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Biomedical subjects

W R Levick

Publications and source records attributed to W R Levick.

At least 19 recordsLinked to original sources

Hypokalaemic episodic polymyopathy in cats fed a vegetarian diet.

A previously undocumented hypokalaemic condition with a cyclical nature, comprising acute bouts of polymyopathy followed by spontaneous recoveries, is described in the cat. Cats being fed a high protein vegetarian diet developed recurrent episodes of polymyopathy, characterised by ventroflexion of the head and neck, stiff forelimb gait, lateral head-resting and generalised muscle weakness. Plasma potassium concentrations (mean +/- standard deviation) were reduced from 3.28 +/- 0.33 mmol/l at the beginning of the experiment to 2.45 +/- 0.24 mmol/l during bouts of myopathy. This hypokalaemia was associated with increased creatine kinase activities indicative of muscle damage, and decreased urinary potassium concentrations, and was caused by insufficient dietary potassium. Cats that received the same diet supplemented with potassium did not develop hypokalaemic polymyopathy. Spontaneous recoveries of affected cats were not associated consistently with increases in plasma potassium concentrations. Plasma taurine concentrations decreased and glutamic acid increased markedly in all cats fed the experimental diet. There was no evidence of thiamin deficiency associated with the high glutamic acid intake. Veterinarians should be aware that hypokalaemic cats, and in particular those on potassium-deficient diets, may show cyclical disease with episodes of polymyopathy recurring after periods of spontaneous clinical recovery. This condition in cats may be a useful animal model for familial hypokalaemic periodic paralysis in humans.

Amino Acids

Nonlinear measurement and classification of receptive fields in cat retinal ganglion cells.

Originally, modeling of ganglion-cell responses in cat was based mainly on linear analysis. This is satisfactory for those cells in which spatial summation of excitation is approximately linear (X-cells) but it fails for Y-cells, where summation has strong nonlinear components. Others have shown the utility of using sinusoidal analysis to study harmonic and intermodulation nonlinearities in the temporal frequency domain. We have used Wiener-kernel analysis to obtain directly both temporal and spatial impulse responses and their nonlinear interactions. From these, we were able to predict accurately the responses that a counterphase modulated grating elicited in both X-cells and Y-cells. In addition, we show that the first-order responses can measure the two-dimensional spatial features of the receptive field with high resolution. Thus, nonlinear analysis of responses to white-noise stimuli may be sufficient to both classify and measure the receptive fields of many different types of ganglion cells.

Animals

Retinotopic organization in the dorsal lateral geniculate nucleus of the tammar wallaby (Macropus eugenii).

Electrophysiological recordings were made from 187 single cells in the tammar wallaby (Macropus eugenii) dorsal lateral geniculate nucleus (LGNd). The results show that it is topographically organized such that the superior visual field is represented dorsally, the inferior field is represented ventrally, the nasal visual field is represented caudally, and the temporal visual field is represented rostrally. The visual field of one eye ranges from -30 degrees nasal to +179 degrees temporal in azimuth and +73 degrees superior to -49 degrees inferior in elevation. Ganglion cells that had receptive field positions between -9 degrees and +179 degrees projected to the contralateral LGNd while the ganglion cells that projected to the ipsilateral LGNd had visual fields from 0 to +30 degrees. The binocular visual field extends 60 degrees in azimuth. This representation in the LGNd is expanded relative to the monocular representation. There is also an increased representation of the horizon in the temporal field corresponding to the visual streak of retinal ganglion cells. The binocular visual field is located where contralateral and ipsilateral laminae are shown to interdigitate by proline autoradiography. There are nine eye-specific laminae in the LGNd. Four receive afferents from the contralateral eye and five receive afferents from the ipsilateral eye. The lines of isoelevation are perpendicular to the coronal plane of section while the lines of isoazimuth are nearly parallel to the coronal plane. The lines of projection representing one visual direction are inferred to be perpendicular to the tangent of curvature of the laminae as in the LGNd of other mammals. The majority of cells (85%) recorded had on- or off-centre responses. On- and off-centre responses were not apparently segregated in the LGNd but segregation may not have been revealed by the single-unit recording technique.

Animals

Orientation bias of brisk-transient y-cells of the cat retina for drifting and alternating gratings.

Brisk-transient ganglion cells of the cat's retina were examined for orientation bias using two different stimuli: drifting gratings and alternating gratings, both of fixed contrast (50%) and fixed temporal frequency (2 Hz). Some cells were strongly biassed for both stimuli, some were not biassed for either while still others were strongly biassed for only one or other stimulus. The preferred orientations for the two types of grating tended to be the same, on average, but substantial differences were not uncommon. A systematic preference for radially-oriented gratings was evident when the stimulus was drifting but there was an additional preference for tangentially-oriented gratings when the stimulus was alternating. Orientation bias for drifting gratings often extended over a broad range of spatial frequencies and was maximum near the resolution limit. For alternating gratings, bias was evident only at the highest spatial frequencies. Results indicate that the arrangement of receptive field components responsible for linear and nonlinear kinds of behaviour may sometimes possess different axes of symmetry.

Animals

Spatial frequency characteristics of brisk and sluggish ganglion cells of the cat's retina.

Receptive fields of cat retinal ganglion cells were stimulated by a drifting sinusoidal luminance pattern of fixed (50%) contrast and the amplitude of the fundamental frequency component of response was determined as a function of spatial frequency. Frequency response functions for most cells were unimodal and skewed towards zero frequency when plotted on linear scales. At a fixed retinal location, cells of different classes had different frequency response functions. Heterogeneity within some of the classes could be largely removed by normalizing the axes, thus, revealing a common shape of function for the class. At a fixed retinal location, the maximum response obtained at each spatial frequency was always obtained from a cell of the brisk, rather than sluggish, classes. Spatial frequency resolution was highest for brisk-sustained cells and usually lowest for brisk transient cells.

Animals

Bimodal receptive fields of cat retinal ganglion cells.

Receptive fields of cat retinal ganglion cells were stimulated by a drifting, sinusoidal luminance pattern of fixed contrast. The amplitudes and phases of the harmonic components in the response were determined as a function of spatial frequency. For most cells, the graphs of response vs spatial frequency (when plotted on linear scales) were unimodal and skewed towards zero frequency for all stimulus orientations. However, some cells had bimodal frequency response functions when the stimulus was in the non-preferred orientation. These unusual cells also exhibited a sudden phase-reversal of pi radians which occurred at the frequency of the changeover between the two modes. Calculations based on the experimental data predicted two distinctly separate regions of high sensitivity within the receptive centres of such cells. A narrow bar stimulus was used to confirm that the receptive fields had, in effect, double centres.

Action Potentials

Performance of cat retinal ganglion cells at low light levels.

Responses of brisk-sustained cat retinal ganglion cells were examined using receiver operating characteristic (ROC) analysis. Stimuli were brief luminance changes superimposed upon a weak steady pedestal ranging from 27 to 47,000 quanta (507 nm) per second at the cornea. Overall quantum efficiencies of cells ranged up to approximately 13% and were compatible with previous estimates at absolute threshold. The main work was done on on-center cells, but a small sample of off-center units behaved similarly. Experimental ROC curves verified a set of qualitative predictions based on a theoretical treatment of performance, assuming that response variability resulted solely from quantum fluctuations. However, quantitative predictions were not fulfilled. The discrepancy could be resolved by postulating a source of added internal variance, R, the value of which could then be deduced from the experimental measurements. A ganglion cell model limited by a fixed amount of added variance from physiological sources and having access to a fixed fraction of incident quanta can account quantitatively for (a) slopes of ROC curves, (b) variation of detectability with magnitude of both increments and decrements, and (c) performance over a range of pedestal intensities. Estimates of the proportion of incident quanta used ranged up to 29% under some conditions, a figure approximately matching estimates of the fraction of corneal quanta that isomerize rhodopsin in the cat.

Animals

Astigmatic visual and deprivation in cat: behavioral, optical and retinophysiological consequences.

Kittens were deprived of clear vision in one eye only by +7D or -7D cylindrical lenses worn from eye opening until 7.5 months of age. Behavioral measurements subsequently demonstrated diminished acuity through the affected eye relative to the opposite control eye. However, single unit recordings at 3.5 years of age from retinal ganglion cells located within 1-11 degrees of the centre of the area centralis showed neither loss of grating resolution nor any abnormal orientation bias. Furthermore, the astigmatic rearing had minimal effect on the development of the cat's natural optics to the emmetropic state. The experiments indicate that the amblyopic defect induced by the cylindrical lenses occurs in the brain rather than the eye.

Age Factors

Analysis of orientation bias in cat retina.

1. Responses of cat retinal ganglion cells to a drifting sinusoidal grating stimulus were measured as a function of the grating orientation and spatial frequency.2. The response at fixed frequency and contrast varied with orientation in the manner of a cosine function. A new measure was introduced to quantify this orientation bias in the response domain on an absolute scale of 0-100%. Under experimental conditions designed to maximize the effect, the mean bias for 250 cells was 16% and the range was 0-46%. In 70% of cells there was significant bias.3. Orientation bias varied with spatial frequency and was maximal near the high-frequency limit. The majority of biassed cells preferred the same orientation at high and low frequencies but in some cells a reversal occurred: the orientation which gave maximum response at high frequencies gave minimum response at low frequencies. The greatest variation of cut-off frequency with orientation was (2/3) octave.4. Orientation bias was due to neural, not optical, factors. Nevertheless, the phenomenon could often be imitated by deliberately introduced optical astigmatism of up to 4 dioptres for brisk-sustained units and over 10 dioptres for brisk-transient units.5. The grating orientation preferred by cells varied systematically with position in the visual field. The central tendency was for the grating which yielded maximum response to lie parallel to the line joining the cell to the area centralis. This generalization failed for units within 2 degrees of the centre of the area centralis.6. Analysis of orientation bias indicates a functional asymmetry of receptive fields such that the centre mechanism, and sometimes also the surround mechanism, is elongated along the line joining cell to area centralis.

Animals

Rabbit retinal ganglion cells. Receptive field classification and axonal conduction properties.

The classification of concentrically organized receptive fields of rabbit retinal ganglion cells was extended along similar lines to that in the cat by distinguishing brisk and sluggish classes and then sustained and transient types of each. Quantitative measures of responsiveness to stationary and to moving stimuli revealed characteristic features which distinguished these classes. Brisk-transient and brisk-sustained classes are not as distinct from each other as in the cat: centre size distributions overlapped almost completely and there was also substantial overlap of axonal conduction properties whether expressed in terms of latency or conduction velocity between two central stimulus sites. Representatives of every class of rabbit ganglion cells sent axons to the superior colliculus.

Action Potentials

Orientation bias of cat retinal ganglion cells.

Kuffler described the receptive fields of cat retinal ganglion cells as having a concentric arrangement. This has usually been taken to mean that they are approximately circular in form (see, for example, ref. 2). Hammond tested the circularity of the centre component of receptive fields by plotting a contour of isosensitivity to a small flashed spot. He concluded that centres were often ellipitical (average ratio of major to minor axis 1.23) and that more than 50% of the recorded cells had the major axis oriented within /+- 20 degrees of the horizontal. Such data are important for discussions of the neurophysiological basis of the 'oblique effect' (reduced visibility for periodic grating patterns when oriented away from the vertical or horizontal) observed in psychophysical experiments on humans because subcortical units are often assumed to be orientationally unbiased. Orientation selectivity is a prominent attribute of visual cortical neurones so analysis has usually emphasized the distribution of orientation selectivity at that level. The results presented here redirect attention to the retinal level since they reveal a previously unsuspected systematic relation between orientation bias of ganglion cells and their location relative to the area centralis.

Action Potentials

Ocular pigmentation in white and Siamese cats.

Ocular pigmentation in white cats with blue and yellow eyes and in Siamese cats was examined ophthalmoscopically and histologically. Yellow-eyed white cats had entirely normal ocular pigmentation. Blue eyes of white cats had normal pigmentation of the iridial and retinal pigment epithelia but no stromal pigmentation of the iris or choroid. This deficit is apparently due to the absence of stromal pigment cells, certainly in the iris. As a general rule, the blue eye of white cats had no tapetum. Siamese cats had reduced pigmentation of the iridial and retinal pigment epithelia and no stromal pigmentation of the iris or choroid. The lack of pigmentation is apparently due to the inability of stromal pigment cells to produce pigment, certainly in the iris. We conclude that the abnormality of visual pathways previously described in the Siamese cat is not due simply to a deficiency of pigment of cells of neural crest origin.

Animals

Lateral geniculate relay of slowly conducting retinal afferents to cat visual cortex.

1. Lateral geniculate neurones of the cat were studied in terms of the latency for activation by local electrical stimulation of the retina, the latency of electrical activation from the visual cortex and properties of receptive fields. Most of the units were relay cells (antidromic activation from visual cortex) but a small proportion were trans-synaptically activated from the cortex. The latter group included units with on-off, on-centre or off-centra receptive fields. 2. Direct activation of lateral geniculate neurones from local electrical stimulation of retinal ganglion cells or their axons in the retina was identified by the sharpness of timing of the elicited impulses. This procedure revealed the existence of slowly conducting axons relaying in the lateral geniculate nucleus. 3. The distribution of latencies for direct activation from the retina was bimodal with an extended tail of long values. It is similar to the distribution of antidromic latencies of retinal ganglion cells following stimulation of the optic tract. 4. There was a tendency for geniculate neurones with fast input from the retina to have fast axons to the visual cortex and correspondingly for medium-speed and slow input. 5. The previous classification of geniculate receptive fields into sustained and transient types was extended to include commonly encountered 'brisk' and uncommonly encountered 'sluggish' varieties of each. The extension was based on visual properties and latency for direct electrical activation from the retina. Units with receptive fields differing from the familiar on-centre or off-centre concentric pattern were encountered rarely; they included colour-coded fields, local-edge-detectors and one edge-inhibitory off-centre type.

Animals

Threshold setting by the surround of cat retinal ganglion cells.

1. The slope of curves relating the log increment threshold to log background luminance in cat retinal ganglion cells is affected by the area and duration of the test stimulus, as it is in human pyschophysical experiments. 2. Using large area, long duration stimuli the slopes average 0-82 and approach close to 1 (Weber's Law) in the steepest cases. Small stimuli gave an average of 0-53 for on-centre units using brief stimuli, and 0-56 for off-centre units, using long stimuli. Slopes under 0-5 (square root law) were not found over an extended range of luminances. 3. On individual units the slope was generally greater for larger and longer test stimulus, but no unit showed the full extent of change from slope of 0-5 to slope of 1. 4. The above differences hold for objective measures of quantum/spike ratio, as well as for thresholds either judged by ear or assessed by calculation. 5. The steeper slope of the curves for large area, long duration test stimuli compared with small, long duration stimuli, is associated with the increased effectiveness of antagonism from the surround at high backgrounds. This change may be less pronounced in off-centre units, one of which (probably transient Y-type) showed no difference of slope, and gave parallel area-threshold curves at widely separated background luminances, confirming the importance of differential surround effectiveness in changing the slope of the curves. 6. In on-centre units, the increased relative effectiveness of the surround is associated with the part of the raised background light that falls on the receptive field centre. 7. It is suggested that the variable surround functions as a zero-offset control that sets the threshold excitation required for generating impulses, and that this is separate from gain-setting adaptive mechanisms. This may be how ganglion cells maintain high incremental sensitivity in spite of a strong maintained excitatory drive that would otherwise cause compressive response non-linearities.

Action Potentials