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R P Scobey

Publications and source records attributed to R P Scobey.

At least 19 recordsLinked to original sources

Properties of K+ conductances in cat retinal ganglion cells during the period of activity-mediated refinements in retinofugal pathways.

During ontogeny retinal ganglion cells manifest pronounced changes in excitable membrane properties. To further our understanding of the ionic conductances underlying such functional changes, the whole-cell voltage-clamp variation of the patch-clamp technique was used to record potassium currents in 220 ganglion cells dissociated from cat retinas ranging in age from embryonic day 31 to postnatal day 10. Potassium currents were isolated by blocking voltage-gated Na+ and Ca2+ currents with tetrodoxin (TTX) and CoCl2 respectively and were characterized by their pharmacology, kinetics and voltage-dependence of activation and inactivation. In all cases, a combination of three currents accounted for the total outward calcium-independent K+ current: (i) a steady linear conductance; (ii) a voltage-gated transient current, IA, and (iii) a voltage-gated sustained current, IK. Both voltage-gated currents were affected by the application of 4-aminopyridine and tetraethylammonia (TEA): IA showed a greater sensitivity to 4-aminopyridine, while IK was more sensitive to TEA. Both voltage-gated currents were present throughout the developmental period examined; however, the percentage of retinal ganglion cells (RGCs) expressing IA showed a marked decline from 82% at E31 to 45% at postnatal ages. During this developmental period there was an increase in the density of the two voltage-gated and the linear conductance. Additionally, with maturation, significantly slower inactivation kinetics were observed for IK. These findings, and our previous results dealing with maturational changes in the TTX-sensitive voltage-gated Na current, are related to the generation of excitability in developing retinal ganglion cells. Furthermore, the presence of cells with and without transient K+ conductance throughout development suggests that the different spiking patterns observed in RGC classes may be partially due to differences in their membrane properties.

Aging

Prenatal development of excitability in cat retinal ganglion cells: action potentials and sodium currents.

The development of precise retinofugal projections is dependent on activity-mediated events, but as yet nothing is known about the ontogeny of excitable membrane properties in retinal ganglion cells (RGCs). In order to begin to understand how functional maturity is attained in these neurons, whole-cell patch-clamp recordings were obtained from acutely dissociated RGCs of fetal and postnatal timed-pregnant cats. Current-clamp recordings revealed a pronounced developmental increase in the proportion of RGCs capable of generating action potentials. At embryonic day 30 (E30), 5 weeks before birth and during a time when RGCs are still being generated, electrical stimulation elicited spikes in only a third of the cells. None of these neurons were capable of multiple discharges in response to maintained depolarization. The proportion of spiking neurons increased during ontogeny, such that by E55 all RGCs could be induced to generate action potentials, with the majority manifesting repetitive spiking patterns. Application of tetrodotoxin abolished spike activity of all fetal RGCs, indicating that sodium-mediated action potentials are present very early in development. At the same time, voltage-clamp recordings revealed significant ontogenetic modifications in several key properties of the sodium currents (INa). These were (1) a twofold increase in Na current densities; (2) a shift in the voltage dependence of both activation and steady state inactivation: with maturity, sodium currents activate at more negative potentials, while steady state inactivation of INa occurs at less negative potentials; and (3) a decrease in decay time constants of the Na current, at membrane potentials negative to -15 mV. These developmental changes were largely restricted to the period of axon ingrowth (E30-E38), suggesting that maturation of INa is not the limiting factor for the onset of activity-dependent restructuring of retinofugal projections.

Action Potentials

A horizontal stripe of displacement sensitivity in the human visual field.

Displacement thresholds of peripheral sites in monocular human vision were obtained. The average of 12 directional thresholds at different visual field sites was used to define isometric lines of average displacement threshold about central vision. Isometric lines extended further into the temporal visual fields along the horizontal meridian than along other meridians. At any single site in the peripheral visual field the thresholds were not the same in all directions; they were larger toward and away from central vision. These two psychophysical findings vary in a qualitatively similar manner across the retinal field, as does the average size and the collected orientation bias of dendritic fields of retinal ganglion cells.

Fixation, Ocular

Orientation discrimination sensitivity of single units in cat primary visual cortex.

Responses of visual cortex (area 17) neurons to moving oriented stimuli were recorded from anesthetized cats. The variance of response (SD2) to repeated identical stimuli was directly proportional to response magnitude (R), (SD2 = C2R). The values of C were not found to differ significantly between different types of cortical cells. The relationship predicts that the coefficient of variation (SD/R) will be smallest near the peak of the tuning curve, indicating that the peak response is most reliable for detecting an orientation but not necessarily the most sensitive to a change in orientation. Tuning curves and response variability were then examined to determine the orientation at which the neuron was most sensitive to changes in stimulus orientation using signal detection theory. The discrimination index (d' = [R1-R2]/SD) for a 1 degree change in stimulus orientation was greatest along the flanks of the tuning curve. In order to generalize the experimental data, response distributions derived from a model of cells with parameters based on experimental data were examined to determine the minimal discriminable change in stimulus orientation. Changes of stimulus orientation between 0.6 and 5 deg of arc could be detected from single responses of a single cell by an optimal observer with 75% accuracy if the orientation change was centered at the most sensitive part of the tuning curve.

Action Potentials

Response covariance in cat visual cortex.

The activity of pairs of neurons in the visual cortex (area 17) of anaesthetized, paralysed cats was recorded using two independently manipulated micropipettes. The number of spikes in the evoked responses of pairs of single neurons were analyzed for response covariance. Responses of the majority of cell pairs (83%) did not covary. Covariance was restricted to closeby neurons with distances of less than 150 microns and with identical orientation and ocular dominance preference.

Analysis of Variance

Intracranial pressure during epileptic seizures.

A comatose 31-year-old male with presumed viral encephalitis and frequent partial motor seizures was paralyzed with pancuronium in an attempt to reduce recurrent elevation of intracranial pressure (ICP) associated with each seizure. ICP was continuously monitored with a Richmond Bolt and 5 electrographic seizures originating in the left frontal area were recorded. Each ictal episode was associated with stable blood pressure and an increase of ICP. The average seizure duration was 78 +/- 17 sec (mean +/- S.D.) and the average maximum increase of ICP above baseline during the seizures was 6.5 +/- 0.6 mm Hg with average peak ICP of 16.0 +/- 0.86 mm Hg. A simple mathematical model predicts the rate of increase of ICP, the peak ICP, the phase difference between maximum spike frequency and maximum ICP, and the rate at which ICP returns to pre-ictal values after termination of the seizure. The predicted values of ICP closely approximate the experimentally derived data. Therefore, the time course of the ICP appears to be determined by the frequency of the fundamental units of abnormal synchronized activity (the epileptogenic spike) and the CSF pressure-volume dynamics existing at the time of the seizure. An average increment of ICP per spike can be calculated for each seizure. The model also predicts that patients may develop high ICPs due to prolonged seizures. Prolonged unrecognized seizures may occur in patients who are therapeutically paralyzed as demonstrated by the case described here.

Adult

Effects of retinal eccentricity on displacement thresholds for unidirectional and oscillatory stimuli.

Motion sensitivity was determined for line stimuli undergoing unidirectional and oscillatory displacements at various retinal eccentricities. Oscillatory motions of short duration were found to produce consistently greater motion thresholds than unidirectional stimuli at each eccentricity tested. Increasing retinal eccentricity elevated motion thresholds similarly for both forms of stimulus motion. The observed differences between unidirectional and oscillatory stimuli are attributed to differences in the temporal summation of the two forms of stimuli at short duration. These findings also suggest that differences in motion sensitivity between central and peripheral vision are quantitative rather than qualitative.

Fovea Centralis

Effects of reference lines on displacement thresholds at various durations of movement.

Displacement thresholds were determined for durations of movement between 10 msec and 2.5 sec, with and without the presence of a reference line. For all durations of movement, displacement thresholds were lower when a reference line was present. The magnitude of this effect was essentially constant across all durations of movement. These data suggest that previous reports of differential effects of reference lines on long and short durations of movement depend upon the stimulus paradigm employed.

Humans

The luminance and response range of monkey retinal ganglion cells to white light.

The responses of single retinal ganglion cells of the monkey to spot stimuli were recorded with extracellular microelectrodes. The stimulus was centered on the receptive field, adjusted in diameter to optimally excite the cell and incremented and decremented from the background level. The response range was defined as the difference between the maximum and minimum response amplitude evoked with a wide range of luminances. The difference in luminance between the luminances which evoked the maximum and minimum responses was defined as the luminance range for dynamic response. The response amplitude range and luminance range to white light were negatively correlated to one another for the population of cells studied in central vision. The phasic cells had smaller luminance ranges for dynamic responses and a greater response magnitude for small changes in luminance from background than the tonic cells.

Action Potentials

Psychophysical properties of displacement thresholds for moving targets.

Psychophysical movement displacement thresholds were determined for three stimulus parameters (line length, stimulus luminance, and duration of movement) at various locations in the visual field. Although some differences were noted, foveal and peripheral movement displacement threshold functions were generally similar when scaled and plotted on logarithmic coordinates. The findings were consistent with known physiological and anatomical properties of retina, and suggest that retinal mechanisms are an important determinant of motion displacement threshold.

Differential Threshold