Bernstein Center for Computational Neuroscience Munich

Bernstein, Germany

Bernstein Center for Computational Neuroscience Munich

Bernstein, Germany
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Papper M.,Ludwig Maximilians University of Munich | Kempter R.,Humboldt University of Berlin | Kempter R.,Bernstein Center for Computational Neuroscience Berlin | Leibold C.,Ludwig Maximilians University of Munich | Leibold C.,Bernstein Center for Computational Neuroscience Munich
Learning and Memory | Year: 2011

Long-term synaptic plasticity exhibits distinct phases. The synaptic tagging hypothesis suggests an early phase in which synapses are prepared, or "tagged," for protein capture, and a late phase in which those proteins are integrated into the synapses to achieve memory consolidation. The synapse specificity of the tags is consistent with conventional neural network models of associative memory. Memory consolidation through protein synthesis, however, is neuron specific, and its functional role in those models has not been assessed. Here, using a theoretical network model, we test the tagging hypothesis on its potential to prolong memory lifetimes in an online-learning paradigm. We find that protein synthesis, though not synapse specific, prolongs memory lifetimes if it is used to evaluate memory items on a cellular level. In our model we assume that only "important" memory items evoke protein synthesis such that these become more stable than "unimportant" items, which do not evoke protein synthesis. The network model comprises an equilibrium distribution of synaptic states that is very susceptible to the storage of new items: Most synapses are in a state in which they are plastic and can be changed easily, whereas only those synapses that are essential for the retrieval of the important memory items are in the stable late phase. The model can solve the distal reward problem, where the initial exposure of a memory item and its evaluation are temporally separated. Synaptic tagging hence provides a viable mechanism to consolidate and evaluate memories on a synaptic basis. © 2011 Cold Spring Harbor Laboratory Press.

Bolinger D.,Max Planck Institute of Neurobiology | Bolinger D.,Bernstein Center for Computational Neuroscience Munich | Gollisch T.,Max Planck Institute of Neurobiology | Gollisch T.,Bernstein Center for Computational Neuroscience Munich | And 2 more authors.
Neuron | Year: 2012

Neurons often integrate information from multiple parallel signaling streams. How a neuron combines these inputs largely determines its computational role in signal processing. Experimental assessment of neuronal signal integration, however, is often confounded by cell-intrinsic nonlinear processes that arise after signal integration has taken place. To overcome this problem and determine how ganglion cells in the salamander retina integrate visual contrast over space, we used automated online analysis of recorded spike trains and closed-loop control ofthe visual stimuli to identify different stimulus patterns that give the same neuronal response. These iso-response stimuli revealed a threshold-quadratic transformation as a fundamental nonlinearity within the receptive field center. Moreover, fora subset of ganglion cells, the method revealed an additional dynamic nonlinearity that renders thesecells particularly sensitive to spatially homogeneous stimuli. This function is shown to arise from a local inhibition-mediated dynamic gain control mechanism. Understanding mechanisms of neuronal signal integration is complicated by cell-intrinsic nonlinear processes arising after integration has taken place. Bölinger and Gollisch assess how nonlinearities affect signal integration in retinal ganglion cells (RGCs), revealing mechanisms that provide some RGCs with particular sensitivity to spatially homogeneous stimulation. © 2012 Elsevier Inc.

Beed P.,Charité - Medical University of Berlin | Bendels M.H.K.,Charité - Medical University of Berlin | Wiegand H.F.,Charité - Medical University of Berlin | Leibold C.,Bernstein Center for Computational Neuroscience Munich | And 4 more authors.
Neuron | Year: 2010

Medial entorhinal cortex (MEC) plays an important role in physiological processes underlying navigation, learning, and memory. Excitatory cells in the different MEC layers project in a region-specific manner to the hippocampus. However, the intrinsic microcircuitry of the main excitatory cells in the superficial MEC layers is largely unknown. Using scanning photostimulation, we investigated the functional microcircuitry of two such cell types, stellate and pyramidal cells. We found cell-type-specific intralaminar and ascending interlaminar feedback inputs. The ascending interlaminar inputs display distinct organizational principles depending on the cell-type and its position within the superficial lamina: the spatial spread of inputs for stellate cells is narrower than for pyramidal cells, while inputs to pyramidal cells in layer 3, but not in layer 2, exhibit an asymmetric offset to the medial side of the cell's main axis. Differential laminar sources of excitatory inputs might contribute to the functional diversity of stellate and pyramidal cells. © 2010 Elsevier Inc.

Porres C.P.,Ludwig Maximilians University of Munich | Meyer E.M.M.,Ludwig Maximilians University of Munich | Meyer E.M.M.,Friedrich Miescher Institute for Biomedical Research | Grothe B.,Ludwig Maximilians University of Munich | And 2 more authors.
Journal of Neuroscience | Year: 2011

Neurons in the dorsal nucleus of the lateral lemniscus (DNLL) receive excitatory and inhibitory inputs from the superior olivary complex (SOC) and convey GABAergic inhibition to the contralateral DNLL and the inferior colliculi. Unlike the fast glycinergic inhibition in the SOC, this GABAergic inhibition outlasts auditory stimulation by tens of milliseconds. Two mechanisms have been postulated to explain this persistent inhibition. One, an "integration-based" mechanism, suggests that postsynaptic excitatory integration in DNLL neurons generates prolonged activity, and the other favors the synaptic time course of the DNLL output itself. The feasibility of the integration-based mechanism was tested in vitro in DNLL neurons of Mongolian gerbils by quantifying the cellular excitability and synaptic input-output functions (IO-Fs). All neurons were sustained firing and generated a near monotonic IO-F on current injections. From synaptic stimulations, we estimate that activation of approximately five fibers, each on average liberating ∼18 vesicles, is sufficient to trigger a single postsynaptic action potential. A strong single pulse of afferent fiber stimulation triggered multiple postsynaptic action potentials. The steepness of the synaptic IO-F was dependent on the synaptic NMDA component. The synaptic NMDA receptor current defines the slope of the synaptic IO-F by enhancing the temporal and spatial EPSP summation. Blocking this NMDA-dependent amplification during postsynaptic integration of train stimulations resulted into a ∼20%reduction of the decay time course of the GABAergic inhibition. Thus, our data show that the NMDA-dependent amplification of the postsynaptic activity contributes to the GABAergic persistent inhibition generated by DNLL neurons. Copyright © 2011 the authors.

Kammerer A.,Ludwig Maximilians University of Munich | Tejero-Cantero A.,Ludwig Maximilians University of Munich | Tejero-Cantero A.,Bernstein Center for Computational Neuroscience Munich | Leibold C.,Ludwig Maximilians University of Munich | Leibold C.,Bernstein Center for Computational Neuroscience Munich
Journal of Computational Neuroscience | Year: 2013

Recurring sequences of neuronal activation in the hippocampus are a candidate for a neurophysiological correlate of episodic memory. Here, we discuss a mean-field theory for such spike sequences in phase space and show how they become unstable when the neuronal network operates at maximum memory capacity. We find that inhibitory feedback rescues replay of the sequences, giving rise to oscillations and thereby enhancing the network's capacity. We further argue that transient sequences in an overloaded network with feedback inhibition may provide a mechanistic picture of memory-related neuronal activity during hippocampal sharp-wave ripple complexes. © Springer Science+Business Media, LLC 2012.

Siveke I.,Ludwig Maximilians University of Munich | Leibold C.,Ludwig Maximilians University of Munich | Leibold C.,Bernstein Center for Computational Neuroscience Munich | Schiller E.,Ludwig Maximilians University of Munich | And 2 more authors.
Journal of Neuroscience | Year: 2012

Interaural differences in stimulus intensity and timing are major cues for sound localization. In mammals, these cues are first processed in the lateral and medial superior olive by interaction of excitatory and inhibitory synaptic inputs from ipsi-and contralateral cochlear nucleus neurons. To preserve sound localization acuity following changes in the acoustic environment, the processing of these binaural cues needs neuronal adaptation. Recent studies have shown that binaural sensitivity adapts to stimulation history within milliseconds, but the actual extent of binaural adaptation is unknown. In the current study, we investigated long-term effects on binaural sensitivity using extracellular in vivo recordings from single neurons in the dorsal nucleus of the lateral lemniscus that inherit their binaural properties directly from the lateral and medial superior olives. In contrast to most previous studies, we used a noninvasive approach to influence this processing. Adult gerbils were exposed for 2 weeks to moderate noise with no stable binaural cue. We found monaural response properties to be unaffected by this measure. However, neuronal sensitivity to binaural cues was reversibly altered for a few days. Computational models of sensitivity to interaural time and level differences suggest that upregulation of inhibition in the superior olivary complex can explain the electrophysiological data. © 2012 the authors.

Couchman K.,Ludwig Maximilians University of Munich | Grothe B.,Ludwig Maximilians University of Munich | Grothe B.,Bernstein Center for Computational Neuroscience Munich | Felmy F.,Ludwig Maximilians University of Munich
Journal of Neuroscience | Year: 2010

Neurons in the medial superior olive (MSO) process microsecond interaural time differences, the major cue for localizing low-frequency sounds, by comparing the relative arrival time of binaural, glutamatergic excitatory inputs. This coincidence detection mechanism is additionally shaped by highly specialized glycinergic inhibition. Traditionally, it is assumed that the binaural inputs are conveyed by many independent fibers, but such an anatomical arrangement may decrease temporal precision. Short-term depression on the other hand might enhance temporal fidelity during ongoing activity. For the first time we show that binaural coincidence detection in MSO neurons may require surprisingly few but strong inputs, challenging long-held assumptions about mammalian coincidence detection. This study exclusively uses adult gerbils for in vitro electrophysiology, single-cell electroporation and immunohistochemistry to characterize the size and short-term plasticity of inputs to the MSO. We find that the excitatory and inhibitory inputs to the MSO are well balanced both in strength and short-term dynamics, redefining this fastest of all mammalian coincidence detector circuits. Copyright © 2010 the authors.

Schnaitmann C.,Max Planck Institute For Neurobiologie | Schnaitmann C.,Albert Ludwigs University of Freiburg | Garbers C.,Ludwig Maximilians University of Munich | Wachtler T.,Ludwig Maximilians University of Munich | And 3 more authors.
Current Biology | Year: 2013

Background Color vision is commonly assumed to rely on photoreceptors tuned to narrow spectral ranges. In the ommatidium of Drosophila, the four types of so-called inner photoreceptors express different narrow-band opsins. In contrast, the outer photoreceptors have a broadband spectral sensitivity and were thought to exclusively mediate achromatic vision. Results Using computational models and behavioral experiments, we demonstrate that the broadband outer photoreceptors contribute to color vision in Drosophila. The model of opponent processing that includes the opsin of the outer photoreceptors scored the best fit to wavelength discrimination data. To experimentally uncover the contribution of individual photoreceptor types, we restored phototransduction of targeted photoreceptor combinations in a blind mutant. Dichromatic flies with only broadband photoreceptors and one additional receptor type can discriminate different colors, indicating the existence of a specific output comparison of the outer and inner photoreceptors. Furthermore, blocking interneurons postsynaptic to the outer photoreceptors specifically impaired color but not intensity discrimination. Conclusions Our findings show that receptors with a complex and broad spectral sensitivity can contribute to color vision and reveal that chromatic and achromatic circuits in the fly share common photoreceptors. © 2013 Elsevier Ltd.

Walz H.,Bernstein Center for Computational Neuroscience Munich | Hupe G.J.,University of Ottawa | Benda J.,University of Tübingen | Lewis J.E.,University of Ottawa
Journal of Physiology Paris | Year: 2013

Weakly-electric fish are a well-established model system for neuroethological studies on communication and aggression. Sensory encoding of their electric communication signals, as well as behavioural responses to these signals, have been investigated in great detail under laboratory conditions. In the wave-type brown ghost knifefish, Apteronotus leptorhynchus, transient increases in the frequency of the generated electric field, called chirps, are particularly well-studied, since they can be readily evoked by stimulating a fish with artificial signals mimicking conspecifics. When two fish interact, both their quasi-sinusoidal electric fields (called electric organ discharge, EOD) superimpose, resulting in a beat, an amplitude modulation at the frequency difference between the two EODs. Although chirps themselves are highly stereotyped signals, the shape of the amplitude modulation resulting from a chirp superimposed on a beat background depends on a number of parameters, such as the beat frequency, modulation depth, and beat phase at which the chirp is emitted. Here we review the influence of these beat parameters on chirp encoding in the three primary stages of the electrosensory pathway: electroreceptor afferents, the hindbrain electrosensory lateral line lobe, and midbrain torus semicircularis. We then examine the role of these parameters, which represent specific features of various social contexts, on the behavioural responses of A. leptorhynchus. Some aspects of the behaviour may be explained by the coding properties of early sensory neurons to chirp stimuli. However, the complexity and diversity of behavioural responses to chirps in the context of different background parameters cannot be explained solely on the basis of the sensory responses and thus suggest that critical roles are played by higher processing stages. © 2012 Elsevier Ltd.

Walz H.,Bernstein Center for Computational Neuroscience Munich | Grewe J.,Bernstein Center for Computational Neuroscience Munich | Grewe J.,University of Tübingen | Benda J.,University of Tübingen
Journal of Neurophysiology | Year: 2014

Although communication signals often vary continuously on the underlying signal parameter, they are perceived as distinct categories. We here report the opposite case where an electrocommunication signal is encoded in four distinct regimes, although the behavior described to date does not show distinct categories. In particular, we studied the encoding of chirps by P-unit afferents in the weakly electric fish Apteronotus leptorhynchus. These fish generate an electric organ discharge that oscillates at a certain individual-specific frequency. The interaction of two fish in communication contexts leads to the emergence of a beating amplitude modulation (AM) at the frequency difference between the two individual signals. This frequency difference represents the social context of the encounter. Chirps are transient increases of the fish's frequency leading to transient changes in the frequency of the AM. We stimulated the cells with the same chirp on different, naturally occurring backgrounds beats. The P-units responded either by synchronization or desynchronization depending on the background. Although the duration of a chirp is often shorter than a full cycle of the AM it elicits, the distinct responses of the P-units to the chirp can be predicted solely from the frequency of the AM based on the static frequency tuning of the cells. © 2014 the American Physiological Society.

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