Von Der Malsburg Research Articles

IRQC, a surveillance pathway for 40S ribosomal quality control during mRNA translation initiation.

Post-translational modification of ribosomal proteins enables rapid and dynamic regulation of protein biogenesis. Site-specific ubiquitylation of 40S ribosomal proteins uS10 and eS10 plays a key role during ribosome-associated quality control (RQC). Distinct, and previously functionally ambiguous, ubiquitylation events on the 40S proteins uS3 and uS5 are induced by diverse proteostasis stressors that impact translation activity. Here, we identify the ubiquitin ligase RNF10 and the deubiquitylating enzyme USP10 as the key enzymes that regulate uS3 and uS5 ubiquitylation. Prolonged uS3 and uS5 ubiquitylation results in 40S, but not 60S, ribosomal protein degradation in a manner independent of canonical autophagy. We show that blocking progression of either scanning or elongating ribosomes past the start codon triggers site-specific ubiquitylation events on ribosomal proteins uS5 and uS3. This study identifies and characterizes a distinct arm in the RQC pathway, initiation RQC (iRQC), that acts on 40S ribosomes during translation initiation to modulate translation activity and capacity.

Failures of Gricean reasoning and the role of stereotypes in the production of gender marking in French

We partly replicate von der Malsburg et al. (2020)’s recent experiments investigating the relationship between speaker expectations, gender stereotypes and language use in English on a grammatical gender language: French. The results of our experiment show how the linguistic particularities of the English and French gender marking systems interact with speaker expectations and stereotypes to create different patterns of gender marking production. They also raise a puzzle for current theoretical and computational frameworks that formalize Gricean pragmatics, particularly those in which informativity (Gricean Quantity) is assumed to play a driving role in linguisticproduction.

How task demands influence scanpath similarity in a sequential number-search task

More and more researchers are considering the omnibus eye movement sequence—the scanpath—in their studies of visual and cognitive processing (e.g. Hayes, Petrov, & Sederberg, 2011; Madsen, Larson, Loschky, & Rebello, 2012; Ni et al., 2011; von der Malsburg & Vasishth, 2011). However, it remains unclear how recent methods for comparing scanpaths perform in experiments producing variable scanpaths, and whether these methods supplement more traditional analyses of individual oculomotor statistics. We address this problem for MultiMatch (Jarodzka et al., 2010; Dewhurst et al., 2012), evaluating its performance with a visual search-like task in which participants must fixate a series of target numbers in a prescribed order. This task should produce predictable sequences of fixations and thus provide a testing ground for scanpath measures. Task difficulty was manipulated by making the targets more or less visible through changes in font and the presence of distractors or visual noise. These changes in task demands led to slower search and more fixations. Importantly, they also resulted in a reduction in the between-subjects scanpath similarity, demonstrating that participants’ gaze patterns became more heterogenous in terms of saccade length and angle, and fixation position. This implies a divergent strategy or random component to eye-movement behaviour which increases as the task becomes more difficult. Interestingly, the duration of fixations along aligned vectors showed the opposite pattern, becoming more similar between observers in 2 of the 3 difficulty manipulations. This provides important information for vision scientists who may wish to use scanpath metrics to quantify variations in gaze across a spectrum of perceptual and cognitive tasks.

An applet for the Gabor similarity scaling of the differences between complex stimuli.

It is widely accepted that after the first cortical visual area, V1, a series of stages achieves a representation of complex shapes, such as faces and objects, so that they can be understood and recognized. A major challenge for the study of complex shape perception has been the lack of a principled basis for scaling of the physical differences between stimuli so that their similarity can be specified, unconfounded by early-stage differences. Without the specification of such similarities, it is difficult to make sound inferences about the contributions of later stages to neural activity or psychophysical performance. A Web-based app is described that is based on the Malsburg Gabor-jet model (Lades et al., 1993), which allows easy specification of the V1 similarity of pairs of stimuli, no matter how intricate. The model predicts the psycho physical discriminability of metrically varying faces and complex blobs almost perfectly (Yue, Biederman, Mangini, von der Malsburg, & Amir, 2012), and serves as the input stage of a large family of contemporary neurocomputational models of vision.

Self-organization of control circuits for invariant fiber projections.

Assuming that patterns in memory are represented as two-dimensional arrays of local features, just as they are in primary visual cortices, pattern recognition can take the form of elastic graph matching (Lades etal., 1993 ). Neural implementation of this may be based on preorganized fiber projections that can be activated rapidly with the help of control units (Wolfrum, Wolff, Lücke, & von der Malsburg, 2008 ). Each control unit governs a set of projection fibers that form part of a coherent mapping. We describe a mathematical model for the ontogenesis of the underlying connectivity based on a principle of network self-organization as described by the Häussler system (Häussler & von der Malsburg, 1983 ), modified to be sensitive to pattern similarity and to support formation of multiple mappings, each under the command of a control unit. The process takes the form of a soft-winner-take-all, where units compete for the representation of maps. We show simulations for invariant point-to-point and feature-to-feature mappings.

A Required Paradigm Shift in Today’s Vision Research

Christoph von der Malsburg obtained his Ph.D. in Heidelberg on a subject of particle physics. He worked at the Max-Planck-Institut fur biophysikalische Chemie in Gottingen from 1970 until 1987. Since 1988 he was professor of Computer Science at the University of Southern California (USC) and from 1990 he also codirected the Institute fur Neuroinformatik at the Ruhr-Universitat Bochum. Since 2006 he is Senior Fellow at the Frankfurt Institute for Advanced Studies (FIAS). In his work, he has made important contributions in the areas of pattern recognition and computational neuroscience. KI: You led the Institut fuer Neuroinformatik from 1990 until 2006 at the Ruhr-Universitat Bochum. I remember from the time I was a PhD student in your group that you were traveling between Los Angeles and Bochum back and forth twice a year. Now you are working at the Frankfurt Institute for Advanced Studies. Do you miss Bochum and Los Angeles in any way? Of course I miss them. At that time I had a large group of co-workers in both places. I had a lot of resources that I could use to develop systems. I now essentially work without any resources apart from a computer and an office. But I must say, I am enjoying both types of activity very much. KI: What are you concerned with in your current work? I think I have to collect my thoughts. I staged my life as an attempt to understand the brain and now is cash time. I have to write down my thoughts in a coherent fashion and see how far I have gotten in understanding the brain. KI: Your group was focusing in the first place on the vision problem with the aim to take the human brain as a model. What kind of knowledge about or which aspects of the brain were useful to derive vision algorithms? I think it is very important to know what the natural visual system can do and what it cannot do and, by this, to avoid putting up problems that cannot be solved at all. This is certainly one important kind of influence. The second one is that the brain is different from all of computer work in that it does not have a separate programmer. It starts with an initial condition, which has been developed by evolution, and from then on it is on its own resources. There are two ways it has to solve problems. One is by learning from examples and the other one is by some kind of self-organization or self-interaction in order to create structures that are more self-consistent. And then, of course, studying the brain has to come up with the perspective of a very simple basic data structure, which in the brain is in the form of neurons and their connections and their activity, which can express whatever is to be expressed. This is a drive towards homogeneity and simplicity. I think that is the most important lesson we can learn from the brain. KI: How would you judge the success of your group in retrospective? Well, it is the path and not the goal that is important. I think the group has achieved a lot—number one, of course, in founding careers. There are a number of professorships that arose from my institute and also a large number of students who have found good positions in industry. N. Kruger (&) The Maersk Mc-Kinney Moller Institute, Campusvej 55, 5230 Odense M, Denmark e-mail: norbert@mmmi.sdu.dk

Determinants of Scanpath Regularity in Reading.

Scanpaths have played an important role in classic research on reading behavior. Nevertheless, they have largely been neglected in later research perhaps due to a lack of suitable analytical tools. Recently, von der Malsburg and Vasishth (2011) proposed a new measure for quantifying differences between scanpaths and demonstrated that this measure can recover effects that were missed with the traditional eyetracking measures. However, the sentences used in that study were difficult to process and scanpath effects accordingly strong. The purpose of the present study was to test the validity, sensitivity, and scope of applicability of the scanpath measure, using simple sentences that are typically read from left to right. We derived predictions for the regularity of scanpaths from the literature on oculomotor control, sentence processing, and cognitive aging and tested these predictions using the scanpath measure and a large database of eye movements. All predictions were confirmed: Sentences with short words and syntactically more difficult sentences elicited more irregular scanpaths. Also, older readers produced more irregular scanpaths than younger readers. In addition, we found an effect that was not reported earlier: Syntax had a smaller influence on the eye movements of older readers than on those of young readers. We discuss this interaction of syntactic parsing cost with age in terms of shifts in processing strategies and a decline of executive control as readers age. Overall, our results demonstrate the validity and sensitivity of the scanpath measure and thus establish it as a productive and versatile tool for reading research.

Where does cognition occur: in one's head or in one's embodied/extended environment?

Turning points in science occur when an issue has reached maturity, when a critical mass of new facts cries out for a new synthesis, and when there is a general sense of urgency to reconsider basic assumptions" (von der Malsburg et al. 2010:xiii).

Encoding of Mixtures in a Simple Olfactory System

Natural odors are usually mixtures; yet, humans and animals can experience them as unitary percepts. Olfaction also enables stimulus categorization and generalization. We studied how these computations are performed with the responses of 168 locust antennal lobe projection neurons (PNs) to varying mixtures of two monomolecular odors, and of 174 PNs and 209 mushroom body Kenyon cells (KCs) to mixtures of up to eight monomolecular odors. Single-PN responses showed strong hypoadditivity and population trajectories clustered by odor concentration and mixture similarity. KC responses were much sparser on average than those of PNs and often signaled the presence of single components in mixtures. Linear classifiers could read out the responses of both populations in single time bins to perform odor identification, categorization, and generalization. Our results suggest that odor representations in the mushroom body may result from competing optimization constraints to facilitate memorization (sparseness) while enabling identification, classification, and generalization.

SGTA Recognizes a Noncanonical Ubiquitin-like Domain in the Bag6-Ubl4A-Trc35 Complex to Promote Endoplasmic Reticulum-Associated Degradation

Elimination of aberrantly folded polypeptides from the endoplasmic reticulum (ER) by the ER-associated degradation (ERAD) system promotes cell survival under stress conditions. This quality control mechanism requires movement of misfolded proteins across the ER membrane for targeting to the cytosolic proteasome, a process facilitated by a "holdase" complex, consisting of Bag6 and the cofactors Ubl4A and Trc35. This multiprotein complex also participates in several other protein quality control processes. Here, we report SGTA as a component of the Bag6 system, which cooperates with Bag6 to channel dislocated ERAD substrates that are prone to aggregation. Using nuclear magnetic resonance spectroscopy and biochemical assays, we demonstrate that SGTA contains a noncanonical ubiquitin-like-binding domain that interacts specifically with an unconventional ubiquitin-like protein/domain in Ubl4A at least in part via electrostatics. This interaction helps recruit SGTA to Bag6, enhances substrate loading to Bag6, and thus prevents the formation of nondegradable protein aggregates in ERAD.

Expression of Saccharomyces cerevisiae Sdh3p and Sdh4p Paralogs Results in Catalytically Active Succinate Dehydrogenase Isoenzymes

Succinate dehydrogenase (SDH), also known as complex II, is required for respiratory growth; it couples the oxidation of succinate to the reduction of ubiquinone. The enzyme is composed of two domains. A membrane-extrinsic catalytic domain composed of the Sdh1p and Sdh2p subunits harbors the flavin and iron-sulfur cluster cofactors. A membrane-intrinsic domain composed of the Sdh3p and Sdh4p subunits interacts with ubiquinone and may coordinate a b-type heme. In many organisms, including Saccharomyces cerevisiae, possible alternative SDH subunits have been identified in the genome. S. cerevisiae contains one paralog of the Sdh3p subunit, Shh3p (YMR118c), and two paralogs of the Sdh4p subunit, Shh4p (YLR164w) and Tim18p (YOR297c). We cloned and expressed these alternative subunits. Shh3p and Shh4p were able to complement Δsdh3 and Δsdh4 deletion mutants, respectively, and support respiratory growth. Tim18p was unable to do so. Microarray and proteomics data indicate that the paralogs are expressed under respiratory and other more restrictive growth conditions. Strains expressing hybrid SDH enzymes have distinct metabolic profiles that we distinguished by (1)H NMR analysis of metabolites. Surprisingly, the Sdh3p subunit can form SDH isoenzymes with Sdh4p or with Shh4p as well as be a subunit of the TIM22 mitochondrial protein import complex.

Heterosynaptic plasticity induced by intracellular tetanization in layer 2/3 pyramidal neurons in rat auditory cortex

Associative Hebbian-type synaptic plasticity underlies the mechanisms of learning and memory; however, Hebbian learning rules lead to runaway dynamics of synaptic weights and lack mechanisms for synaptic competition.Heterosynaptic plasticity may solve these problems by complementing plasticity at synapses that were active during the induction, with opposite-sign changes at non-activated synapses. In visual cortex, a potential candidate mechanism for normalization is plasticity induced by a purely postsynaptic protocol, intracellular tetanization. Here we asked if intracellular tetanization can induce long-term plasticity in auditory cortex. We recorded excitatory postsynaptic potentials (EPSPs) of regular (n =76) and all-or-none (n =24) type in layer 2/3 pyramidal cells in slices from rat auditory cortex. After intracellular tetanization, 32 of 76 regular inputs (42%) showed long-term depression, 21 inputs (28%) showed potentiation and 23 inputs (30%) did not change. The direction of plasticity correlated with the initial release probability: inputs with initially low release probability tended to be potentiated, while inputs with high release probability tended to be depressed. Thus, intracellular tetanization had a normalizing effect on synaptic efficacy. Induction of plasticity by intracellular tetanization required a rise of intracellular [Ca(2+)], because it was impaired by chelating intracellular calcium with EGTA. The long-term changes induced by intracellular tetanization involved both pre and postsynaptic mechanisms. EPSP amplitude changes were correlated with changes of release indices: paired-pulse ratio and the inverse of the coefficient of variation (CV(-2)). Furthermore at some all-or-none synapses, changes of averaged response amplitude were correlated with a change of the failure rate, without a change of the synaptic potency, measured as averaged amplitude of successful responses. Presynaptic components of plastic changes were abolished in experiments with blockade of NO-synthesis and spread, indicating involvement of NO signalling. These results demonstrate that the ability of purely postsynaptic challenges to induce plasticity is a general property of pyramidal neurons of both auditory and visual cortices.

MINOS Is Plus: A Mitofilin Complex for Mitochondrial Membrane Contacts

Cristae junctions mark the boundaries of respiratory compartments in the inner mitochondrial membrane. In this issue of Developmental Cell, von der Malsburg etal. (2011) identify a complex, MINOS, that organizes cristae junctions. Mitofilin/Fcj1, the central component of the MINOS complex, also connects the inner membrane to outer membrane protein import machinery.

One cell to rule them all, and in the dendrites bind them

One cell to rule them all, and in the dendrites bind them

Characterization of single unit synchronization patterns in the primate fronto-parietal reach network

Characterization of single unit synchronization patterns in the primate fronto-parietal reach network

STDP: spiking, timing, rates and beyond

STDP: spiking, timing, rates and beyond

Complex Systems Science and Brain Dynamics: A Frontiers in Computational Neuroscience Special Topic

Complex Systems Science and Brain Dynamics: A Frontiers in Computational Neuroscience Special Topic

Synergetic analysis of the Häussler-von der Malsburg equations for manifolds of arbitrary geometry

We generalize a model of Haussler and von der Malsburg which describes the self-organized generation of retinotopic projections between two one-dimensional discrete cell arrays on the basis of cooperative and competitive interactions of the individual synaptic contacts. Our generalized model is independent of the special geometry of the cell arrays and describes the temporal evolution of the connection weights between cells on different manifolds. By linearizing the equations of evolution around the stationary uniform state we determine the critical global growth rate for synapses onto the tectum where an instability arises. Within a nonlinear analysis we use then the methods of synergetics to adiabatically eliminate the stable modes near the instability. The resulting order parameter equations describe the emergence of retinotopic projections from initially undifferentiated mappings independent of dimension and geometry.

Synergetic analysis of the Häussler‐von der Malsburg equations for manifolds of arbitrary geometry

AbstractWe generalize a model of Häussler and von der Malsburg which describes the self‐organized generation of retinotopic projections between two one‐dimensional discrete cell arrays on the basis of cooperative and competitive interactions of the individual synaptic contacts. Our generalized model is independent of the special geometry of the cell arrays and describes the temporal evolution of the connection weights between cells on different manifolds. By linearizing the equations of evolution around the stationary uniform state we determine the critical global growth rate for synapses onto the tectum where an instability arises. Within a nonlinear analysis we use then the methods of synergetics to adiabatically eliminate the stable modes near the instability. The resulting order parameter equations describe the emergence of retinotopic projections from initially undifferentiated mappings independent of dimension and geometry.

Solutions of the Häussler‐von der Malsburg equations in manifolds with constant curvatures*

AbstractWe apply generic order parameter equations for the emergence of retinotopy between manifolds of different geometry to one‐ and two‐dimensional Euclidean and spherical manifolds. To this end we elaborate both a linear and a nonlinear synergetic analysis which results in order parameter equations for the dynamics of connection weights between two cell sheets. Our results for strings are analogous to those for discrete linear chains obtained previously by Häussler and von der Malsburg. The case of planes turns out to be more involved as the two dimensions do not decouple in a trivial way. However, superimposing two modes under suitable conditions provides a state with a pronounced retinotopic character. In the case of spherical manifolds we show that the order parameter equations provide stable stationary solutions which correspond to retinotopic modes. A further analysis of higher modes furnishes proof that our model describes the emergence of a perfect one‐to‐one retinotopy between two spheres.