PubMed Health⌕ Search

Biomedical subjects

David J Willshaw

Publications and source records attributed to David J Willshaw.

2 recordsLinked to original sources

The cingulate as a catalyst region for global dysfunction: a dynamical modelling paradigm.

The anterior cingulate (AC) often exhibits both structural and functional abnormalities in affective disorders. Neither the cause for this vulnerability nor its effect on behaviour is known. Due to its extensive connectivity, minor output changes from the AC may exert widespread consequences. A causal model describing coupling coefficients (effective connectivity) among several brain regions in healthy subjects performing a memory task inspired our work. This stationary causal analysis provides a theoretical framework for our nonlinear dynamical models. We tested the effects of global and local perturbations upon stability of a systems-level neural network of interconnected brain regions. Interactions between regions, represented by path coefficients, were modelled using connectivity matrices. We found that both characteristic behaviour and response to perturbation differed in networks representing perceptual matching and long-delay conditions. Owing to the highly interconnected character of the networks, activation of a few areas was sufficient to trigger characteristic patterns of behaviour. However, only perturbation of key regions resulted in global dysfunction. Likewise, recovery of function was possible by increasing output from some, but not all, regions. We suggest for this recovery to be context specific, conditional on the task, integrity of other regions and global properties such as neuronal excitability.

Biological Clocks↗

Influence of cell fate mechanisms upon retinal mosaic formation: a modelling study.

Many types of retinal neurone are arranged in a spatially regular manner so that the visual scene is uniformly sampled. Several mechanisms are thought to be involved in the development of regular cellular positioning. One early-acting mechanism is the lateral inhibition of neighbouring cells from acquiring the same fate, mediated by Delta-Notch signalling. We have used computer modelling to test whether lateral inhibition might transform an initial population of undifferentiated cells into more regular populations of two types of differentiated cells. Initial undifferentiated cells were positioned randomly, subject only to a minimal distance constraint. Each undifferentiated cell then acquired either primary or secondary fate using one of several lateral inhibition mechanisms. Mosaic regularity was assessed using the regularity index and the packing factor. We found that for irregular undifferentiated mosaics, the arrangement of resulting primary (but not secondary) fate cells was more regular than in the initial undifferentiated population. However, for regular undifferentiated mosaics, no further increases in the regularity of the primary fate mosaics were observed. We have used this model to test the specific hypothesis that on- and off-centre retinal ganglion cells emerge from an initial, irregular undifferentiated population of ganglion cells. Lateral inhibition can subdivide an initially irregular population into two types of cell that are mildly regular. However, lateral inhibition alone is insufficient to produce mosaics of the same regularity as observed experimentally. Likewise, and in contrast to earlier reports, cell death alone is insufficient to match the regularity of experimental mosaics. We conclude that lateral inhibition can transform irregular distributions into regular mosaics, upon which subsequent processes (such as lateral cell movement or cell death) can further refine mosaic regularity.

Animals↗