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Biomedical subjects

T Pasternak

Publications and source records attributed to T Pasternak.

33 records · Page 2Linked to original sources

Selective damage to large cells in the cat retinogeniculate pathway by 2,5-hexanedione.

The neurotoxic hexacarbon 2,5-hexanedione (2,5-HD), which produces transport abnormalities and swellings in the large diameter fibers of the peripheral nervous system, was administered to cats in an attempt to produce similar selective effects in the optic tract. Anatomical findings indicate damage to one type of retinal ganglion cell, the large (alpha) or Y-cell class, both during dosing and after a long recovery period. This selective involvement of the large ganglion cells during dosing was shown by decreased retrograde transport of HRP in these cells relative to smaller cells. Such selectivity was not apparent in axonal swellings and neurofilament accumulations which were present in fibers of all diameters in the distal optic tract. Visual threshold studies during dosing showed a loss of flicker resolution with preservation of visual acuity, a result consistent with the different physiological properties of alpha and beta ganglion cells. In one cat, which survived dosing for a period of 8 months, there was a dramatic reduction in the number of large cells and a pronounced shrinkage of those that remained, but no observed changes in other cell types. Thus, this intoxication caused (1) axonal swellings which were not selective for fiber size; (2) a selective defect in axonal transport with later neuronal degeneration and shrinkage that were limited to large cells; and (3) a loss of flicker resolution that may reflect dysfunction of large ganglion cells.

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Effects of stimulus speed on direction discriminations.

Difference thresholds for the direction of movement of moving isotropic dot patterns were measured over a wide range of stimulus speeds. These measurements were made in human subjects, in normal cats and in visually deprived cats with abnormalities in neuronal directional response. For all subjects, direction thresholds were inversely related to stimulus speed at low drift rates. Above a "critical speed", direction thresholds were independent of stimulus speed. Between group differences in critical speed parallel differences in visual acuity and absolute thresholds for direction of motion. However, asymptotic direction thresholds appear to be unrelated to acuity and motion detection thresholds. It is argued that the basis for the differences in asymptotic direction thresholds between the groups are differences in properties of directional mechanisms.

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The role of area centralis in the spatial vision of the cat.

Spatial contrast sensitivity was measured over a 6 log unit luminance range in two cats before and after bilateral 4-5 deg radius argon laser lesions were placed in area centralis. The lesions reduced high luminance contrast sensitivity by approximately 0.3-0.4 log units at the low and middle spatial frequencies and by 0.5-1.0 log unit at the highest spatial frequencies. The loss of visual acuity was 0.4 octave in the cat with the smaller lesions and 0.8 octave in the cat whose lesions were larger. At lower luminance, little loss in contrast sensitivity was seen and no change was detectable at scotopic luminance levels. Visual acuity, on the other hand, was decreased at higher scotopic conditions, but unaffected at the lowest luminance levels tested (16 X 10(-6) cd/m2). These data indicate that area centralis plays an important role in detecting both high and low spatial frequencies under high luminance conditions but contributes only to spatial resolution at low luminance levels. This result is consistent with known anatomical and physiological properties of the cat area centralis.

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Motion mechanisms in strobe-reared cats: psychophysical and electrophysical measures.

Cats were reared from birth to at least 12 months of age in a visually static environment (illuminated 40/min by a 3 mu sec strobe flash). Single unit recordings from these animals revealed abnormalities in spatial and directional properties of cortical neurons. In an attempt to find psychophysical correlates of these neural deficits, spatial contrast sensitivity and motion detection thresholds were measured behaviorally. Both spatial vision and motion detection were greatly impaired. While spatial deficits failed to recover, motion thresholds improved greatly following extended training. These improvements in behavioral motion response were accompanied by the recovery of cortical directional selectivity. The recovery of motion thresholds and directional selectivity was direction specific: the distribution of the preferred directions of cortical neurons and motion thresholds were sharply biased towards the direction first seen in training. Thus, directional mechanisms of adult motion deprived cats may be modified if following deprivation the animals are trained to detect moving stimuli.

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Spatial and temporal vision of macaques after central retinal lesions.

Spatial contrast and temporal modulation sensitivity of two macaque monkeys were measured at three luminance levels before and after binocular laser coagulation of the fovea. The radius of the lesions ranged from 1.6 to 2.2 deg from the center of the fovea. After placement of the lesions, the visibility of high spatial frequencies was greatly reduced, although sensitivity at middle and low spatial frequencies was unaffected. No loss of spatial resolution was found at the lowest luminance tested. When temporal modulation sensitivity was tested with 4 deg targets, foveal lesions had no effect at any temporal frequency or luminance. However, with a 0.57 deg target, sensitivity to lower frequencies was impaired. Thus visual loss after destruction of the fovea is limited to high luminance, small targets, and the resolution of fine detail.

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Movement detection by cats: invariance with direction and target configuration.

Absolute thresholds for movement detection were measured in three cats and two human subjects under similar conditions. A two-alternative spatial forced-choice procedure was used with the method of constant stimuli. When targets were moving random-dot patterns, cat thresholds ranged from .6 degrees to 2.3 degrees/sec, while human thresholds were approximately .05 degrees/sec. Similar thresholds were found for cats tested with square wave gratings ranging in spatial frequency from .18 to 1 cycle/degree. Neither cats nor humans showed any directional asymmetry for motion detection.

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Intensity difference thresholds after lesions of the visual Wulst in pigeons.

Visual intensity difference thresholds were studied before and after telencephalic lesions in pigeons. Subjects with visual Wulst lesions showed initial postoperative threshold elevations that represented losses of 19%-49% of their preoperative sensory capacity. This initial loss was correlated with the extent of damage to three components of the visual Wulst: nucleus intercalatus hyperstriati accessorii, hyperstriatum intercalatus suprema, and hyperstriatum accessorium. The damage to hyperstriatum dorsale, another component of the visual Wulst, made no contribution to the initial deficit. The sensory capacity of all but one pigeon improved as a result of postoperative retraining.

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Delayed matching performance after visual Wulst lesions in pigeons.

Pigeons were trained preoperatively on a mixed delayed matching-to-sample (DMTS) task in which six different conditions were presented randomly; simultaneous matching, 0-, 1-, 2-, 4-, and 8-sec delays. Subjects that sustained extensive or complete damage to the visual Wulst and moderate damage to hyperstriatum ventrale showed a decrease in accuracy of performance to chance levels at all of the delay conditions as well as on simultaneous matching. After extensive retraining on the 0-sec-delay matching alone, performance on 0-sec-delay and simultaneous matching, presented in mixed DMTS, improved to between 70% and 90% correct. However, performance on delay conditions remained at chance level. All but one bird failed to show signs of postoperative improvement on delay problems in the course of the final testing. The data suggest that the conditional property of the task was a critical factor in the initial drop in accuracy on all of the presented problems. The relatively permanent loss of accuracy on all delay conditions is attributed mainly to the temporal separation of sample and comparison stimuli.

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Motion perception following lesions of the superior temporal sulcus in the monkey.

We examined the effect of bilateral ibotenic acid lesions, aimed at areas MT/MST in three macaques, on their perception of motion. The medial boundary of the lesions in the three monkeys was near the dorsal end of the STS, but the lesions extended different lengths ventrally along the STS. The lesions extended the shortest distance ventrally monkeys 1 and 2, covering most of MST but possibly sparing a portion of lateral MT. That in monkey 3 damaged all of MT and MST bilaterally and extended through most of FST. All three lesions caused a temporary disruption, followed by at least partial recovery, of most motion thresholds. Permanent effects of the lesions on visual sensitivity were graded with lesion extent. Contrast sensitivity for detecting low-spatial-frequency (1 cycle/degree) drifting gratings over a wide range of drift rates, as well as for identifying their direction of motion, was slightly affected only in monkey 3. Only monkeys 2 and 3 showed a deficit in discriminating stimulus speed, and the size of the loss was two- to fourfold. Discrimination of opposite directions of dot pattern motion, which required integration of local motion signals, was mildly affected in monkeys 2 and 3, and not affected in monkey 1. However, addition of directional noise to this discrimination caused the performance of all monkeys to be permanently disrupted, especially that of monkeys 2 and 3. Finally, direction difference thresholds were elevated by a factor of 2-4 after the lesions in all three monkeys. Many of these deficits were more pronounced during the first 2 months of testing following the lesion. Thus, our results demonstrate that areas within dorsal STS make an important contribution to the performance of various motion perception tasks including the discrimination of small differences in direction and speed, and the perception of global motion in the presence of directional noise. The residual motion perception, even in the monkey with virtually complete removal of areas MT/MST, may suggest either that these tasks are normally mediated in part by cortical areas outside of areas MT and MST, or that the disrupted functions were partially assumed by other cortical areas after lesions.

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Lesions in cat lateral suprasylvian cortex affect the perception of complex motion.

We examined the effects of bilateral ibotenic acid lesions of cat lateral suprasylvian (LS) cortex on motion perception. Cats were tested on tasks requiring integration of local directional signals, precise judgements of direction and extraction of structure-from-motion. All animals showed permanent deficits in integrating local motion signals. These deficits were most pronounced in the presence of directional noise and at larger spatial displacements. In addition, LS lesions produced a 2-fold loss in the accuracy of direction discrimination and large deficits in the perception of structure-from-motion. All of these losses were most severe during the first few weeks of testing following the lesion. These findings demonstrate that LS cortex plays an important role in the processing of stimuli requiring integration of motion information and limits the spatial scale over which such integration can proceed. Partial improvements in performance with time and/or training may be indicative of post-operative plastic changes in neurons outside of LS cortex.

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Transient and permanent deficits in motion perception after lesions of cortical areas MT and MST in the macaque monkey.

We examined the nature and the selectivity of the motion deficits produced by lesions of extrastriate areas MT and MST. Lesions were made by injecting ibotenic acid into the representation of the left visual field in two macaque monkeys. The monkeys discriminated two stimuli that differed either in stimulus direction or orientation. Direction and orientation discrimination were assessed by measuring thresholds with gratings and random-dots placed in the intact or lesioned visual fields. At the start of behavioral testing, we found pronounced, motion-specific deficits in thresholds for all types of moving stimuli, including pronounced elevations in contrast thresholds and in signal-to-noise thresholds measured with moving gratings, as well as deficits in direction range thresholds and motion coherence measured with random-dot stimuli. In addition, the accuracy of direction discrimination was reduced at smaller spatial displacements (i.e. step sizes), suggesting an increase in spatial scale of the residual directional mechanism. Subsequent improvements in thresholds were seen with all motion stimuli, as behavioral training progressed, and these improvements occurred only with extensive behavioral testing in the lesioned visual field. These improvements were particularly pronounced for stimuli not masked by noise. On the other hand, deficits in the ability to extract motion from noisy stimuli and in the accuracy of direction discrimination persisted despite extensive behavioral training. These results demonstrate the importance of areas MT and MST for the perception of motion direction, particularly in the presence of noise. In addition, they provide evidence for the importance of behavioral training for functional recovery after cortical lesions. The data also strongly support the idea of functional specialization of areas MT and MST for motion processing.

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[Site-specific expression of single-stranded antibody fragments in Nicotiana tabacum].

Antibody expression and immunomodulation are modern molecular techniques to produce pharmaceuticals and to interfere with cellular metabolism or pathogen infectivity in plants. Nonetheless, there is still no generally applicable strategy to express correctly folded active antibodies or antibody fragments in different cell compartments. To facilitate expression, single-chain antibody fragments (scFvs) were made of mouse monoclonal antibodies, J2 and P6 that specifically recognize double-stranded RNA (dsRNA). Stabilizing double-stranded replication intermediates could modulate the biological activity of dsRNAs in plants, especially to influence virus replication. Along with cytoplasmic expression, scFvs were anchored to the plasma membrane; targeted to the apoplast for secretion and made ER-resident. Expression levels were analysed and transgenic plants were evaluated for resistance or tolerance to potato virus Y infection. We have established strategies for expression of correctly assembled antibodies or antibody fragments in different plant cell compartments.

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