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M J Wright

Publications and source records attributed to M J Wright.

At least 127 records · Page 7Linked to original sources

The outer disinhibitory surround of the retinal ganglion cell receptive field.

1. There is an outer disinhibitory zone surrounding the classical inhibitory surround of the retinal ganglion cell receptive field.2. The disinhibitory surround is strong and narrow in ;sustained' cells but weak and laterally spread in ;transient' cells.3. The disinhibitory surround can be demonstrated using a black spot as a probing stimulus as well as by a white spot, and is therefore not an artifact of scattered light.4. Stimulation with a light spot in the disinhibitory zone gives an increase in firing to ;stimulus on' in on-centre cells and to ;stimulus off' in off-centre cells.5. The disinhibitory surround may be revealed by plotting the latency of the first spike discharge following stimulation against position in the receptive field. The disinhibitory zone shows a decrease in latency to the centre-type stimulus.6. The disinhibitory surround may be revealed by plotting the threshold intensity of a spot against position in the receptive field. It is thus a feature of the sensitivity gradients of both ;transient' and ;sustained' cells.7. Using two spots, one at the centre of the receptive field and the other at varying distances from the receptive field centre, dynamic interactions between the centre, inhibitory and disinhibitory zones are demonstrated. A spot presented in the disinhibitory zone causes an enhancement of the centre response when flashing in phase with the centre spot, while it causes inhibition of the centre response when presented 180 degrees out of phase.8. A scheme for the anatomical basis of the disinhibitory surround is proposed, and the relation of disinhibition to the spatial transfer characteristics of the visual pathways is discussed.

Action Potentials↗

Receptive field organization of 'sustained' and 'transient' retinal ganglion cells which subserve different function roles.

1. Post-stimulus histograms were obtained from ;sustained' and ;transient' retinal ganglion cells for receptive field plots using a light spot with square-wave modulation of intensity, and of variable intensity and area. Fundamental differences in their receptive field organization in time and space were revealed.2. In ;sustained' cells, excitation consists of ;transient' and ;sustained' components and the ratio of transient/sustained components remains constant at a given retinal locus for a wide range of intensities. The transient component becomes proportionally larger towards the periphery of the receptive field. This rule is also applicable for the inhibitory and disinhibitory surround. In ;transient' cells, however, there is no true ;sustained' component, but some cells produce a double peaked transient post-stimulus histogram at the R.F. centre when high flux stimuli are used, while others show a single peak transient response. The magnitude and shape of transient responses changes with intensity as well as with location in the receptive field.3. The sensitivity gradients of ;sustained' and ;transient' cells show consistent differences in shape. The mean slope of the sensitivity gradients of a sample of ;sustained' cells was 10 times that of a sample of ;transient' cells. The sensitivity gradient of ;sustained' cells shows a distinct surround region where the inhibitory mechanism is more sensitive, while that of ;transient' cells usually does not, owing to an extensive ;tail' on the sensitivity gradient of the centre mechanism, which overlaps the surround.4. Ricco's Law also holds for the centre mechanism of ;transient' cells. Non-linear summation occurs at supra-threshold levels, and when the surround mechanisms are involved.5. Supra-optimal stimuli give a saturation of the response in both ;transient and ;sustained' cells. This saturation is associated with a decrease of latency in ;transient' cells, but not in ;sustained' cells.6. The latency of retinal ganglion cells is determined by both stimulus and background flux. The effect of the background is negligible except at low values of stimulus flux, where its effect may be analysed primarily in terms of its effect on the incremental threshold.7. The latency to stimulation with a standard small spot (25-27') at the receptive field centre is shorter for ;sustained' cells than for ;transient' cells; this latency difference being related to the greater sensitivity of the ;sustained' cells to stimuli of this size. Differences in conduction time along ;transient' and ;sustained' pathways to the lateral geniculate nucleus (LGN) and cortex were estimated, and it is concluded that despite the latency difference noted above, a response to a stimulus which is optimal for a ;transient' cell reaches the cortex faster than the response to a stimulus which is optimal for a ;sustained' cell.8. The above results together with previous evidence available suggest that for most stimuli, centre and surround mechanisms are activated simultaneously and algebraically summed by a single linear stage in ;sustained' cells. In ;transient' cells, although the centre excitation and surround inhibition pools are also spatially co-extensive, they summate and interact in time and space with a greater complexity.9. Differences in the receptive field organization of ;sustained' and ;transient' cells may reflect their different functional roles in vision: (1) analysis of spatial contrast and form recognition (;sustained' cells), and (2) fast detection of objects entering visual space to cause orientation responses (;transient' cells).

Animals↗

In vivo myocardial gene transfer: optimization, evaluation and direct comparison of gene transfer vectors.

The purpose was to determine the relative efficiency, toxicity and duration of expression following gene delivery by intramyocardial injection of naked DNA, naked DNA complexed to cationic liposomes, naked DNA complexed to cationic liposomes with integrin-targetting peptide, recombinant (E1-/E3-) adenovirus, recombinant adeno-associated virus and recombinant (ICP27-) herpes simplex virus. All vectors incorporated a LacZ reporter driven by a promoter containing the hCMV-IE promoter/enhancer. Efficiency was scored by counting positive cells in five standard microscopic sections harvested from the left ventricular apex. Rabbit hearts (n = 100) were examined from 2 to 56 days after injection. Uncomplexed and complexed naked DNA were very inefficient with less than one positive cell visible per heart. The viral vectors all resulted in robust gene expression with adenovirus being the most efficient by at least one order of magnitude before 21 days. However, despite disparate titres, the efficiency beyond 21 days of adenovirus and adeno-associated virus were comparable. In contrast to adeno-associated virus, both adenovirus and herpes-simplex virus were associated with a marked inflammatory response. Despite reporter gene activity appearing only after 21 days, adeno-associated virus shows comparative promise as a myocardial gene delivery vector.

Adenoviridae↗