean of 2.3 ± 0.6 ves ms−1. On average, asynchronous release accounted for less than 14% of the total number of about 3670 ± 350 vesicles released during 200 ms trains. Following such trains, asynchronous release decayed with several time constants, the fastest one being in the order of 15 ms. The short duration of asynchronous release at the calyx of Held synapse may aid in generating brief postsynaptic depolarizations, avoiding temporal summation and preserving action potential timing during high frequency bursts.
- Published
- 2007
14. Release kinetics, quantal parameters and their modulation during short-term depression at a developing synapse in the rat CNS
- Author
-
Volker Scheuss, Erwin Neher, and Holger Taschenberger
- Subjects
Synapse ,chemistry.chemical_compound ,Desensitization (telecommunications) ,chemistry ,Physiology ,Excitatory postsynaptic potential ,Biophysics ,Glutamate receptor ,Stimulation ,Active zone ,Neurotransmitter ,Calyx of Held ,Neuroscience - Abstract
We have characterized developmental changes in the kinetics and quantal parameters of action potential (AP)-evoked neurotransmitter release during maturation of the calyx of Held synapse. Quantal size (q) and peak amplitudes of evoked EPSCs increased moderately, whereas the fraction of vesicles released by single APs decreased. During synaptic depression induced in postnatal day (P) 5–7 synapses by 10–100 Hz stimulation, q declined rapidly to 40–12% of its initial value. The decrease in q was generally smaller in more mature synapses (P12–14), but quite severe for frequencies ≥ 300 Hz. The stronger decline of q in immature synapses resulted from a slower recovery from desensitization, presumably due to delayed glutamate clearance. Recovery from this desensitization followed an exponential time course with a time constant of ∼480 ms in P5–7 synapses, and sped up > 20-fold during maturation. Deconvolution analysis of EPSCs revealed a significant acceleration of the release time course during development, which was accompanied by a 2-fold increase of the peak release rate. During long 100 Hz trains, more mature synapses were able to sustain average rates of 8–10 quanta s−1 per active zone for phasic release. The rates of asynchronous vesicle release increased transiently > 35-fold immediately after such stimuli and decayed rapidly with an exponential time constant of ∼50 ms to low resting levels of spontaneous release. However, even following extended periods of 100 Hz stimulation, the amount of asynchronous release was relatively minor with peak rates of less than 5% of the average rate of synchronous release measured at steady state during the tetani. Therefore, a multitude of mechanisms seems to converge on the generation of fast, temporally precise and reliable high-frequency transmission at the mature calyx of Held synapse.
- Published
- 2005
15. NMDA Receptor Subunit-Dependent [Ca2+] Signaling in Individual Hippocampal Dendritic Spines
- Author
-
Karel Svoboda, Volker Scheuss, and Aleksander Sobczyk
- Subjects
musculoskeletal diseases ,Dendritic spine ,Dendritic Spines ,General Neuroscience ,Protein subunit ,Glutamate receptor ,Hippocampal formation ,Biology ,Hippocampus ,Receptors, N-Methyl-D-Aspartate ,Spine (zoology) ,Electrophysiology ,nervous system ,Quinoxalines ,Synapses ,Biophysics ,Animals ,NMDA receptor ,Calcium Signaling ,Receptor ,Evoked Potentials ,Excitatory Amino Acid Antagonists ,Neuroscience ,Cellular/Molecular - Abstract
Ca2+influx through synaptic NMDA receptors (NMDA-Rs) triggers a variety of adaptive cellular processes. To probe NMDA-R-mediated [Ca2+] signaling, we used two-photon glutamate uncaging to stimulate NMDA-Rs on individual dendritic spines of CA1 pyramidal neurons in rat brain slices. We measured NMDA-R currents at the soma and NMDA-R-mediated [Ca2+] transients in stimulated spines (Δ[Ca2+]). Uncaging-evoked NMDA-R current amplitudes were independent of the size of the stimulated spine, implying that smaller spines contain higher densities of functional NMDA-Rs. The ratio of Δ[Ca2+] over NMDA-R current was highly variable (factor of 10) across spines, especially for small spines. These differences were not explained by heterogeneity in spine sizes or diffusional coupling between spines and their parent dendrites. In addition, we find that small spines have NMDA-R currents that are sensitive to NMDA-R NR2B subunit-specific antagonists. With block of NR2B-containing receptors, the range of Δ[Ca2+]/NMDA-R current ratios and their average value were much reduced. Our data suggest that individual spines can regulate the subunit composition of their NMDA-Rs and the effective fractional Ca2+current through these receptors.
- Published
- 2005
16. Balance and stability of synaptic structures during synaptic plasticity
- Author
-
Tobias Bonhoeffer, Daniel Meyer, and Volker Scheuss
- Subjects
musculoskeletal diseases ,Dendritic spine ,Time Factors ,Neuroscience(all) ,Dendritic Spines ,Green Fluorescent Proteins ,Glutamic Acid ,Biology ,Synapse ,Organ Culture Techniques ,Homer Scaffolding Proteins ,Transduction, Genetic ,Synaptic augmentation ,mental disorders ,Animals ,Active zone ,Rats, Wistar ,CA1 Region, Hippocampal ,Neurons ,Neuronal Plasticity ,musculoskeletal, neural, and ocular physiology ,General Neuroscience ,Intracellular Signaling Peptides and Proteins ,Membrane Proteins ,Post-Synaptic Density ,Long-term potentiation ,Rats ,nervous system ,Animals, Newborn ,Disks Large Homolog 4 Protein ,Synaptic plasticity ,Synapses ,Plant Lectins ,Carrier Proteins ,Postsynaptic density ,Neuroscience ,psychological phenomena and processes - Abstract
SummarySubsynaptic structures such as bouton, active zone, postsynaptic density (PSD) and dendritic spine, are highly correlated in their dimensions and also correlate with synapse strength. Why this is so and how such correlations are maintained during synaptic plasticity remains poorly understood. We induced spine enlargement by two-photon glutamate uncaging and examined the relationship between spine, PSD, and bouton size by two-photon time-lapse imaging and electron microscopy. In enlarged spines the PSD-associated protein Homer1c increased rapidly, whereas the PSD protein PSD-95 increased with a delay and only in cases of persistent spine enlargement. In the case of nonpersistent spine enlargement, the PSD proteins remained unchanged or returned to their original level. The ultrastructure at persistently enlarged spines displayed matching dimensions of spine, PSD, and bouton, indicating their correlated enlargement. This supports a model in which balancing of synaptic structures is a hallmark for the stabilization of structural modifications during synaptic plasticity.
- Published
- 2014
17. Estimating Synaptic Parameters from Mean, Variance, and Covariance in Trains of Synaptic Responses
- Author
-
Erwin Neher and Volker Scheuss
- Subjects
Sequence ,Analysis of Variance ,Models, Statistical ,Basis (linear algebra) ,Quantitative Biology::Neurons and Cognition ,Monte Carlo method ,Models, Neurological ,Statistics as Topic ,Biophysics ,Covariance ,Neurotransmission ,Synaptic Transmission ,Binomial distribution ,Kinetics ,Amplitude ,Analysis of variance ,Biological system ,Mathematics ,Probability ,Research Article - Abstract
Fluctuation analysis of synaptic transmission using the variance–mean approach has been restricted in the past to steady-state responses. Here we extend this method to short repetitive trains of synaptic responses, during which the response amplitudes are not stationary. We consider intervals between trains, long enough so that the system is in the same average state at the beginning of each train. This allows analysis of ensemble means and variances for each response in a train separately. Thus, modifications in synaptic efficacy during short-term plasticity can be attributed to changes in synaptic parameters. In addition, we provide practical guidelines for the analysis of the covariance between successive responses in trains. Explicit algorithms to estimate synaptic parameters are derived and tested by Monte Carlo simulations on the basis of a binomial model of synaptic transmission, allowing for quantal variability, heterogeneity in the release probability, and postsynaptic receptor saturation and desensitization. We find that the combined analysis of variance and covariance is advantageous in yielding an estimate for the number of release sites, which is independent of heterogeneity in the release probability under certain conditions. Furthermore, it allows one to calculate the apparent quantal size for each response in a sequence of stimuli.
- Published
- 2001
- Full Text
- View/download PDF
18. Functional Interaction of the Active Zone Proteins Munc13-1 and RIM1 in Synaptic Vesicle Priming
- Author
-
Harald J. Junge, Jens Rettig, Uri Ashery, Andrea Betz, Pratima Thakur, Nils Brose, Volker Scheuss, Christian Rosenmund, and Jeong-Seop Rhee
- Subjects
Vesicle fusion ,Neuroscience(all) ,Molecular Sequence Data ,Presynaptic Terminals ,Nerve Tissue Proteins ,Biology ,Synaptic Transmission ,Synaptic vesicle ,Vesicle tethering ,Fungal Proteins ,Two-Hybrid System Techniques ,Synaptic augmentation ,Animals ,Protein Isoforms ,Cells, Cultured ,Neurons ,Neurotransmitter Agents ,Binding Sites ,Sequence Homology, Amino Acid ,General Neuroscience ,SNAP25 ,Zinc Fingers ,Munc-18 ,Kiss-and-run fusion ,rab3A GTP-Binding Protein ,Protein Structure, Tertiary ,Cell biology ,DNA-Binding Proteins ,Alternative Splicing ,Synaptic Vesicles ,Synaptic vesicle priming - Abstract
Synaptic neurotransmitter release is restricted to active zones, where the processes of synaptic vesicle tethering, priming to fusion competence, and Ca2+-triggered fusion are taking place in a highly coordinated manner. We show that the active zone components Munc13-1, an essential vesicle priming protein, and RIM1, a Rab3 effector with a putative role in vesicle tethering, interact functionally. Disruption of this interaction causes a loss of fusion-competent synaptic vesicles, creating a phenocopy of Munc13-1-deficient neurons. RIM1 binding and vesicle priming are mediated by two distinct structural modules of Munc13-1. The Munc13-1/RIM1 interaction may create a functional link between synaptic vesicle tethering and priming, or it may regulate the priming reaction itself, thereby determining the number of fusion-competent vesicles.
- Published
- 2001
19. Syntaphilin
- Author
-
Jens Rettig, Qingning Su, Claudia Gerwin, Volker Scheuss, Sumiko Mochida, Zu-Hang Sheng, and Guifang Lao
- Subjects
Synaptobrevin ,General Neuroscience ,Neuroscience(all) ,Biology ,Neurotransmission ,Syntaxin 1 ,Cell biology ,Synaptic vesicle exocytosis ,chemistry.chemical_compound ,nervous system ,chemistry ,Syntaphilin ,Synaptic vesicle docking ,biological phenomena, cell phenomena, and immunity ,Neurotransmitter ,SNARE complex - Abstract
Syntaxin-1 is a key component of the synaptic vesicle docking/fusion machinery that forms the SNARE complex with VAMP/synaptobrevin and SNAP-25. Identifying proteins that modulate SNARE complex formation is critical for understanding the molecular mechanisms underlying neurotransmitter release and its modulation. We have cloned and characterized a protein called syntaphilin that is selectively expressed in brain. Syntaphilin competes with SNAP-25 for binding to syntaxin-1 and inhibits SNARE complex formation by absorbing free syntaxin-1. Transient overexpression of syntaphilin in cultured hippocampal neurons significantly reduces neurotransmitter release. Furthermore, introduction of syntaphilin into presynaptic superior cervical ganglion neurons in culture inhibits synaptic transmission. These findings suggest that syntaphilin may function as a molecular clamp that controls free syntaxin-1 availability for the assembly of the SNARE complex, and thereby regulates synaptic vesicle exocytosis.
- Published
- 2000
- Full Text
- View/download PDF
20. A presynaptic role for the ADP ribosylation factor (ARF)-specific GDP/GTP exchange factor msec7-1
- Author
-
Nils Brose, Volker Scheuss, Jens Rettig, Henriette Koch, and Uri Ashery
- Subjects
Embryo, Nonmammalian ,ADP ribosylation factor ,Recombinant Fusion Proteins ,Xenopus ,Green Fluorescent Proteins ,Neuromuscular Junction ,Small G Protein ,Neurotransmission ,Biology ,Kidney ,Transfection ,Exocytosis ,Neuromuscular junction ,Cell Line ,Cell membrane ,GTP-binding protein regulators ,GTP-Binding Proteins ,medicine ,Animals ,Guanine Nucleotide Exchange Factors ,Humans ,RNA, Messenger ,Cloning, Molecular ,Muscle, Skeletal ,Evoked Potentials ,Cells, Cultured ,Neurons ,Multidisciplinary ,ADP-Ribosylation Factors ,Cell Membrane ,Brain ,Proteins ,Biological Sciences ,Coculture Techniques ,Rats ,Cell biology ,Kinetics ,Luminescent Proteins ,medicine.anatomical_structure ,Synapses ,Guanine nucleotide exchange factor - Abstract
ADP ribosylation factors (ARFs) represent a family of small monomeric G proteins that switch from an inactive, GDP-bound state to an active, GTP-bound state. One member of this family, ARF6, translocates on activation from intracellular compartments to the plasma membrane and has been implicated in regulated exocytosis in neuroendocrine cells. Because GDP release in vivo is rather slow, ARF activation is facilitated by specific guanine nucleotide exchange factors like cytohesin-1 or ARNO. Here we show that msec7-1, a rat homologue of cytohesin-1, translocates ARF6 to the plasma membrane in living cells. Overexpression of msec7-1 leads to an increase in basal synaptic transmission at the Xenopus neuromuscular junction. msec7-1-containing synapses have a 5-fold higher frequency of spontaneous synaptic currents than control synapses. On stimulation, the amplitudes of the resulting evoked postsynaptic currents of msec7-1-overexpressing neurons are increased as well. However, further stimulation leads to a decline in amplitudes approaching the values of control synapses. This transient effect on amplitude is strongly reduced on overexpression of msec7-1E157K, a mutant incapable of translocating ARFs. Our results provide evidence that small G proteins of the ARF family and activating factors like msec7-1 play an important role in synaptic transmission, most likely by making more vesicles available for fusion at the plasma membrane.
- Published
- 1999
21. Loss of sensory input causes rapid structural changes of inhibitory neurons in adult mouse visual cortex
- Author
-
Volker Scheuss, Corette J. Wierenga, R. Irene Jacobsen, Ulf T. Eysel, Tara Keck, Tobias Bonhoeffer, and Mark Hübener
- Subjects
Diagnostic Imaging ,Dendritic spine ,Time Factors ,Sensory Receptor Cells ,Neuroscience(all) ,Dendritic Spines ,Green Fluorescent Proteins ,Presynaptic Terminals ,Glutamic Acid ,Sensory system ,Mice, Transgenic ,Visual system ,Biology ,In Vitro Techniques ,Inhibitory postsynaptic potential ,Retina ,03 medical and health sciences ,Glutamatergic ,Mice ,0302 clinical medicine ,Animals ,Sensory deprivation ,Neuropeptide Y ,Visual Pathways ,gamma-Aminobutyric Acid ,030304 developmental biology ,Visual Cortex ,0303 health sciences ,Brain Mapping ,Glutamate Decarboxylase ,General Neuroscience ,Neural Inhibition ,nervous system ,Inhibitory Postsynaptic Potentials ,Vesicular Glutamate Transport Protein 1 ,Excitatory postsynaptic potential ,Sensory Deprivation ,Neuroscience ,030217 neurology & neurosurgery - Abstract
SummaryA fundamental property of neuronal circuits is the ability to adapt to altered sensory inputs. It is well established that the functional synaptic changes underlying this adaptation are reflected by structural modifications in excitatory neurons. In contrast, the degree to which structural plasticity in inhibitory neurons accompanies functional changes is less clear. Here, we use two-photon imaging to monitor the fine structure of inhibitory neurons in mouse visual cortex after deprivation induced by retinal lesions. We find that a subset of inhibitory neurons carry dendritic spines, which form glutamatergic synapses. Removal of visual input correlates with a rapid and lasting reduction in the number of inhibitory cell spines. Similar to the effects seen for dendritic spines, the number of inhibitory neuron boutons dropped sharply after retinal lesions. Together, these data suggest that structural changes in inhibitory neurons may precede structural changes in excitatory circuitry, which ultimately result in functional adaptation following sensory deprivation.
- Published
- 2011
22. Nonlinear [Ca2+] signaling in dendrites and spines caused by activity-dependent depression of Ca2+ extrusion
- Author
-
Ryohei Yasuda, Karel Svoboda, Volker Scheuss, and Aleksander Sobczyk
- Subjects
Dendritic spine ,Models, Neurological ,Biological Transport, Active ,Hippocampus ,Sodium-Calcium Exchanger ,Synapse ,Rats, Sprague-Dawley ,Calcium imaging ,Premovement neuronal activity ,Animals ,Computer Simulation ,Calcium Signaling ,Cells, Cultured ,Sodium-calcium exchanger ,Chemistry ,General Neuroscience ,Pyramidal Cells ,Long-term potentiation ,Dendrites ,Articles ,Rats ,Kinetics ,Nonlinear Dynamics ,Synaptic plasticity ,Biophysics ,Plasma membrane Ca2+ ATPase ,Calcium ,Neuroscience - Abstract
Spine Ca2+triggers the induction of synaptic plasticity and other adaptive neuronal responses. The amplitude and time course of Ca2+signals specify the activation of the signaling pathways that trigger different forms of plasticity such as long-term potentiation and depression. The shapes of Ca2+signals are determined by the dynamics of Ca2+sources, Ca2+buffers, and Ca2+extrusion mechanisms. Here we show in rat CA1 pyramidal neurons that plasma membrane Ca2+pumps (PMCAs) and Na+/Ca2+exchangers are the major Ca2+extrusion pathways in spines and small dendrites. Surprisingly, we found that Ca2+extrusion via PMCA and Na+/Ca2+exchangers slows in an activity-dependent manner, mediated by intracellular Na+and Ca2+accumulations. This activity-dependent depression of Ca2+extrusion is, in part, attributable to Ca2+-dependent inactivation of PMCAs. Ca2+extrusion recovers from depression with a time constant of ∼0.5 s. Depression of Ca2+extrusion provides a positive feedback loop, converting small differences in stimuli into large differences in Ca2+concentration. Depression of Ca2+extrusion produces Ca2+concentration dynamics that depend on the history of neuronal activity and therefore likely modulates the induction of synaptic plasticity.
- Published
- 2006
23. Release kinetics, quantal parameters and their modulation during short-term depression at a developing synapse in the rat CNS
- Author
-
Holger, Taschenberger, Volker, Scheuss, and Erwin, Neher
- Subjects
Cell Physiology ,N-Methylaspartate ,Presynaptic Terminals ,Action Potentials ,Excitatory Postsynaptic Potentials ,Glutamic Acid ,In Vitro Techniques ,Receptors, N-Methyl-D-Aspartate ,Synaptic Transmission ,Electric Stimulation ,Rats ,Kinetics ,Animals, Newborn ,Animals ,Receptors, AMPA ,Synaptic Vesicles ,Rats, Wistar ,alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid ,Brain Stem - Abstract
We have characterized developmental changes in the kinetics and quantal parameters of action potential (AP)-evoked neurotransmitter release during maturation of the calyx of Held synapse. Quantal size (q) and peak amplitudes of evoked EPSCs increased moderately, whereas the fraction of vesicles released by single APs decreased. During synaptic depression induced in postnatal day (P) 5-7 synapses by 10-100 Hz stimulation, q declined rapidly to 40-12% of its initial value. The decrease in q was generally smaller in more mature synapses (P12-14), but quite severe for frequenciesor = 300 Hz. The stronger decline of q in immature synapses resulted from a slower recovery from desensitization, presumably due to delayed glutamate clearance. Recovery from this desensitization followed an exponential time course with a time constant of approximately 480 ms in P5-7 synapses, and sped up20-fold during maturation. Deconvolution analysis of EPSCs revealed a significant acceleration of the release time course during development, which was accompanied by a 2-fold increase of the peak release rate. During long 100 Hz trains, more mature synapses were able to sustain average rates of 8-10 quanta s(-1) per active zone for phasic release. The rates of asynchronous vesicle release increased transiently35-fold immediately after such stimuli and decayed rapidly with an exponential time constant of approximately 50 ms to low resting levels of spontaneous release. However, even following extended periods of 100 Hz stimulation, the amount of asynchronous release was relatively minor with peak rates of less than 5% of the average rate of synchronous release measured at steady state during the tetani. Therefore, a multitude of mechanisms seems to converge on the generation of fast, temporally precise and reliable high-frequency transmission at the mature calyx of Held synapse.
- Published
- 2005
24. Allosteric modulation of the presynaptic Ca2+ sensor for vesicle fusion
- Author
-
Volker Scheuss, Ralf Schneggenburger, and Xuelin Lou
- Subjects
Vesicle fusion ,Chromaffin Cells ,Allosteric regulation ,Presynaptic Terminals ,In Vitro Techniques ,Synaptic vesicle ,Membrane Fusion ,Models, Biological ,Synaptic Transmission ,Allosteric Regulation ,Animals ,Calcium Signaling ,Protein kinase C ,Phorbol 12,13-Dibutyrate ,Physics ,Neurotransmitter Agents ,Multidisciplinary ,SNAP25 ,Excitatory Postsynaptic Potentials ,Long-term potentiation ,Kiss-and-run fusion ,Cell biology ,Rats ,Synapses ,Calcium ,Calyx of Held ,Brain Stem - Abstract
Neurotransmitter release is triggered by an increase in the cytosolic Ca2+ concentration ([Ca2+]i), but it is unknown whether the Ca2+-sensitivity of vesicle fusion is modulated during synaptic plasticity. We investigated whether the potentiation of neurotransmitter release by phorbol esters, which target presynaptic protein kinase C (PKC)/munc-13 signalling cascades, exerts a direct effect on the Ca2+-sensitivity of vesicle fusion. Using direct presynaptic Ca2+-manipulation and Ca2+ uncaging at a giant presynaptic terminal, the calyx of Held, we show that phorbol esters potentiate transmitter release by increasing the apparent Ca2+-sensitivity of vesicle fusion. Phorbol esters potentiate Ca2+-evoked release as well as the spontaneous release rate. We explain both effects by an increased fusion 'willingness' in a new allosteric model of Ca2+-activation of vesicle fusion. In agreement with an allosteric mechanism, we observe that the classically high Ca2+ cooperativity in triggering vesicle fusion (approximately 4) is gradually reduced below 3 microM [Ca2+]i, reaching a value of
- Published
- 2005
25. Rapid Functional Maturation of Nascent Dendritic Spines
- Author
-
Graham Knott, Karen Zito, Volker Scheuss, Travis C. Hill, and Karel Svoboda
- Subjects
musculoskeletal diseases ,Dendritic spine ,Patch-Clamp Techniques ,Time Factors ,Neuroscience(all) ,Dendritic Spines ,Long-Term Potentiation ,Synaptic Membranes ,Glutamic Acid ,AMPA receptor ,Hippocampal-Neurons ,Biology ,Hippocampal formation ,Hippocampus ,Synaptic Transmission ,Article ,MOLNEURO ,Postnatal-Development ,Actin remodeling of neurons ,Organ Culture Techniques ,Microscopy, Electron, Transmission ,Animals ,Immunogold Localization ,Calcium Signaling ,Receptors, AMPA ,Cortex In-Vivo ,Microscopy, Confocal ,Neuronal Plasticity ,General Neuroscience ,Pyramidal Cells ,Long-term potentiation ,Cell Differentiation ,musculoskeletal system ,Individual Excitatory Synapses ,Cell biology ,Dendritic filopodia ,Rats ,Spine (zoology) ,Nmda Receptors ,Postsynaptically Silent Synapses ,Synaptic plasticity ,Synapses ,Calcium ,Neuroscience ,Synaptic Plasticity ,Dependent Plasticity - Abstract
Spine growth and retraction with synapse formation and elimination plays an important role in shaping brain circuits during development and in the adult brain. Yet the temporal relationship between spine morphogenesis and the formation of functional synapses remains poorly defined. We imaged hippocampal pyramidal neurons to identify spines of different ages. We then used two-photon glutamate uncaging, whole-cell recording, and Ca2+ imaging to analyze the properties of nascent spines and their older neighbors. We found that new spines expressed glutamate sensitive currents that were indistinguishable from mature spines of comparable volumes. Some spines exhibited negligible AMPA receptor-mediated responses, but the occurrence of these ‘silent’ spines was uncorrelated with spine age. In contrast, NMDA receptor-mediated Ca2+ accumulations were significantly lower in new spines. New spines reconstructed using electron microscopy made synapses. Our data support a model in which outgrowth and enlargement of nascent spines is tightly coupled to formation and maturation of glutamatergic synapses.
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.