Faculty Bibliography

A large-scale computational model of a local patch of input layer 4 [Formula: see text] of the primary visual cortex (V1) of the macaque monkey, together with a coarse-grained reduction of the model, are used to understand potential effects of cortical architecture upon neuronal performance. Both the large-scale point neuron model and its asymptotic reduction are described. The work focuses upon orientation preference and selectivity, and upon the spatial distribution of neuronal responses across the cortical layer. Emphasis is given to the role of cortical architecture (the geometry of synaptic connectivity, of the ordered and disordered structure of input feature maps, and of their interplay) as mechanisms underlying cortical responses within the model. Specifically: (i) Distinct characteristics of model neuronal responses (firing rates and orientation selectivity) as they depend upon the neuron's location within the cortical layer relative to the pinwheel centers of the map of orientation preference; (ii) A time independent (DC) elevation in cortico-cortical conductances within the model, in contrast to a 'push-pull' antagonism between excitation and inhibition; (iii) The use of asymptotic analysis to unveil mechanisms which underly these performances of the model; (iv) A discussion of emerging experimental data. The work illustrates that large-scale scientific computation--coupled together with analytical reduction, mathematical analysis, and experimental data, can provide significant understanding and intuition about the possible mechanisms of cortical response. It also illustrates that the idealization which is a necessary part of theoretical modeling can outline in sharp relief the consequences of differing alternative interpretations and mechanisms--with final arbiter being a body of experimental evidence whose measurements address the consequences of these analyses

Proteoglycans are cell surface and extracellular matrix molecules to which long, unbranched glycosaminoglycan side chains are attached. Heparan sulphate, a type of glycosaminoglycan chain, has been proposed as a co-factor necessary for signalling by a range of growth factors. Here we provide evidence that loss of 2-O-sulphation in heparan sulphate leads to a significant reduction in cell proliferation in the developing cerebral cortex. The gene encoding heparan sulphate 2-sulphotransferase (Hs2st) is expressed in embryonic cortex and histological analysis of mice homozygous for a null mutation in Hs2st indicated a reduction in the thickness of the embryonic cerebral cortex. Using 5'-bromodeoxyuridine (BrdU) incorporation assays we found a reduction of approximately 40% in labelling indices of cortical precursor cells at E12. Comparison of the fates of cortical cells born on E13 and E15 in Hs2st(-/-) mutant and wildtype littermate embryos revealed no differences in the pattern of cell migration. Our findings suggest a critical role for 2-O-sulphation of heparan sulphate proteoglycan (HSPG) in regulating cell proliferation during development of the cerebral cortex, perhaps through the modulation of cellular responses to growth factor signalling

BACKGROUND: The purpose of this work was to develop methods for successful cryopreservation of human oocytes. METHODS: Two cryopreservation procedures were used. Method 1 involved use of 1.5 mol/l propanediol (PrOH)-0.1 mol/l sucrose with medium containing sodium (Na) as cryoprotectant medium, seeding at -7 degrees C, and stepwise dilution of cryoprotectant post-thaw. Method 2 used Na-depleted media with 1.5 mol/l PrOH-0.2 mol/l sucrose for freezing, seeding at -6 degrees C, and use of high sucrose (0.5 and 0.2 mol/l) for cryoprotectant removal. RESULTS: The first method was used in seven patients, and gave poor (12.3%) survival results and no pregnancies. The second method was used in 15 patients (16 cycles), and yielded good survival and fertilization rates (74.4 and 59% respectively), with four pregnancies and five healthy infants born to 11 women receiving an embryo transfer. CONCLUSIONS: Using Na-depleted media along with other alterations in freezing and thawing procedures, human oocyte cryopreservation can provide excellent survival and pregnancy rates

Downstream development is a term encompassinga variety of effects relating to the propagation of storm systems at midlatitude. We investigate a mechanism behind downstream development and study how wave propagation is affected by varying several physical parameters. We then develop a multiple scales modulation theory based on processes in the leading edge of propagating fronts to examine the effect of nonlinearity and weak variation in the background flow. Detailed comparisons are made with numerical experiments for a simple model system

This paper reports on the consequences of large, activity dependent, synaptic conductances for neurons in a large-scale neuronal network model of the input layer 4Calpha of the Macaque primary visual cortex (Area V1). This high conductance state accounts for experimental observations about orientation selectivity, dynamics, and response magnitude (D. McLaughlin et al. (2000) Proc. Natl. Acad. Sci. USA 97: 8087-8092), and the linear dependence of Simple cells on visual stimuli (J. Wielaard et al. (2001) J. Neuroscience 21: 5203-5211). The source of large conductances in the model can be traced to inhibitory corticocortical synapses, and the model's predictions of large conductance changes are consistent with recent intracellular measurements (L. Borg-Graham et al. (1998) Nature 393: 369-373; J. Hirsch et al. (1998) J. Neuroscience 15: 9517-9528; J.S. Anderson et al. (2000) J. Neurophysiol. 84: 909-926). During visual stimulation, these conductances are large enough that their associated time-scales become the shortest in the model cortex, even below that of synaptic interactions. One consequence of this activity driven separation of time-scales is that a neuron responds very quickly to temporal changes in its synaptic drive, with its intracellular membrane potential tracking closely an effective reversal potential composed of the instantaneous synaptic inputs. From the effective potential and large synaptic conductance, the spiking activity of a cell can be expressed in an interesting and simplified manner, with the result suggesting how accurate and smoothly graded responses are achieved in the model network. Further, since neurons in this high-conductance state respond quickly, they are also good candidates as coincidence detectors and burst transmitters

We present a reduction of a large-scale network model of visual cortex developed by McLaughlin, Shapley, Shelley, and Wielaard. The reduction is from many integrate-and-fire neurons to a spatially coarse-grained system for firing rates of neuronal subpopulations. It accounts explicitly for spatially varying architecture, ordered cortical maps (such as orientation preference) that vary regularly across the cortical layer, and disordered cortical maps (such as spatial phase preference or stochastic input conductances) that may vary widely from cortical neuron to cortical neuron. The result of the reduction is a set of nonlinear spatiotemporal integral equations for 'phase-averaged' firing rates of neuronal subpopulations across the model cortex, derived asymptotically from the full model without the addition of any extra phenomological constants. This reduced system is used to study the response of the model to drifting grating stimuli-where it is shown to be useful for numerical investigations that reproduce, at far less computational cost, the salient features of the point-neuron network and for analytical investigations that unveil cortical mechanisms behind the responses observed in the simulations of the large-scale computational model. For example, the reduced equations clearly show (1) phase averaging as the source of the time-invariance of cortico-cortical conductances, (2) the mechanisms in the model for higher firing rates and better orientation selectivity of simple cells which are near pinwheel centers, (3) the effects of the length-scales of cortico-cortical coupling, and (4) the role of noise in improving the contrast invariance of orientation selectivity

To address finite-size effects in the use of the decay mutual information to characterize spatiotemporal chaotic dynamics, we modify the dispersion of the nonlinear Schrodinger equation to obtain a model system for which the number of unstable modes remains fired while the domain size increases. Our numerical study of the model system clearly establishes that spatiotemporal chaos arises in the presence of only two unstable modes. In this spatially extended system, the spatiotemporal chaos is characterized by chaotic dynamics in time and by an exponential decay in space of mutual information, with the decay rate becoming system-size independent in the large system-size limit. (C) 2001 IMACS. Published by Elsevier Science B.V. All rights reserved

Our objective is a realistic theory of the visual cortex that can explain the visual selectivity, dynamics, and the diversity of visual properties in cortical cell populations. To do this, we have studied a large-scale computational model of Macaque V1 (McLaughlin et al. 2000 PNAS) based on anatomy and physiology. The model consists of 4 hypercolumns of inhibitory and excitatory point neurons (a lattice of 128X128 neurons). The model's intra-cortical connectivity is nonspecific and isotropic. The spatial extent of cortical excitatory connections exceeds that of inhibitory connections, as indicated by anatomical data. Cells in the model are classified as Simple or Complex by the same index of linearity of spatial summation that has been used in physiology experiments. Previously we showed how Simple cells could exist in the model despite the non-linearity of the LGN input and of cortico-cortical excitation (Wielaard et al 2001 J. NS.)-through strong cortico-cortical inhibition, synaptic pooling of cell responses, and diversity in the arrangement of LGN On/Off subregions. Complex cells arise in the model by allowing for randomness in synaptic coupling strengths, which can increase the importance of network excitation, and randomness in the strength of LGN input. Also, there is a small population of neurons in the model that are intermediate, in linearity of summation, between Simple and Complex cells. Therefore, the model produces diversity and properties of cortical responses that are consistent with physiological observations in Macaque V1 (Ringach et al 2001 J. NS.)

In this article, we study numerically a one-dimensional model of dispersive wave turbulence. The article begins with a description of the model which we introduced earlier, followed by a concise summary of our previous results about it. In those previous studies, in addition to the spectra of weak turbulence (WT) theory, we also observed another distinct spectrum (the "MMT spectrum"). Our new results, presented here, include: (i) A detailed description of coexistence of spectra at distinct spatial scales, and the transitions between them at different temporal scales; (ii) The existence of a stable MMT front in k-space which separates the WT cascades from the dissipation range, for various forms of strong damping including "selective dissipation"; (iii) The existence of turbulent cycles in the one-dimensional model with focusing nonlinearity, induced by the interaction of spatially localized coherent structures with the resonant quartets of dispersive wave radiation; (iv) The detailed composition of these turbulent cycles - including the self-similar formation of focusing events (distinct in the forced and freely decaying cases), and the transport by the WT direct and inverse cascades of excitations between spatial scales. This one-dimensional model admits a very precise and detailed realization of these turbulent cycles and their components. Our numerical experiments demonstrate that a complete theory of dispersive wave turbulence will require a full description of the turbulent field over all spatial scales (including those of the forcing and dissipation), and over extremely long times (as the nonlinear turnover time becomes very long in the weakly nonlinear limit). And, in the focusing case, a complete theory must also incorporate the interaction of localized coherent structures with resonant radiation. (C) 2001 Elsevier Science B.V. All rights reserved