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PubMed1995

A computational model for signal processing by the dorsal cochlear nucleus. I. Responses to pure tones.

Much information is available on the anatomical organization and neurophysiological properties of the major cell types in the dorsal cochlear nucleus (DCN). The complicated response properties of individual cells and units in the DCN indicate that substantial information processing already occurs at the level of the DCN. A large number of connectional hypotheses have been put forward to explain various aspects of the response characteristics of DCN cells, but many of the consequences of these hypotheses have not been investigated quantitatively. In this paper, we investigate these hypotheses by constructing and testing mathematical and computational models and compare our results to those of previous modeling studies. The simplest versions of our models include auditory nerve (AN) fibers, type II cells (inhibitory interneurons) and type IV cells (fusiform and giant cells). The model response maps, i.e., the pattern of output of model type IV cells, generated by the simplest model have some but not all the features of the experimental response maps of type IV neurons. In particular, the excitatory region which occurs at best frequency is not isolated and the excitatory region at low frequencies and high amplitude is narrower than observed. Since experimental evidence exists that some of the connections between these cell types are divergent or convergent across adjacent isofrequency sheets, the effect of such convergence and divergence was then investigated. Response maps so obtained reproduce many of the qualitative features of the experimental maps. Enlargement of the model by including inhibitory interneurons (e.g., stellate cells) that receive convergent input from AN fibers and which inhibit type II cells results in the generation of response maps that, with some variations in connectional patterns and physiological properties of neurons, match most of the essential features seen in the large variety of experimental maps obtained from the cat DCN.

Animals↗

PubMed2003

A protein interaction map of Drosophila melanogaster.

Drosophila melanogaster is a proven model system for many aspects of human biology. Here we present a two-hybrid-based protein-interaction map of the fly proteome. A total of 10,623 predicted transcripts were isolated and screened against standard and normalized complementary DNA libraries to produce a draft map of 7048 proteins and 20,405 interactions. A computational method of rating two-hybrid interaction confidence was developed to refine this draft map to a higher confidence map of 4679 proteins and 4780 interactions. Statistical modeling of the network showed two levels of organization: a short-range organization, presumably corresponding to multiprotein complexes, and a more global organization, presumably corresponding to intercomplex connections. The network recapitulated known pathways, extended pathways, and uncovered previously unknown pathway components. This map serves as a starting point for a systems biology modeling of multicellular organisms, including humans.

Animals↗

PubMed2006

Formation of glomerular maps in the olfactory system.

Sensory perception relies on the decoding of external stimuli into an internal neuronal representation, which requires precise connections between the periphery and the brain. In the olfactory system the axons of chemosensory neurons with the same odorant receptor coalesce into common glomeruli in the olfactory bulb, forming a receptor-topic map. The creation of this map begins prenatally when axons navigate towards the bulb, resort in a receptor-specific manner and terminate in a broad area interdigitated with other axon populations; distinct glomeruli form postnatally. While the initial process of glomerulization requires mainly molecular determinants, activity-dependent processes lead to a refinement of glomerular organization.

Animals↗

PubMed2003

Atrial tachycardia arising from an epicardial site with venous connection between the left superior pulmonary vein and superior vena cava.

We describe a case of atrial tachycardia originating from an epicardial site with a venous connection between the left superior pulmonary vein (LSPV) and superior vena cava (SVC). Initial endocardial mapping with multiple electrodes catheters demonstrated early endocardial activation at both the SVC and LSPV. However, radiofrequency applications at the SVC failed to terminate the atrial tachycardia. With three-dimensional electroanatomic mapping, the earliest endocardial activation was found to be in the left atrial appendage (LAA). However, radiofrequency energy applications at multiple sites in the LAA resulted in only transient termination of the tachycardia. A left atrial angiogram demonstrated a venous connection between the LSPV and SVC, overlying the LAA. An application of radiofrequency energy with a saline-irrigated ablation catheter delivered at the earliest activation site in the LAA terminated the tachycardia. The tachycardia did not recur during 18-month follow-up.

Abnormalities, Multiple↗

PubMed2002

Three-dimensional map of a plant V-ATPase based on electron microscopy.

V-ATPases pump protons into the interior of various subcellular compartments at the expense of ATP. Previous studies have shown that these pumps comprise a membrane-integrated, proton-translocating (V(0)), and a soluble catalytic (V(1)) subcomplex connected to one another by a thin stalk region. We present two three-dimensional maps derived from electron microscopic images of the complete V-ATPase complex from the plant Kalanchoë daigremontiana at a resolution of 2.2 nm. In the presence of a non-hydrolyzable ATP analogue, the details of the stalk region between V(0) and V(1) were revealed for the first time in their three-dimensional organization. A central stalk was surrounded by three peripheral stalks of different sizes and shapes. In the absence of the ATP analogue, the tilt of V(0) changed with respect to V(1), and the stalk region was less clearly defined, perhaps due to increased flexibility and partial detachment of some of the peripheral stalks. These structural changes corresponded to decreased stability of the complex and might be the initial step in a controlled disassembly.

Adenylyl Imidodiphosphate↗

PubMed1985

Dimer ribbons in the three-dimensional structure of sarcoplasmic reticulum.

The three-dimensional structure of scallop sarcoplasmic reticulum membranes has been determined from electron micrographs of two classes of stain-filled tubules by helical reconstruction methods. These structures are characterized by dimer ribbons of Ca2+-ATPase molecules running diagonally around the tube wall. Deep right-handed grooves separate the ribbons. The elongated, curved units of the dimer (approximately 95 A long in the radial direction; 60 to 70 A axially, and about 30 A wide) are displaced axially by approximately 34 A and are connected at their outer ends by a bridge running nearly parallel to the tube axis. The monomers make a second contact at their inner ends. Adjacent units with the same orientation form a strong contact that is responsible for the ribbon appearance. Comparison of tubules of different diameter shows that one set of connections between the dimer ribbons is conserved: the inner ends of axially displaced dimers appear to make contact along a left-handed path almost perpendicular to the major grooves. The lipid bilayer cannot be clearly identified. The two-dimensional map obtained from flattened tubules is consistent with the three-dimensional reconstruction in showing dimer ribbons connected by a weak contact across the grooves, strongly resembling the inter-dimer bond observed in three dimensions. The two-dimensional map shows a 2-fold axis relating units of the dimer, but the three-dimensional tubes show a slight axial polarity that may arise from the presence of proteins other than the Ca2+-ATPase.

Animals↗

PubMed2001

Homo- and heterooligomeric SNARE complexes studied by site-directed spin labeling.

SNARE (soluble NSF acceptor protein receptor) proteins are thought to mediate membrane fusion by assembling into heterooligomeric complexes that connect the fusing membranes and initiate the fusion reaction. Here we used site-directed spin labeling to map conformational changes that occur upon homo- and heterooligomeric complex formation of neuronal SNARE proteins. We found that the soluble domains of synaptobrevin, SNAP-25, and syntaxin 1 are unstructured. At higher concentrations, the SNARE motif of syntaxin 1 forms homooligomeric helical bundles with at least some of the alpha-helices aligned in parallel. In the assembled SNARE complex, mapping of thirty side chain positions yielded spectra which are in good agreement with the recently published crystal structure. The loop region of SNAP-25 that connects the two SNARE motifs is largely unstructured. C-terminal truncation of synaptobrevin resulted in complexes that are completely folded N-terminal of the truncation but become unstructured at the C-terminal end. The binary complex of syntaxin and SNAP-25 consists of a parallel four helix-bundle with properties resembling that of the ternary complex.

Amino Acid Substitution↗

PubMed2004

Spatial distribution of functional superficial-deep connections in the adult ferret superior colliculus.

Numerous studies have identified connections between the superficial visual and deeper multisensory layers of the superior colliculus (SC), but the functional distribution of the superficial-deep projection has not been mapped. This question was assessed in the present study using extracellular electrophysiological stimulation and recording techniques. In vitro slices from adult ferrets were used to functionally map the rostro-caudal, medio-lateral, and dorso-ventral distribution of these superficial-deep connections. For each coronal (n=6) or parasagittal (n=10) slice, single and multi-unit responses to electrical stimulation of a point in the superficial layers were systematically recorded at different locations along a grid (approximately 300 microm intervals) across the slice. Recording sites with similar activation thresholds were grouped on the histological reconstruction of each slice to plot the functional access of superficial stimulation site to the deeper layers. Low intensity stimulation (defined as a current threshold < or =75 microA) activated areas of the subjacent intermediate layers in most cases (75%; 12/16). Higher intensity stimuli (> 75-600 microA) accessed larger areas which, in 50% of the slices, extended into the deepest layers of the SC. However, regardless of the rostro-caudal or medio-lateral position of the superficial layer stimulation site, the proportion of the deeper layers activated remained remarkably constant, although the volume of activated deep layer tissue was shifted in each case toward the central regions of the SC. This last observation argues against the precise alignment of the superficial and deep layer visual maps, suggesting instead that the arrangement of the superficial layer projection may more closely relate to the organization of deep layer auditory and/or somatosensory representations.

Action Potentials↗

PubMed1999

Finite-connectivity systems as error-correcting codes.

We investigate the performance of parity check codes using the mapping onto Ising spin systems proposed by Sourlas [Nature (London) 339, 693 (1989); Europhys. Lett. 25, 159 (1994)]. We study codes where each parity check comprises products of K bits selected from the original digital message with exactly C checks per message bit. We show, using the replica method, that these codes saturate Shannon's coding bound for K-->infinity when the code rate K/C is finite. We then examine the finite temperature case to assess the use of simulated annealing methods for decoding, study the performance of the finite K case, and extend the analysis to accommodate different types of noisy channels. The connection between statistical physics and belief propagation decoders is discussed and the dynamics of the decoding itself is analyzed. Further insight into new approaches for improving the code performance is given.

Journal Article↗

PubMed1994

Competition and position-dependent targeting in the development of the Drosophila R7 visual projections.

The R7 photoreceptor neuron projections form a retinotopic map in the medulla of the Drosophila optic lobe. The more inner photoreceptors mutation, an allele of gap1, results in the differentiation of excess R7s in the eye, whose axons invade the brain and establish functional connections. We have used this hyperinnervation phenotype to explore the roles of photoreceptor-target regulation, competitive interactions, and chemoaffinity in map formation. We show that the extra axons are supported in a wild-type brain, with all R7s from a single ommatidium sharing a single termination site, and thus there is no evidence that the target regulates the size of the presynaptic population. In mosaic eyes, in which ommatidia containing extra R7s are surrounded by ommatidia lacking all R7 cells, R7 axons still target to appropriate retinotopic locations in a largely empty R7 terminal field. Axons at the edges of the projection, however, send collaterals into vacant areas of the field, suggesting they are normally restrained to share single termination sites by competitive interactions. In contrast, no sprouts are seen when the vacant sites are juxtaposed with singly innervated sites. In the third instar, R7 and R8 axons transiently display halos of filopodia that overlap adjacent terminals and provide a means to assess occupancy at adjacent sites. Finally, in sine oculis larvae in which only a small number of ommatidia develop, the R7/R8 axons target to predicted dorsoventral portions of the medulla despite the absence of their neighbors, suggesting that position in the eye field determines their connectivity in the brain. We suggest that the mechanisms used to set up this insect map are formally similar to strategies used by vertebrates. The availability of a genetic model for these events should facilitate studies aimed at understanding the molecular bases of retinotopic map development.

Animals↗

PubMedDate not supplied

A dynamical model of fast cortical reorganization.

In this work we study the connection between some dynamic effects at the synaptic level and fast reorganization of cortical sensory maps. By using a biologically plausible computational model of the primary somatosensory system we obtained simulation results that can be used to relate the dynamics of the interactions of excitatory and inhibitory neurons to the process of somatotopic map reorganization immediately after peripheral lesion. The model consists of three regions integrated into a single structure: tactile receptors representing the glabrous surface of the hand, ventral posterior lateral nucleus of the thalamus and area 3b of the primary somatosensory cortex, reproducing the main aspects of the connectivity of these regions. By applying informational measures to the simulation results of the dynamic behavior of AMPA, NMDA and GABA synaptic conductances we draw some conjectures about how the several neuronal synaptic elements are related to the initial stage of the digit-induced reorganization of the hand map in the somatosensory cortex.

Animals↗

PubMedDate not supplied

Pattern formation and cortical maps.

The response selectivities of neurons in adult primary sensory cortices depend on intricate patterns of synaptic connections; these selectivities are arranged over cortex in equally rich fashion. Characterising these patterns, and particularly the activity-dependence (and independence) of their developmental trajectories, has been a major task for experimental and theoretical neuroscience. Here, we describe and analyse a paradigmatic algorithm for activity-dependent development of the refinement and generation of neuronal selectivities, and relate it to some of the wealth of suggestions in the literature.

Animals↗

PubMed2006

Connected populations for detecting quantitative trait loci and testing for epistasis: an application in maize.

Quantitative trait loci (QTL) detection experiments have often been restricted to large biallelic populations. Use of connected multiparental crosses has been proposed to increase the genetic variability addressed and to test for epistatic interactions between QTL and the genetic background. We present here the results of a QTL detection performed on six connected F(2) populations of 150 F(2:3) families each, derived from four maize inbreds and evaluated for three traits of agronomic interest. The QTL detection was carried out by composite interval mapping on each population separately, then on the global design either by taking into account the connections between populations or not. Epistatic interactions between loci and with the genetic background were tested. Taking into account the connections between populations increased the number of QTL detected and the accuracy of QTL position estimates. We detected many epistatic interactions, particularly for grain yield QTL (R(2) increase of 9.6%). Use of connections for the QTL detection also allowed a global ranking of alleles at each QTL. Allelic relationships and epistasis both contribute to the lack of consistency for QTL positions observed among populations, in addition to the limited power of the tests. The potential benefit of assembling favorable alleles by marker-assisted selection are discussed.

Epistasis, Genetic↗

PubMed1997

Regional differences of callosal connections in the granular zones of the primary somatosensory cortex in rats.

The primary somatosensory cortex (SI) in rats is cytoarchitectonically divided into three zones: the granular, peri-, and dysgranular zones. To examine callosal connections in the granular zone that bears representation of the body somatosensory map, the distribution of lectin-conjugated horse-radish peroxidase labeis was explored in the right SI after single or multiple injections into the granular zone of the left SI. After injections in the upper and lower law regions, many labeled cell bodies and dense terminal labeling were found in the regions homotopical to the injection sites. Both kinds of labels were densely seen in layers II-III and V, less densely in layer VI. Densely labeled terminals were also observed in layer I. In layer IV, many terminals and a few cell bodies were labeled in the septa, while labeling inside the barrels was sparse or absent. After injections in other regions, i.e., those representing the facial whiskers, fore- and hindlimbs, or trunk in the granular zone, labeled callosal cell bodies and terminals were sparse or absent, except in the septa of the posteromedial barrel subfield representing the facial whiskers. The results clearly show that the density of callosal connection in the granular zone differs in different subfields, and that at least the jaw regions in the granular zones of both hemispheres are directly interconnected, in contrast to the previous assumption that only the dysgranular zone mediates information transmission between the granular zones of both sides.

Animals↗

PubMed1967