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Biomedical subjects

E L Smith

Publications and source records attributed to E L Smith.

At least 73 records · Page 4Linked to original sources
PubMed1995

Spectacle lenses alter eye growth and the refractive status of young monkeys.

The influence of visual experience on ocular development in higher primates is not well understood. To investigate the possible role of defocus in regulating ocular growth, spectacle lenses were used to optically simulate refractive anomalies in young monkeys (for example, myopia or nearsightedness). Both positive and negative lenses produced compensating ocular growth that reduced the lens-induced refractive errors and, at least for low lens powers, minimized any refractive-error differences between the two eyes. These results indicate that the developing primate visual system can detect the presence of refractive anomalies and alter each eye's growth to eliminate these refractive errors. Moreover, these results support the hypothesis that spectacle lenses can alter eye development in young children.

Accommodation, Ocular↗
PubMed1995

Transfer characteristics of lateral geniculate nucleus X neurons in the cat: effects of spatial frequency and contrast.

1. The dependence of signal transfer in the lateral geniculate nucleus (LGN) on stimulus spatial frequency and contrast was investigated by comparing responses of individual X cells with their direct retinal inputs. 2. We used extracellular single-cell recording methods to isolate action potentials (LGN) and S potentials (SPs) from individual neurons in layers A and A1 of anesthetized and paralyzed cats. The stimuli were drifting sinusoidal gratings that were presented at each neuron's preferred orientation. The effects of stimulus spatial frequency and contrast on retinogeniculate signal transfer were determined by comparing the amplitude of the fundamental Fourier responses measured for a cell's action potentials (LGN) and its retinal input (SP) and calculating the transfer ratio (LGN amplitude/SP amplitude) for each stimulus condition. 3. In all units, the LGN response amplitude was lower than that of its retinal input regardless of stimulus spatial frequency. The mean transfer ratio measured at the peak spatial frequency for individual units was 0.56 +/- 0.03 (SE). For the majority of X LGN neurons, however, the efficiency of signal transfer varied considerably with stimulus spatial frequency. The average transfer ratio increased monotonically from 0.08 cycle/deg to near the high cutoff spatial frequency. 4. The effects of stimulus contrast on geniculate signal transfer were far more complex than previously reported and varied substantially between individual neurons. At low stimulus contrasts (< 10%), where all units exhibited linear response characteristics, only one third of our sample showed a monotonic decrease in transfer ratio with increasing stimulus contrast. The remaining two thirds either exhibited proportionately greater signal transfer for higher stimulus contrasts, or signal transfer remained relatively unchanged with increasing stimulus contrasts. When stimulus contrasts exceeded 10%, where response amplitude began to saturate, the transfer ratio was relatively constant in all units and independent of stimulus contrast. 5. Our results demonstrate that signal transfer from retina to visual cortex is regulated by LGN neurons in a stimulus-dependent manner, which appears to reflect the complex interactions between local membrane mechanisms and extraretinal inputs.

Action Potentials↗
PubMed1995

Transfer characteristics of X LGN neurons in cats reared with early discordant binocular vision.

1. The effects of early discordant binocular vision on the functional development of the cat lateral geniculate nucleus (LGN) were investigated by quantitatively comparing responses of individual LGN neurons with their direct retinal inputs. 2. Unilateral convergent strabismus (esotropia) was surgically induced in 11 kittens at the age of 3 wk. After the animals had reached 9 mo of age, extracellular microelectrode recordings were made from individual X LGN units in lamina A and A1 of anesthetized and paralyzed cats. Responses were measured for drifting sinusoidal gratings. Within-unit comparisons of LGN action potentials (LGN output) and S potentials (retinal input) were performed to determine the nature of signal transfer in the units driven by the deviating (N = 42) or nondeviating eyes (N = 29) of strabismic cats. The results were compared with similar data (N = 29) obtained from nine normal control cats. 3. The spatial resolution of many individual LGN units in strabismic cats was abnormally reduced relative to their retinal inputs. These differences were more pronounced in units that received inputs from the nasal retina of the contralateral eye. The resolution loss was closely associated with a dramatic decrease in the strength of the receptive field center mechanism of LGN units relative to their retinal inputs. Moreover, the efficiency of signal transfer for high-spatial-frequency stimuli, determined by the transfer ratio (response amplitude of LGN action potentials/amplitude of S potentials), was significantly lower in strabismic cats compared with normal controls. 4. In strabismic cats, contrast thresholds for the action potentials of individual LGN units were significantly higher than those determined for the S potentials. In normal cats, the input-output differences in contrast threshold were negligible. The observed contrast sensitivity loss was more pronounced for high-spatial-frequency stimuli. 5. The speed of signal transfer was significantly decreased in the LGNs of strabismic animals. The visual response latencies of many, but not all, X LGN cells in the strabismic cats were abnormally long when compared with those in normal control units, whereas SP latencies were virtually the same for strabismic and normal cats. Abnormal latencies were prevalent in units that exhibited contrast threshold deficits, and were more severe among the units receiving input from the contralateral nasal retina. 6. The deficits in strabismic cats were found in the LGN units innervated by the deviating and nondeviating eyes. However, for the majority of response measures, the units innervated by the deviating eyes showed notably larger deficits. 7. We conclude that the fidelity of signal transfer from the retina to the LGN is significantly reduced in cats reared with discordant binocular visual experience. Thus the adverse effects of early strabismus are not confined, at least in cats, to the visual cortex.

Animals↗
PubMed1995

Receptive-field properties of deafferentated visual cortical neurons after topographic map reorganization in adult cats.

When neurons in primary visual cortex of adult cats and monkeys are deprived of their normal sources of activation by matching lesions in the two retinas, they are capable of acquiring new receptive fields based on inputs from regions of intact retina around the lesions. Although these "reactivated" neurons respond to visual stimuli, quantitative studies of their response characteristics have not been attempted. Thus, it is not known whether these neurons have normal or abnormal features that could contribute to or disrupt an analysis of a visual scene. In this study, we used extracellular single-unit recording methods to investigate their stimulus selectivity and responsiveness. Specifically, we measured the sensitivity of individual neurons to stimulus orientation, direction of drift, spatial frequency, and contrast. Over 98% of all units in the denervated zone of cortex acquired new receptive fields after 3 months of recovery. Newly activated units exhibited strikingly normal orientation tuning, direction selectivity, and spatial frequency tuning when high-contrast (< 40%) stimuli were used. However, contrast thresholds of most neurons were abnormally elevated, and the maximum response amplitude under optimal stimulus conditions was significantly reduced. The results suggest that the striate cortical neurons reactivated during topographic reorganization are capable of sending functionally meaningful signals to more central structures provided that the visual scene contains relatively high contrast images.

Animals↗
PubMed1994

Early discordant binocular vision disrupts signal transfer in the lateral geniculate nucleus.

The mammalian lateral geniculate nucleus (LGN) is known to regulate signal transfer from the retina to the brain neocortex in a highly complex manner. Besides inputs from the brainstem, extraretinal inputs via corticogeniculate projections and local inhibitory neurons modulate signal transfer in the LGN. However, very little is known about whether the postnatal development of LGN signal-transfer mechanisms is influenced by early discordant binocular vision. By intraunit comparisons of responses between individual X-LGN cells and their direct retinal inputs, the efficiency of signal transfer was found permanently reduced due to an early interocular misalignment (strabismus). The contrast sensitivity and spatial resolution of cat LGN cells were significantly lower relative to their retinal inputs, and there was substantial decrease in signal-transfer speed. The observed physiological deficits were associated with immature X-retinogeniculate axon arbors. Thus, contrary to previous ideas, conflicting binocular inputs can produce neural deficits in subcortical visual structures.

Action Potentials↗
PubMed1994

Transfer characteristics of lateral geniculate nucleus X-neurons in the cat: effects of temporal frequency.

The dependency of intrageniculate signal transfer on stimulus temporal frequency was investigated by comparing responses of individual X-relay cells with their direct retinal inputs in anesthetized and paralyzed cats. Temporal frequency response functions of lateral geniculate nucleus (LGN) X-cells were more narrowly tuned than those of their retinal inputs. The efficiency of signal transfer was consistently highest at or around the geniculate cells' optimal temporal frequency, and the degree of signal transfer, which was more closely related to the LGN cells' firing rate than to the firing rate of their retinal input, decreased for both lower and higher temporal frequencies. The high temporal frequency cut-offs were significantly lower in geniculate cell responses than those of their direct retinal inputs. This reduction in temporal resolution was exaggerated for relatively low stimulus spatial frequencies. The present results provide clear evidence for the notion that LGN cells function as nonlinear temporal filters and that this stimulus-dependent signal transmission appears to be regulated by complex local mechanisms.

Action Potentials↗
PubMed1994

Effects of optically induced blur on the refractive status of young monkeys.

In each of eight rhesus monkeys, one eye was defocused with a -9 D contact lens beginning before 1 month of age for periods of 2-3 months. At the end of the rearing period, interocular comparisons showed that one subject had developed a relative axial myopia (3.0 D), however, five monkeys had developed a relative axial hyperopia (2.0-3.5 D). After discontinuing the contact-lens rearing procedure, the induced refractive errors diminished over time in all subjects. These results indicate that the defocus threshold for form-deprivation myopia is relatively high and that substantial levels of optical defocus which do not exceed this threshold typically produce axial hyperopia. The recovery data suggests that monkeys have an emmetropization mechanism which is sensitive to optical defocus, but the failure of this mechanism to compensate for the refractive errors simulated during the lens-rearing procedures suggests that this mechanism has a limited operating range.

Animals↗
PubMed1994

Interocular suppression produced by rivalry stimuli: a comparison of normal and abnormal binocular vision.

This study compares interocular suppression in subjects with early strabismus and/or anisometropia with binocular rivalry suppression in subjects with normal binocular vision. A psychophysical test-probe paradigm was used to measure the changes in luminance-increment detection thresholds associated with periods of phenomenal suppression. In subjects with normal binocular vision, rivalry suppression induced by viewing orthogonally oriented grating pairs produced a distinctive wavelength-dependent change in visual sensitivity; specifically, there was a greater reduction in sensitivity for short (e.g., 450 nm) vs. middle or long wavelength stimuli (e.g., 560 nm). In contrast, subjects with abnormal binocular vision, regardless of the type of early abnormal visual experience, showed more reduction in sensitivity for a 560-nm stimulus than for the short-wavelength, 450-nm stimulus. Moreover, the pattern of sensitivity change in subjects with abnormal binocular vision was the same for suppression induced by either rivalry stimuli or stimuli that would normally promote fusion. The results clearly indicate that interocular suppression in subjects with abnormal binocular vision is qualitatively different from normal binocular rivalry. Evidently, the processes that mediate binocular rivalry are very susceptible to environmental influences during early vision development and can be disrupted easily.

Adolescent↗
PubMed1994

Binocular interactions in striate cortical neurons of cats reared with discordant visual inputs.

The postnatal development of cortical binocularity is known to be adversely affected by early abnormal visual experience. However, little information exists on how the signals from the two eyes are combined in individual cortical neurons of animals reared with early discordant binocular visual experience. Since this is a fundamental issue in understanding visual cortical development, we used extracellular single-unit recording methods to study binocular integration in striate cortical neurons of strabismic cats. Specifically, we measured the sensitivity of individual cells to the relative interocular spatial phase of dichoptically presented drifting sinusoidal gratings (i.e., to binocular retinal image disparity). Clear alterations in ocular dominance were observed in all strabismic subjects. Nevertheless, the majority of cortical neurons exhibited some form of binocular interactions when both eyes were stimulated together. The most prominent aspect of cortical physiology in the strabismic animals was the relatively high prevalence of suppressive binocular interactions. Suppression was most frequently found in kittens reared with 2 weeks of early optical dissociation and among adult cats that received 2 weeks of early optical dissociation and a prolonged recovery period. However, substantial excitatory binocular interactions were also maintained in these animals. With an extended period of interocular misalignment (3 or 8 months), all forms of binocular interactions, excitatory and suppressive, were drastically reduced and a greater number of neurons were truly monocular. Although the reduction in the strength of binocular interactions occurred in all units irrespective of their monocular spatial properties, the effect was more pronounced among those units tuned to higher spatial frequencies and this spatial-frequency-dependent effect was larger in the subjects receiving longer periods of binocular dissociation. The results suggest that the "breakdown" of cortical binocular properties in strabismic subjects is not an all-or-none process, and that suppressive binocular interactions may be closely associated with the abnormal binocular interactions exhibited by strabismic humans. Furthermore, our findings are consistent with the notion that cortical disparity-detecting mechanisms are spatial-frequency dependent and, thus, can be selectively altered depending on an animal's early visual experience.

Animals↗
PubMed1993

Does weight-bearing exercise affect non-weight-bearing bone?

It was previously reported that weight-bearing exercise increases femur periosteal formation in 3-year-old, 230 kg cross-bred sows. To determine if this weight-bearing exercise also stimulated non-weight-bearing bone, bone formation in the seventh rib from these same sows was measured histomorphometrically on the periosteal, endocortical, and osteonal envelopes. The sows were randomly assigned by body weight to basal (B, n = 6), control (C, n = 7), or trained (T, n = 7) groups. After 3 weeks of exercise adaptation, T walked on a treadmill for 17 weeks at 5 km/h, 20 minutes/day, 5 days/week, at 5% grade. Groups were sacrificed initially (B) or after 20 weeks (C and T). Periosteal mineral apposition rate (MAR) was calculated over 136 days. Osteonal and endocortical MAR were calculated over the 14 days prior to sacrifice. There were no effects of exercise on the periosteal or endocortical percentage double-labeled surface (dLS/BS), osteonal remodeling frequency (N.dL.On/B.Ar), or MAR in any bone envelope of the rib. In conclusion, weight-bearing exercise sufficient to stimulate periosteal formation in the femur did not activate formation in the rib. Bone response to weight-bearing exercise appears to be specific to the loaded bones.

Animals↗
PubMed1993

Synergistic induction of cytochrome P450 by ethanol and isopentanol in cultures of chick embryo and rat hepatocytes.

The purpose of this study was to investigate whether isopentanol, the most abundant higher chain alcohol in alcoholic beverages, contributes to induction of different forms of hepatic P450s associated with consumption of these beverages. We have previously reported that ethanol and isopentanol each induce P450 2H1/2 in cultured chick hepatocytes and that ethanol induced P450 2B1/2, as well as P450 2E, in cultured rat hepatocytes. Here we investigated the induction of P450 by isopentanol alone and in combination with ethanol in cultured chick and rat hepatocytes. The forms of induced P450 were identified both enzymatically and immunochemically. In cultured chick hepatocytes, both isopentanol and ethanol induced P450 2E, but combined treatment with these alcohols had no greater effect than treatment with ethanol alone. In cultured rat hepatocytes, isopentanol alone did not induce P450 2E or 2B1/2 and had no effect on the ethanol-mediated induction of P450 2E. However, isopentanol combined with ethanol caused a synergistic induction of P450 2B1/2 in cultured rat hepatocytes and an additive to synergistic induction of P450 2H1/2 in cultured chick hepatocytes. The levels of enzyme activities induced by the combined alcohol treatment approached those induced by potent barbiturates. The results suggest that the pentanols in alcoholic beverages may be responsible for a barbiturate-like induction of P450 in hepatocytes.

Animals↗
PubMed1993

Keeping an eye on the brain: the role of visual experience in monkeys and children.

The quality of visual experience during infancy determines the functional sensitivity and precision of the mature primate visual system. Infant monkeys subjected to monocular form deprivation show a period of critical visual development that, though decreasing in sensitivity, lasts throughout the first 2 years of life. Photopic threshold spectral sensitivity appears to have a briefer critical period, which is essentially complete by 6 months old, whereas scotopic visual functions appear well developed by 3 months old. Binocular visual functions seem to have the longest period of sensitivity to abnormal visual experience because periods of monocular form deprivation initiated during the first 2 years affect visual functions. Viewing the world through prisms, which mimics the condition of strabismus, causes a permanent loss of cortical binocular cells and stereopsis in monkeys. This result explains stereoblindness in children having equivalent clinical histories.

Animals↗
PubMed1993

Colour vision anomalies following experimental glaucoma in monkeys.

Spectral sensitivity defects, associated with chronic elevated intraocular pressure (IOP) produced by Argon laser trabeculoplasty, were studied in monkeys. Increment-threshold spectral sensitivity (ITSS) and threshold versus intensity (TVI) functions were measured using a behavioural model. Elevated IOP resulted in short wavelength (SW) sensitivity losses characteristic of many ocular diseases. The amount of SW sensitivity loss for ITSS functions depended upon the intensity level and chromatic composition of the background field. The optimum condition identifying the greatest SW sensitivity reduction was a yellow background of moderate intensity (100-1000 Td). In the early stages of experimental glaucoma, the cone mechanisms and the rod mechanism typically showed decreased test and field sensitivities. The SW cone pathway has slightly greater threshold elevation (approximately 0.3 log unit) compared to the rod and cone pathways. On the other hand, in the advanced stages of experimental glaucoma, the largest sensitivity losses were in the longer-wavelength, red-green opponent mechanisms, with the rod and SW cone pathways showing smaller losses. The similarities of the colour vision anomalies in this animal model with those of patients with glaucoma, provides support for its use as an experimental model for human glaucoma.

Animals↗
PubMed1993

Mechanisms mediating visual detection in static perimetry.

PURPOSE: The usual stimuli in static perimetry are white-light luminance increments. However, the specific visual detection mechanisms involved in perimetry are unknown because all classes of neural mechanisms are sensitive to spectrally broadband stimuli. The objective of this study was to determine the relative sensitivities of nonopponent and opponent detecting mechanisms under standard perimetry test conditions. METHODS: Using trained rhesus monkey subjects, the relative sensitivities of the vision mechanisms for the detection of perimetry test stimuli were determined through psychophysical measurements of spectral sensitivity at each of the test field locations of the C24-2 threshold program on the Humphrey Field Analyzer (Allergan Humphrey, San Leandro, CA). The spectral sensitivity functions were analyzed by a three-channel model that incorporated independent short-wavelength-sensitive, nonopponent (luminance), and opponent (chromatic) spectral sensitivity mechanisms. RESULTS: The visual detection mechanisms for perimetry thresholds varied as a function of the size and wavelength of the test field. With the perimeter's standard stimulus (Goldmann Size III) and bowl illumination (31.5 asb), the presence of a short-wavelength-sensitive mechanism was clearly evident at all field locations, but its relative sensitivity systematically declined with eccentricity. Under these conditions, the sensitivities of the opponent and nonopponent mechanisms were approximately equal at most field locations. With a larger stimulus (Goldmann Size V), however, the contribution of the opponent spectral sensitivity mechanism was more apparent over most of the central field and the alterations of sensitivity with eccentricity were less pronounced. In contrast, a small test field (Goldmann Size II) appeared to bias detection toward nonopponent mechanisms. CONCLUSION: The results of these investigations indicate that detection thresholds during perimetry can be effectively biased toward different photopic, visual processing channels through the appropriate selection of size and wavelength of the test stimulus.

Animals↗
PubMed1993

Behavioral perimetry in monkeys.

PURPOSE: Normative data on the systematic changes in visual sensitivity as a function of retinal eccentricity have provided the basis for efficient threshold strategies and data analysis routines for static perimetry. The standard methods of assessing visual field changes in patients also could be used for monkeys with experimentally induced ocular disorders if the normal visual fields of monkeys and humans were similar. METHODS: Normal visual field data from three rhesus monkeys were compared to data from eight human subjects using the standard threshold programs of the Humphrey Field Analyzer. RESULTS: The experimental paradigm developed for these measurements provided excellent behavioral control for the monkeys, with reliability indices well within acceptable limits. The visual field data from monkeys were comparable to those from humans with respect to: (1) sensitivity as a function of stimulus field size; (2) the derived Statpac global indices; and (3) the variance of threshold measurements across the visual field. CONCLUSION: The visual fields of monkeys and humans are similar, and the techniques of computerized perimetry may be applied to monkey subjects without significant modification.

Adult↗