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Peter König

Publications and source records attributed to Peter König.

At least 19 recordsLinked to original sources
PubMed2006

A model of the ventral visual system based on temporal stability and local memory.

The cerebral cortex is a remarkably homogeneous structure suggesting a rather generic computational machinery. Indeed, under a variety of conditions, functions attributed to specialized areas can be supported by other regions. However, a host of studies have laid out an ever more detailed map of functional cortical areas. This leaves us with the puzzle of whether different cortical areas are intrinsically specialized, or whether they differ mostly by their position in the processing hierarchy and their inputs but apply the same computational principles. Here we show that the computational principle of optimal stability of sensory representations combined with local memory gives rise to a hierarchy of processing stages resembling the ventral visual pathway when it is exposed to continuous natural stimuli. Early processing stages show receptive fields similar to those observed in the primary visual cortex. Subsequent stages are selective for increasingly complex configurations of local features, as observed in higher visual areas. The last stage of the model displays place fields as observed in entorhinal cortex and hippocampus. The results suggest that functionally heterogeneous cortical areas can be generated by only a few computational principles and highlight the importance of the variability of the input signals in forming functional specialization.

Cerebral Cortex↗
PubMed2006

Development of effective quantum mechanical/molecular mechanical (QM/MM) methods for complex biological processes.

Motivated by the long-term goal of understanding vectorial biological processes such as proton transport (PT) in biomolecular ion pumps, a number of developments were made to establish combined quantum mechanical/molecular mechanical (QM/MM) methods suitable for studying chemical reactions involving significant charge separation in the condensed phase. These developments were summarized and discussed with representative problems. Specifically, free energy perturbation and boundary potential methods for treating long-range electrostatics were implemented to test the robustness of QM/MM results for protein systems. It was shown that consistent models with sufficient sampling were able to produce quantitatively satisfactory results, such as pKa for titritable groups in the interior of T4-lysozyme, while an inconsistent treatment of electrostatics or lack of sufficient sampling may produce incorrect results. Modifications were made to an approximate density functional theory (SCC-DFTB) to improve the description of proton affinity and hydrogen-bonding, which are crucial for the treatment of PT in polar systems. Test calculations on water autoionization showed clearly that both improvements are necessary for quantitatively reliable results. Finally, the newly established SCC-DFTB/MM-GSBP protocol was used to explore mechanistic issues in carbonic anhydrase (CA). Preliminary results suggest that PT in CA occurs mainly through short water wires containing two water molecules in a thermally activated fashion. Although longer water wires occur with similar frequencies, PT along those pathways, on average, has substantially higher barriers, a result not expected based on previous studies. The fluctuations of water molecules peripheral to the water wire were found to make a larger impact on the PT energetics compared to polar protein residues in the active site, which are largely pre-organized and therefore have less tendency to reorganize during the reaction.

Computer Simulation↗
PubMed2006

Hypoxia induces production of nitric oxide and reactive oxygen species in glomus cells of rat carotid body.

The carotid body is an arterial chemoreceptor organ that senses arterial pO(2) and pH. Previous studies have indicated that both reactive oxygen species (ROS) and nitric oxide (NO) are important potential mediators that may be involved in the response of the carotid body to hypoxia. However, whether their production by the chemosensitive elements of the carotid body is indeed oxygen-dependent is currently unclear. Thus, we have investigated their production under normoxic (20% O(2)) and hypoxic (1% O(2)) conditions in slice preparations of the rat carotid body by using fluorescent indicators and confocal microscopy. NO-synthesizing enzymes were identified by immunohistochemistry and histochemistry, and the subcellular localization of the NO-sensitive indicator diaminofluorescein was determined by a photoconversion technique and electron microscopy. Glomus cells of the carotid body responded to hypoxia by increases in both ROS and NO production. The hypoxia-induced increase in NO generation required (to a large extent, but not completely) extracellular calcium. Glomus cells were immunoreactive to endothelial NO synthase but not to the neuronal or inducible isoforms. Ultrastructurally, the NO-sensitive indicator was observed in mitochondrial membranes after exposure to hypoxia. The data show that glomus cells respond to exposure to hypoxia by the enhanced production of both ROS and NO. NO production by glomus cells is probably mediated by endothelial NO synthase, which is activated by calcium influx. The presence of NO indicator in mitochondria suggests the hypoxic regulation of mitochondrial function via NO in glomus cells.

Animals↗
PubMed2006

Symbols as self-emergent entities in an optimization process of feature extraction and predictions.

In the mammalian cortex the early sensory processing can be characterized as feature extraction resulting in local and analogue low-level representations. As a direct consequence, these map directly to the environment, but interpretation under natural conditions is ambiguous. In contrast, high-level representations for cognitive processing, e.g. language, require symbolic representations characterized by expression and syntax. The representations are binary, structured and disambiguated. However, do these fundamental functional distinctions translate into a fundamental distinction of the respective brain areas and their anatomical and physiological properties? Here we argue that the distinction between early sensory processing and higher cognitive functions may not be based on structural differences of cortical areas; instead similar learning principles acting on input signals with different statistics give rise to the observed variations of function. Firstly, we give an account of present research describing neuronal properties at early stages of sensory systems as a consequence of an optimization process over the set of natural stimuli. Secondly, addressing a stage following early visual processing we suggest to extend the unsupervised learning scheme by including predictive processes. These contain the widely used objective of temporal coherence as a special case and are a powerful approach to resolve ambiguities. Furthermore, in combination with a prior on the bandwidth of information exchange between units it leads to a condensation of information. Thirdly, as a crucial step, not only are predictive units optimized, but the selectivity of the feature extractors are adapted to allow optimal predictability. Thus, over and beyond making useful predictions, we propose that the predictability of a stimulus be in itself a selection criterion for further processing. In a hierarchical system the combined optimization process leads to entities that represent condensed pieces of knowledge and that are not analogue anymore. Instead, these entities work as arguments in a framework of transformations that realize predictions. Thus, the criteria of predictability and condensation in an optimization of sensory representations relate directly to the two defining properties of symbols of expression and syntax. In this paper, we sketch an unsupervised learning process that gradually transforms analogue local representations into discrete binary representations by means of four hypotheses. We propose that in this optimization process acting in a hierarchical system, entities emerge at, higher levels that fulfil the criteria defining symbols, instantiating qualitatively different representations at similarly structured low and high levels.

Animals↗
PubMed2005

Differences of monkey and human overt attention under natural conditions.

Rhesus monkeys are widely used as animal models of human attention. Such research rests upon the assumption that similar mechanisms underlie attention in both species. Here, we directly compare the influence of low-level stimulus features on overt attention in monkeys and humans under natural conditions. We recorded eye-movements in humans and rhesus monkeys during free-viewing of natural images. We find that intrinsic low-level features, such luminance-contrast, texture-contrast and saliency-as predicted by a standard model, are elevated at fixation points in the majority of images. These correlative effects are not significantly different between species. However, local image modifications affect both species differently: moderate modifications, which are in the range of natural fluctuations, attract overt attention in monkeys significantly stronger than they do in humans. In addition, humans show a higher inter-individual consistency regarding which locations they fixate than monkeys, in spite of the similarity for intrinsic low-level features. Taken together, these data demonstrate that-under natural conditions-low-level stimulus features affect attention in monkeys and humans differently.

Animals↗
PubMed2005

Down-regulation of vasoactive intestinal peptide and altered expression of its receptors in rat diabetic cardiomyopathy.

Vasoactive intestinal peptide (VIP) is a vasorelaxant peptide that addresses two receptor subtypes, VPAC1 and VPAC2. It stimulates insulin secretion and mediates anti-inflammatory effects and has been proposed for treatment of type 2 and autoimmune diabetes. In the heart, VIP is produced and released primarily by intrinsic neurons and improves cardiac perfusion and function. Here, we investigated the involvement of this system in the events underlying development of experimentally induced diabetic cardiomyopathy. Rats received a single streptozotocin injection, and cardiac VIP content [radioimmune assay (RIA)], expression of the VIP precursors VPAC1 and VPAC2 [real-time reverse transcription-polymerase chain reaction (RT-PCR)], and VPAC1 and VPAC2 tissue distribution (immunohistochemistry) were assessed 4, 8, and 16 weeks thereafter and compared with corresponding vehicle-treated controls. Cardiac neuropathy manifests progressively during the first 4 months of diabetes at the preproVIP mRNA and VIP peptide level and is accompanied by initial down-regulation of VPAC2 at one prime target of VIP-containing axons, i.e., smooth muscle cells of coronary arterioles. VPAC1 is expressed by macrophages. After initial changes that are specific for atria and ventricles, respectively, VPAC1 and VPAC2 expression return to control levels at 16 weeks despite ongoing loss of VIP. Given the cardioprotective role of the VIP signaling system, the persistence of receptors has therapeutic implications since it is the prerequisite for trials with VPAC2 agonists.

Animals↗
PubMed2005

Texture signals in whisker vibrations.

Rodents excel in making texture judgments by sweeping their whiskers across a surface. Here we aimed to identify the signals present in whisker vibrations that give rise to such fine sensory discriminations. First, we used sensors to capture vibration signals in metal whiskers during active whisking of an artificial system and in natural whiskers during whisking of rats in vivo. Then we developed a classification algorithm that successfully matched the vibration frequency spectra of single trials to the texture that induced it. For artificial whiskers, the algorithm correctly identified one texture of eight alternatives on 40% of trials; for in vivo natural whiskers, the algorithm correctly identified one texture of five alternatives on 80% of trials. Finally, we asked which were the key discriminative features of the vibration spectra. Under both artificial and natural conditions, the combination of two features accounted for most of the information: The modulation power-the power of the part of the whisker movement representing the modulation due to the texture surface-increased with the coarseness of the texture; the modulation centroid-a measure related to the center of gravity within the power spectrum-decreased with the coarseness of the texture. Indeed, restricting the signal to these two parameters led to performance three-fourths as high as the full spectra. Because earlier work showed that modulation power and centroid are directly related to neuronal responses in the whisker pathway, we conclude that the biological system optimally extracts vibration features to permit texture classification.

Action Potentials↗
PubMed2005

Beyond sensory substitution--learning the sixth sense.

Rapid advances in neuroscience have sparked numerous efforts to study the neural correlate of consciousness. Prominent subjects include higher sensory area, distributed assemblies bound by synchronization of neuronal activity and neurons in specific cortical laminae. In contrast, it has been suggested that the quality of sensory awareness is determined by systematic change of afferent signals resulting from behaviour and knowledge thereof. Support for such skill-based theories of perception is provided by experiments on sensory substitution. Here, we pursue this line of thought and create new sensorimotor contingencies and, hence, a new quality of perception. Adult subjects received orientation information, obtained by a magnetic compass, via vibrotactile stimulation around the waist. After six weeks of training we evaluated integration of the new input by a battery of tests. The results indicate that the sensory information provided by the belt (1) is processed and boosts performance, (2) if inconsistent with other sensory signals leads to variable performance, (3) does interact with the vestibular nystagmus and (4) in half of the experimental subjects leads to qualitative changes of sensory experience. These data support the hypothesis that new sensorimotor contingencies can be learned and integrated into behaviour and affect perceptual experience.

Adaptation, Physiological↗
PubMed2005

Learning viewpoint invariant object representations using a temporal coherence principle.

Invariant object recognition is arguably one of the major challenges for contemporary machine vision systems. In contrast, the mammalian visual system performs this task virtually effortlessly. How can we exploit our knowledge on the biological system to improve artificial systems? Our understanding of the mammalian early visual system has been augmented by the discovery that general coding principles could explain many aspects of neuronal response properties. How can such schemes be transferred to system level performance? In the present study we train cells on a particular variant of the general principle of temporal coherence, the "stability" objective. These cells are trained on unlabeled real-world images without a teaching signal. We show that after training, the cells form a representation that is largely independent of the viewpoint from which the stimulus is looked at. This finding includes generalization to previously unseen viewpoints. The achieved representation is better suited for view-point invariant object classification than the cells' input patterns. This property to facilitate view-point invariant classification is maintained even if training and classification take place in the presence of an--also unlabeled--distractor object. In summary, here we show that unsupervised learning using a general coding principle facilitates the classification of real-world objects, that are not segmented from the background and undergo complex, non-isomorphic, transformations.

Action Potentials↗
PubMed2005

Most peptide-containing sensory neurons lack proteins for exocytotic release and vesicular transport of glutamate.

We used multiple-labeling immunohistochemistry and confocal microscopy to examine co-expression of immunoreactivity for vesicular glutamate transporters (VGluTs), synaptic vesicle proteins, and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in peptide-containing sensory neurons of guinea pigs, mice, and toads. Axon terminals in the superficial layers of the dorsal horn of the spinal cord with immunoreactivity (IR) for both substance P (SP) and calcitonin gene-related peptide (CGRP) lacked IR for synaptosome-associated protein of 25 kDa (SNAP-25), syntaxin, synaptotagmin, synaptophysin, and synapsin, although adjacent varicosities without neuropeptides had IR for these synaptic proteins. Similarly, peptide-containing axon terminals in the superficial dorsal horn lacked IR for VGluT1 and VGluT2, despite the presence of VGluT2-IR in nearby nonpeptide varicosities. VGluT3-IR was sparse in the dorsal horn of the mouse spinal cord and was not present in peptide-containing axons. Most peripheral terminals of sensory neurons with both SP-IR and CGRP-IR in the skin, viscera, and autonomic ganglia of guinea pigs and mice also lacked IR for synaptic vesicle proteins, SNARE proteins, VGluT1, and VGluT2. In dorsal root ganglia from guinea pigs and mice, most small neurons with IR for both SP and CGRP lacked IR for SNAP-25, VGluT1, and VGluT2. Thus, proteins considered essential for vesicular uptake and exocytotic release of glutamate are not expressed at detectable levels by most sensory neurons containing SP and CGRP in rodents and toads. These data raise the possibility that most peptide-containing sensory neurons may not normally release glutamate as a transmitter.

Amino Acid Transport Systems, Acidic↗
PubMed2005

Use of surface affinity enrichment and cryo-embedding to prepare in vitro reconstituted mitotic chromosomes for EM tomography.

We present a novel preparation method for studies of in vitro reconstituted mitotic chromosomes from Xenopus laevis egg extracts. This method involves a gentle adsorption of chromosomes from the extracts using surface affinity enrichment, followed by plunge freezing, freeze-substitution and cryo-embedding before examination by EM tomography. For comparison, chromosomes were also prepared by a conventional method, which included immobilization of chromosomes in agarose and a room-temperature dehydration/embedding protocol. Three-dimensional reconstructions showed that samples prepared with the new method have a greater interconnectivity of sub-structural features and a higher compaction ratio together with an apparently less perturbed chromatin structure than those prepared using the conventional approach. The implications of the new method for the preparation of other difficult samples and additional application possibilities are discussed.

Animals↗
PubMed2005

NOSIP and its interacting protein, eNOS, in the rat trachea and lung.

Endothelial nitric oxide synthase (eNOS), the major nitric oxide (NO)-generating enzyme of the vasculature, is regulated through multiple interactions with proteins, including caveolin-1, Hsp90, Ca2+-calmodulin, and the recently discovered eNOS-interacting protein, NOSIP. Previous studies indicate that NOSIP may contribute to the intricate regulation of eNOS activity and availability. Because eNOS has been shown to be abundantly expressed in the airways, we determined the expression and cellular localization of NOSIP in rat trachea and lung by RT-PCR and immunohistochemistry and examined the interaction of NOSIP with eNOS in lung by coimmunoprecipitation. In tracheal epithelium and lung, NOSIP mRNA expression was prevalent, as shown by RT-PCR, and the corresponding protein interacted with eNOS, as demonstrated by coimmunoprecipitation. Using immunohistochemistry, we found both NOSIP and eNOS immunoreactivity in ciliated epithelial cells of trachea and bronchi, while Clara cells showed immunoreactivity for NOSIP only. NOSIP and eNOS were present in vascular and bronchial smooth muscle cells of large arteries and airways, whereas endothelial cells, as well as bronchiolar and arteriolar smooth muscle cells, exclusively stained for NOSIP. Our results point to functional role(s) of NOSIP in the control of airway and vascular diameter, mucosal secretion, NO synthesis in ciliated epithelium, and, therefore, of mucociliary and bronchial function.

Amino Acid Sequence↗
PubMed2004

Population coding of orientation in the visual cortex of alert cats--an information theoretic analysis.

We studied the encoding of stimulus orientation in the visual cortex of alert animals using information theory methods. Based on a labeled-line code, the encoding of orientation was mostly synergistic and only few pairs coded redundant. The synergy contributed about 20% of the information and was strongest for sites with distinct tuning curves. A recently proposed decomposition of synergy revealed that redundancy introduced by common tuning preferences is more than just compensated by noise correlations which mostly contributed synergistically. Based on a pooled response code, the contribution of noise correlations diminished resulting in a severe information loss. Thus, to operate economically, cortical neurons should either employ a labeled-line code or, if using pooled responses, be highly selective in choosing afferents.

Animals↗
PubMed2004

High-order events in cortical networks: a lower bound.

It is commonly believed that information processing in cortical networks involves the collective spiking activity of neuronal assemblies. Nevertheless, due to current technical limitations in multielectrodes recording methods, it is not possible to tackle this issue with direct experimental measurements. In this study we simulate spiking activity of large ensembles of cells focusing on the temporal correlation properties of the neuronal dynamics, and demonstrate that transient, fast synchronization of large groups of cells is a natural phenomenon of the cortical activity. To prove this result we use a statistical approach (based on combinatorics), and knowledge derived from a previous research work [A. Benucci et al., Phys. Rev. E 68, 041905 (2003)]. We quantify the degree of synchronous activity by computing a lower bound for the fraction of cells participating in fast (few milliseconds) synchronous events. Finally we discuss the implications of the results found in terms of cortical coding mechanisms.

Action Potentials↗
PubMed2004

A comparison of hemodynamic and neural responses in cat visual cortex using complex stimuli.

We compare fMRI-BOLD responses in anesthetized cats with local field potentials (LFPs), aggregate high-frequency responses (analog-Mua) and spiking activity recorded in primary and higher visual cortex of alert animals. The similarity of the activations in these electrophysiological signals to those in the BOLD is quantified by counting recording sites where different stimuli elicit the same relative activation as in the imaging experiments. Using artificial stimuli, a comparison of BOLD and LFP strongly depends on the frequency range used. Stimulating with complex or natural stimuli reduces this frequency dependence and yields a good match of LFP and BOLD. In general, this match is best between 20 and 50 Hz. The measures of high-frequency activity behave qualitatively different: the responses of the analog-Mua match those of the LFP; the spiking activity shows a low concordance with the BOLD signal. This dissociation of BOLD and spiking activity is most prominent upon stimulation with natural stimuli.

Animals↗