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Biomedical subjects

W Burke

Publications and source records attributed to W Burke.

At least 127 records · Page 7Linked to original sources

Age of onset in Huntington's disease: lack of parental age effect.

In a recent publication Brackenridge and Teltscher (1975) concluded that the age of onset of Huntington's disease was in part a function of the age of the transmitting parent at the time of birth of a subsequently affected child. Their analysis suggested that the younger the parent was at the time of birth of the subsequently affected child, the later in life symptoms of disease would appear in the child. The data of Brackenridge and Teltscher have been statistically reevaluated here, and this analysis fails to support their conclusion. Consequently it would be irresponsible to counsel persons at risk for Huntington's disease to plan families early in life.

Age Factors↗

Temporal order in yeast chromosome replication.

Previous work with bacteria has shown that a gene is maximally sensitive to mutagenesis by N-methyl-N'-nitro-N-nitrosoguanidine (NG) at the time it is being replicated. NG was used to test for temporal order in the replication of the genome of the unicellular eucaryote, Saccaromyces cerevisiae. Yeast cells growing exponentially were more sensitive to mutagenesis by NG than cells in which DNA synthesis had been inhibited. Further, in a synchronized population of cells, individual genetic markers exhibited maximum sensitivity to muta-genesis at distinct limited intervals within the DNA synthesis period. The peaks of sensitivity are interpreted as reflecting the times of replication of different genes. Since markers for five genes on four different chromosomes showed discrete periods of maximum sensitivity, it is likely that temporal ordering of replication exists for most genes in the yeast genome. These results imply that sites for initiation of DNA replication occur at fairly specific regions along yeast chromosomal DNA moleucles, and are activated at predetermined times in the DNA synthesis period.

Cell Division↗

Disuse in the lateral geniculate nucleus of the cat.

1. An attempt has been made to produce disuse in the lateral geniculate nucleus (LGN) of the cat, in the synapses between the optic nerve fibres and the principal cells of the nucleus. Evidence is produced that destruction of the visual receptor cells by iodoacetate or 1,5-di(p-aminophenoxy) pentane dihydrochloride effectively silences the optic nerve discharge and so achieves this result.2. Disuse of the LGN synapses does not cause any decrease in synaptic efficiency. The LGN response to a single stimulus to the optic nerve was not appreciably altered, and the depression which normally follows single or repeated stimuli was much reduced or absent. This increased responsiveness was unaffected by prolonged tetanization of the optic nerve during the experiment.3. Two possible explanations of the increased responsiveness are suggested: a post-synaptic ;decentralization'-hypersensitivity and an increased output of transmitter per impulse. The relevance of these results to theories of learning is discussed.4. The LGN response of adult cats kept in complete darkness for periods of up to 966 days was not appreciably different from that in the normal cat and there was little or no increased responsiveness. This suggests that many retinal ganglion cells continue to discharge in total darkness for long periods. There is a possibility that disuse may develop after a long time in the dark.

Aniline Compounds↗

Discharge patterns of principal cells and interneurones in lateral geniculate nucleus of rat.

1. The cells of the lateral geniculate nucleus of the rat are classified into one of two distinct groups on the basis of their responses to a single shock to optic nerve or visual cortex. The distinctive difference between these two groups is that the P cells (87% of all cells) responded with short bursts of 1-5 spikes, whereas the I cells (13%) responded with long bursts of about 10 spikes. Both groups give recurring bursts at intervals of 100 msec or more for a total duration of up to about 5 sec.2. The majority of P cells (75%) have a lower threshold for late firing than for early firing. The majority of I cells (62%) have about the same threshold and all I cells have very low thresholds.3. To stimulation of the optic nerve the mean latency of the first spikes of all P cells is 4.4 msec. The mean latency of the first spikes of all I cells is 5.8 msec. The latency of the earliest spike in an I cell is 0.9 msec longer than the earliest spike in a P cell.4. To stimulation of the visual cortex the latency of the earliest spike in an I cell is 1.0 msec longer than the earliest spike in a P cell. Most P cells (78%) respond with either very short latency (less than 1.7 msec) or with a wave form characteristic of antidromic invasion or both. No I cell has either of these characterstics.5. It is concluded that P cells are principal cells projecting to visual cortex and that I cells are interneurones.

Animals↗

Recovery of responsiveness of cells of lateral geniculate nucleus of rat.

1. Recovery of responsiveness of single cells in lateral geniculate nucleus of rat has been determined in both P and I cells. There are three types of recovery curve among P cells; (a) early recovery, (b) early partial recovery followed by depression and then complete recovery, (c) prolonged depression followed by cyclic recovery. Type (c) is by far the commonest recovery curve. In contrast to the spike in a P cell, the synaptic potential recovers to its full amplitude in about 20 msec. All I cells exhibit similar rapid recovery curves after a prolonged depression.2. Conditioning stimuli applied to visual cortex also produce a prolonged depression in most P cells but I cells can be re-excited at short intervals from cortex. Decortication does not prevent the prolonged depression of the multineuronal response produced by optic nerve stimulation.3. A neuronal model is proposed to explain these observations. It is supposed that I cells (interneurones) are innervated by axon collaterals of the P cells (principal cells, projecting to visual cortex) and that the I cells exert an inhibitory influence on the P cells.

Animals↗

Inhibitory mechanisms in lateral geniculate nucleus of rat.

1. An examination was made of the mechanisms responsible for the inhibition of synaptic transmission through the lateral geniculate nucleus (LGN) of the rat following a single shock to the optic nerve.2. In the rat anaesthetized with paraldehyde we found no evidence that optic nerve stimulation produced any presynaptic inhibition in LGN. In agreement with other workers it was found that repetitive stimulation of visual cortex produced effects attributable to presynaptic inhibition. However, this was of small magnitude in the conditions of our experiments.3. Stimulation of the optic nerve elicited an action potential in a P cell (principal cell) which was followed by a wave of hyperpolarization lasting about 150 msec (inhibitory post-synaptic potential, IPSP, wave).4. The IPSP wave was chloride-dependent and was associated with inhibition of the P cell discharge. Occasional rippling on the IPSP wave suggests that it was produced by the repetitive discharge of I cells (interneurones).5. These observations support the model proposed previously wherein P cells are inhibited by I cells which in turn are excited by axon collaterals of P cells. There is evidence for diffuse interconnexions between P cells and I cells.6. The observation that the extracellularly recorded wave of hyperpolarization (P-wave) is usually negative suggests that most of the inhibitory synapses are not on the soma of the P cell.

Action Potentials↗

Processing of form and motion in area 21a of cat visual cortex.

Extracellular recordings from single neurons have been made from presumed area 21a of the cerebral cortex of the cat, anesthetized with N2O/O2/sodium pentobarbitone mixture. Area 21a contains mainly a representation of a central horizontal strip of contralateral visual field about 5 deg above and below the horizontal meridian. Excitatory discharge fields of area 21a neurons were substantially (or slightly but significantly) larger than those of neurons at corresponding eccentricities in areas 17, 19, or 18, respectively. About 95% of area 21a neurons could be activated through either eye and the input from the ipsilateral eye was commonly dominant. Over 90% and less than 10% of neurons had, respectively, C-type and S-type receptive-field organization. Virtually all neurons were orientation-selective and the mean width at half-height of the orientation tuning curves at 52.9 deg was not significantly different from that of neurons in areas 17 and 18. About 30% of area 21a neurons had preferred orientations within 15 deg of the vertical. The mean direction-selectivity index (32.8%) of area 21a neurons was substantially lower than the indices for neurons in areas 17 or 18. Only a few neurons exhibited moderately strong end-zone inhibition. Area 21a neurons responded poorly to fast-moving stimuli and the mean preferred velocity at about 12.5 deg/s was not significantly different from that for area 17 neurons. Selective pressure block of Y fibers in contralateral optic nerve resulted in a small but significant reduction in the preferred velocities of neurons activated via the Y-blocked eye. By contrast, removal of the Y input did not produce significant changes in the spatial organization of receptive fields (S or C type), the size of the discharge fields, the width of orientation tuning curves, or direction-selectivity indices. Our results are consistent with the idea that area 21a receives its principal excitatory input from area 17 and is involved mainly in form rather than motion analysis.

Animals↗

Effects of eliminating retinal Y cell input on center-surround interactions in the dorsal lateral geniculate nucleus of the cat.

The aim of this project was to investigate the interaction between Y retinal ganglion cells and the cells of the dorsal lateral geniculate nucleus (LGNd) of the cat, with particular reference to center-surround antagonism and intrageniculate inhibition. Responses of cells in the LGNd were studied by stimulating the retina with spots of light of constant contrast but varying size. The peak discharges of nonlagged X (XN) cells were strongly suppressed with increase in spot size but the responses of lagged X (XL) cells and nonlagged Y (YN) cells were inhibited much less strongly. The effect of the Y system on these responses was examined by producing a selective block of conduction in Y fibers in one optic nerve by means of a pressure cuff (Y-blocking). These effects were assessed by measuring the peak discharge rates and by calculation of a "peak suppression index." Y-blocking had no significant effect on the peak suppression index of XL cells in either lamina or on YN cells in the normal (not Y-blocked) lamina but had significant effects on the responses of XN cells, causing a decrease in peak suppression index, both for cells in laminae receiving their principal excitatory input from the Y-blocked eye (both lamina A and lamina A1) as well as those in lamina A (but not lamina A1) receiving their excitatory input from the normal eye. These effects were obtained with relatively large spots of light. Thus Y optic fibers have both intralaminar (monocular) and interlaminar (binocular) inhibitory effects on XN cells. In addition to these suppressive effects, the experiments also show that ipsilaterally projecting Y fibers have facilitatory effects on XN cells in lamina A when small spots of light, about optimal size for the XN cell, are used. These results suggest that the Y system plays a powerful role in shaping the responses of XN cells, possibly enhancing visual acuity.

Animals↗

Areas PMLS and 21a of cat visual cortex: two functionally distinct areas.

We have compared the receptive field properties of neurons recorded from visuotopically corresponding regions of area 21a and the posteromedial lateral suprasylvian area (PMLS) of cat visual cortex. In both areas, the great majority of neurons were orientation-selective and binocular, and their responses to moving contours were modulated by simultaneous in-phase or anti-phase motion of large textured background stimuli ('visual noise'). However, despite the great hodological similarity between the two areas, PMLS neurons had on average significantly higher peak discharge rates, exhibited substantially greater direction selectivity indices, and preferred substantially higher stimulus velocities than area 21a neurons. Furthermore, the majority of binocular neurons in the PMLS area and in area 21a were dominated respectively by contralateral and ipsilateral eyes. Finally, while 46% of PMLS neurons were excited by movement of visual noise per se, only 25% of area 21a neurons could be excited by such stimuli. We argue that the PMLS area, like its presumed primate homologue the middle-temporal (MT) area, is mainly involved in motion analysis. By contrast, area 21a appears to be involved in pattern analysis rather than motion analysis. It is likely that phylogenetically area 21a derives from the PMLS area.

Animals↗