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T T Norton

Publications and source records attributed to T T Norton.

At least 37 records · Page 2Linked to original sources

Experimental myopia in tree shrews.

When deprived of form vision during postnatal development, tree shrews reliably develop an axial myopia characterized by elongation of the vitreous chamber, zonular dysplasia and a slight reduction in lens weight and thickness. Corneal flattening has been observed in animals visually deprived by eyelid suture but is absent in animals visually deprived with an opaque goggle. The sensitive period for myopia development starts about 15 days after the eyes open and sensitivity remains high for about 3-4 weeks thereafter. Recovery from experimental myopia can occur in tree shrews that are visually deprived using goggles for a short period. Blockade of action potentials from ganglion cells in deprived eyes by intravitreal injections of tetrodotoxin (TTX) does not prevent the development of myopia, suggesting that local retinoscleral mechanisms can contribute to experimental myopia in this species. Open eyes receiving intravitreal injections of either saline or TTX have shorter vitreous chambers than control eyes, suggesting that puncturing the globe reduces forces within the eye that contribute to its expansion. Animals treated intraperitoneally with lathyritic agents to block collagen cross-linking for three weeks during a 75-day period of monocular visual deprivation develop a very large myopia in the visually deprived eye that is accompanied by a large vitreous chamber elongation and marked thinning of the posterior sclera. The results from studies in tree shrews are consistent with the suggestion that an internally driven expansion acts in concert with ocular growth to increase the axial length of the eye, helping to move the eye from hyperopia toward emmetropia. The resistance of the sclera and/or choroid to this expansion may be affected by activity within the retina. Increased retinal activity associated with achieving a clear image on the retina may result in increased resistance to expansion, helping to hold the retina at the focal plane. Recovery may occur by a slowing of axial expansion while the optical surfaces proceed toward adult values.

Aminopropionitrile↗

Effects of bicuculline on signal detectability in lateral geniculate nucleus relay cells.

The lateral geniculate nucleus conveys the center-surround organized retinal receptive fields to the cortex in a way that does not significantly alter their spatial structure. However, non-retinal influences may change the 'strength' (detectability) of the signal under conditions of anesthesia, arousal and attention. A previous analysis of receiver operating characteristic curves in cat suggests that a reduction in signal detectability occurs in lateral geniculate nucleus (LGN) relay cells in anesthetized animals in comparison to the retinal afferents. In the present study, it was found that antagonism of GABAA receptors with bicuculline (BIC) increased signal detectability in LGN relay cells in the tree shrew (Tupaia belangeri). This change is consistent with the hypothesis that feedforward and/or feedback GABAergic circuits in the LGN differentially affect the retinogeniculate transfer ratio for visually driven activity versus maintained (spontaneous) activity. Under conditions of arousal or attention, signal detectability may be increased by brainstem activation, thus increasing the flow of information in the visual system.

Action Potentials↗

Effects of bicuculline on receptive field center sensitivity of relay cells in the lateral geniculate nucleus.

The lateral geniculate nucleus (LGN) receives input from the retina that is spatially organized into a receptive-field center and surround. It maintains this organization in the signal that it sends to the visual cortex. Previous studies have focused on changes in the receptive-field 'surround' that are generated at the LGN, possibly as a local contrast enhancement mechanism. The present study suggests a role for the LGN in regulating the receptive-field center sensitivity under the control of GABAergic circuitry. Local microiontophoresis of the GABAA receptor antagonist bicuculline increased the contrast sensitivity of LGN relay cells to many spatial frequencies. Difference of Gaussians analysis showed that the increased was due to an increased sensitivity of the receptive-field center. Similar increases in receptive-field center sensitivity may be produced during behavioral arousal by the action of pontine and mesencephalic pathways upon the activity of the LGN GABAergic circuitry.

Action Potentials↗

Refractive and structural measures of lid-suture myopia in tree shrew.

In order to study more thoroughly the refractive and structural changes associated with lid-suture myopia, five tree shrews were raised for approximately 16 weeks with monocular visual experience produced by lid closure. Four animals raised with normal laboratory visual experience served as a control group. Compared to the paired open eye, lid-sutured eyes were myopic (-12.1 +/- 6.3 diopters by retinoscopy), corneas were flatter (0.26 +/- 0.18 mm radius increase by photokeratometry) and axial lengths were greater (0.32 +/- 0.17 mm longer by A-scan ultrasonography). The axial length increase was due to elongation of the vitreous chamber (0.38 +/- 0.19 mm longer by A-scan ultrasonography). The open eyes of experimental animals were not significantly different than the normal eyes of control animals. Two of these treatment effects, namely, refractive state changes and axial length increases, were demonstrated with independent techniques: streak retinoscopy was compared to coincidence optometry, and A-scan ultrasound was compared to axial measurements of photographs of frozen, sectioned eyes. The three main ocular effects of eyelid closure were stable over three measurement sessions completed within a 4 week period. Additional refractive and A-scan measurements taken 7.5 months later showed no significant changes. Optical modelling showed that the observed myopia of the lid-sutured eye is consistent with the observed elongation of the vitreous chamber coupled with the flattened cornea although other changes could not be ruled out. We conclude that an axial myopia is produced reliably in tree shrews by raising them with eyelid closure and that the measurement techniques used in this study have sufficient resolution to study the development of myopia in this species.

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Histochemical localization of cytochrome oxidase activity in the visual system of the tree shrew:normal patterns and the effect of retinal impulse blockage.

The tree shrew Tupaia belangeri has three functional pathways (ON-center, OFF-center, and W-like cells) that arise in the retina and proceed through separate LGN laminae to separate cortical targets. To determine whether these pathways have consistent differences in activity, cytochrome oxidase (C.O.) patterns were examined in the retina, LGN, and striate cortex. In six normal tree shrews the outer and inner plexiform layers of the retina were highly reactive for C.O. A pale, vascularized cleft zone separated the a (OFF) and b (ON) inner plexiform sublaminae, which seemed about equally reactive for C.O. In the LGN, laminae 1 and 2 (ON-center cells) and laminae 4 and 5 (mostly OFF-center cells) were highly reactive for C.O. LGN lamina 3 and 6 are part of an W-like afferent pathway. Lamina 3 was distinctly paler than laminae 1, 2, 4, and 5 while lamina 6 was intermediate. In the striate cortex, layer IV was the most reactive layer. Sublayer IVb (predominantly an OFF region) was consistently more reactive than sublayer IVa (predominantly ON). The middle portion, layer IVm, was paler than either IVa or IVb. This paler region includes, but extends above and below, the cell-sparse "cleft" region. Thus, considering all three levels of the retinogeniculostriate pathway, the ON and OFF systems were equally active until they reached the striate cortex, where the OFF system appeared to be more active than the ON. The W-cell laminae in the LGN exhibited the lowest level of activity. The contribution of ganglion cell activity to these patterns was assessed by intravitreal administration of tetrodotoxin (TTX) blockade either monocularly (three animals) or binocularly (two animals). In the TTX-treated retinae, the inner plexiform a and b sublaminae were paler for C.O., although visible, and were still separated by the pale cleft. The ganglion cell layer was very pale in comparison to the normal. In the LGN, monocular TTX blockade reduced the C.O. reactivity in the ON and OFF laminae that received input from the treated eye but had little effect on the W-like cell laminae. The ipsilaterally innervated ON and OFF laminae were more affected than were the contralaterally innervated laminae. Binocular TTX treatment resulted in a decrease of C.O. activity in the binocular segment of the ON and OFF LGN laminae. In the striate cortex, the most marked changes following TTX treatment occurred in layer IV.(ABSTRACT TRUNCATED AT 400 WORDS)

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Signal-to-noise comparisons for X and Y cells in the retina and lateral geniculate nucleus of the cat.

The spike trains of X and Y retinal ganglion cell axons and neurons in the lateral geniculate nucleus (LGN) of cats were compared to determine if the visual signal could be better discriminated from the maintained activity in the LGN relative to the retina. Curves for relative or receiver operating characteristics (ROC) were derived from the interspike interval data of the spike trains using maintained activity as "noise" and visually-driven activity as the "signal". Analyses were also made using spike densities and more restricted time intervals. Although it was expected that neurons in the LGN might better distinguish the signal from the noise, the results of the ROC curve and spike density analyses did not bear out this expectation; that is, neither the X or Y cells in the LGN provided better discrimination of the visually-driven activities from the maintained activities compared to the incoming retinal information. Thus, at least in the anesthetized preparation, the LGN does not play a role in increasing the signal-to-noise ratio.

Action Potentials↗

Laminar organization and ultrastructure of GABA-immunoreactive neurons and processes in the dorsal lateral geniculate nucleus of the tree shrew (Tupaia belangeri).

The distribution and ultrastructure of neurons and neuropil labeled by an antiserum to gamma-aminobutyric acid (GABA) were examined in the lateral geniculate nucleus (LGN) of the tree shrew (Tupaia belangeri). The LGN of this species segregates center type and cell class into three distinct pairs of laminae: a medial pair (laminae 1 and 2) containing ON-center cells, a more lateral pair (4, 5) containing OFF-center cells, and 2 laminae (3, 6) containing W-like cells. The relationship between this laminar segregation and the distribution of GABA immunoreactivity was investigated in the present study. GABA-immunoreactive neurons and neuropil were present in all six of the laminae. However, both the density of labeled cells (adjusted for neuronal density across laminae) and the density of labeled neuropil showed a medial-to-lateral gradient. The adjusted density of labeled cells was higher laterally than medially, and the density of labeled neuropil was significantly greater in the more lateral OFF-center laminae and W-like laminae than in the medial two ON-center laminae. Thus, inhibitory, GABAergic influences may modulate to different degrees the visual signals in the ON, OFF, and W pathways. Labeled cells had a mean cross-sectional area (107 microns 2) approximately one-half that of unlabeled cells (216 microns 2). They constitute 16-34% of the neurons in the LGN. At the electron microscope level, three different kinds of labeled profile were observed. Vesicle containing profiles like the F2 profiles of cat were postsynaptic to retinal terminals and presynaptic to conventional dendrites. F1 axon terminals with dense clusters of vesicles were also labeled as were some myelinated axons. Another labeled profile, which we suggest should be called an F3 process, was a large dendrite of irregular caliber with punctate groups of vesicles near the synapse. Our results suggest that GABAergic circuitry is an important part of the functional organization in the LGN of the tree shrew.

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Contrast-sensitivity functions of W-, X-, and Y-like relay cells in the lateral geniculate nucleus of bush baby, Galago crassicaudatus.

1. This paper represents a continuation of our effort to examine the relationship between the physiology of distinct classes of primate lateral geniculate nucleus (LGN) cells and spatial vision. The present study focuses on modeling the contrast-sensitivity functions (CSFs) of separate LGN cell classes, examining differences in the CSFs of different classes of LGN cells and comparing the results with behaviorally defined CSFs. 2. CSFs to drifting sinusoidal gratings were obtained from single LGN relay cells in the nocturnal primate, Galago crassicaudatus. The CSFs of 14 X-like, 27 Y-like, and 6 W-like cells with standard center-surround organization were well fit by a difference of Gaussians (DOG) model with small residual errors (mean error per data point +/- SEM = 0.008 +/- 0.002). The larger residual errors shown by a few of the Y-like cells were not due to nonlinearity of spatial summation. 3. The CSFs of eight cells that appeared to have nonstandard center-surround organization (primarily, a silent, suppressive surround) were also well fit by the DOG model. 4. The DOG curves that best fitted the data differed considerably between the three groups. As a group, X-like cells had a small center mechanism (Rc = 0.19 degrees) with high sensitivity (Kc = 76.53) and a small, sensitive surround (Rs = 0.71 degrees; Ks = 5.50). These parameters produced CSFs with high cutoff frequencies (Vcutoff = 2.5 c/deg) and low peak sensitivities (CSpk = 6.1) that occurred at 0.8 c/deg. 5. Y-like cells had a large center mechanism (Rc = 0.46 degrees) with low sensitivity (Kc = 21.16) and a large, insensitive surround (Rs = 2.38 degrees; Ks = 0.81). These parameters produced CSFs with lower cutoff frequencies (Vcutoff = 1.2 c/deg) and higher peak sensitivities (CSpk = 12.5) that occurred at 0.2 c/deg. 6. The few W-like cells that responded to gratings well enough to determine a CSF were quite variable. As a group they had a large center mechanism (Rc = 0.38 degrees) with intermediate sensitivity (Kc = 34.55) and a surround with intermediate size and sensitivity (Rs = 1.59 degrees; Ks = 1.59). These produced CSFs with intermediate cutoffs (Vcutoff = 1.6 c/deg) and low peak sensitivities (CSpk = 5.0) occurring at 0.4 c/deg.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Visual resolution and sensitivity in a nocturnal primate (galago) measured with visual evoked potentials.

Visual resolution and contrast sensitivity were examined in anesthetized, paralyzed galagos using visual evoked potentials (VEPs) resulting from stimulation with phase-reversed sinewave gratings. Spatial frequency vs contrast response functions were band-pass with peak sensitivity at 0.2-0.4 c/deg and a high frequency cut-off between 1.6 and 3 c/deg. Peak contrast sensitivities (estimated from extrapolation of contrast response functions) varied across animals from 10 to 170. Variation of the stimulus modulation rate showed that best responses occurred at 1 Hz with an upper limit of 6-16 Hz. As in other primates, an oblique effect was seen in 6 of 8 animals. The contrast sensitivity function (CSF) determined from cortical VEPs agrees well with the CSFs of cells in the lateral geniculate nucleus, but peak sensitivity and spatial frequency are slightly lower than found for the behavioral CSF. Overall visual performance resembled closely that of another nocturnal species, the cat.

Animals↗

Laminar organization of ON and OFF regions and ocular dominance in the striate cortex of the tree shrew (Tupaia belangeri).

The organization of ON and OFF responses and ocular dominance in the striate cortex of the tree shrew was electrophysiologically investigated by using flashed, stationary visual stimuli presented monocularly to either the ipsilateral or contralateral eye. We measured cortical multi-unit activity at 25-micron intervals with glass-insulated platinum-plated tungsten microelectrodes. Penetrations were made perpendicular to the cortical layers and the responses were quantitatively analyzed in layers IIIc to V. In sublayers IIIb, IIIc, and upper V, phasic responses of approximately equal magnitude occurred to both light ON and light OFF (ON-OFF regions). In layer IV, tonic as well as phasic responses were often evoked by the flashed spot of light. In sublayer IVa stronger responses occurred to light ON than to light OFF (ON region) while in sublayer IVb stronger responses occurred to light OFF than to light ON (OFF region). In an ON region, the increased neural activity that occurred at light ON was often accompanied by a decrease in activity below baseline level at light OFF. A similar decrease often occurred in an OFF region at light ON. Recordings from the region of the cell-sparse cleft in layer IV were characterized by ON-OFF responses, signalling a transition zone between sublayers IVa and IVb. In addition, the responses to stimulation of the ipsilateral eye typically were very weak in the cleft region. In the other regions examined, the multi-unit activity generally was driven binocularly with slightly greater responses being elicited by the contralateral eye. We conclude that the ON-center and OFF-center afferent pathways that are organized at the retinal level remain generally segregated in the tree shrew through the first synapse in the striate cortex. In addition, our recordings confirm that a horizontal organization of ocular dominance occurs in layer IV of the striate cortex in tree shrews.

Animals↗

W-like response properties of interlaminar zone cells in the lateral geniculate nucleus of a primate (Galago crassicaudatus).

Recent anatomical studies have suggested that the cells located in the interlaminar zones (ILZs) of the primate dorsal lateral geniculate nucleus (LGN) relay visual information from the retina to the striate cortex in a manner similar to that of W-cells in the LGN of cat. In the present study, we examined this idea directly by recording the response properties of single cells localized to the ILZs in the prosimian primate, Galago crassicaudatus. The properties of the cells in the ILZs were found to be physiologically distinct from the X-like and Y-like properties of the parvocellular and magnocellular LGN layers. Moreover, the small cells located in the interlaminar zones were physiologically similar to the W-like cells found in the specialized small-celled koniocellular layers in these primates. As is the case with the koniocellular layer cells, the ILZ cells exhibited a broad range of properties which, as a group, were distinguished by the following characteristics: the ILZ cells had long latencies to stimulation of the optic chiasm (mean, 3.95 ms) and to antidromic stimulation from striate cortex (mean, 3.31 ms) and had relatively large receptive-field centers (mean, 1.79 degrees). They also had low maintained discharge rates (5.5 spikes/s), relatively long response latencies to light (mean onset, 82 ms; peak, 112 ms) and low peak firing rates (59 spikes/s). Few (25%) had standard receptive-field organization (ON-center, OFF-surround, or vice versa). Only 29% responded well to sine-wave gratings and all were influenced by non-visual (auditory and tactile) stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

ON and OFF regions in layer IV of striate cortex.

In vertical penetrations through the striate cortex in the tree shrew (Tupaia belangeri), we found regions where neural activity was evoked predominantly by light ON. These were followed by regions where responses were evoked predominantly by light OFF. Histological reconstructions indicated that the ON regions were correlated with layer IVa and the OFF regions were correlated with layer IVb. Local application of cobalt chloride produced a transient cessation of visually evoked activity, suggesting that the electrodes sampled cortical activity rather than lateral geniculate nucleus afferents. These data demonstrate that separate ON and OFF regions are present in the tree shrew striate cortex and suggest that spatially separate, parallel ON and OFF afferent channels extend, in this species, at least through the first synapse in the striate cortex.

Animals↗

Effects of monocular deprivation on the lateral geniculate nucleus in a primate.

In many mammalian species, rearing with one eyelid closed produces a loss of vision in the deprived eye and a change in cell size in the lateral geniculate nucleus (LGN). In cats, the reduction in the size of deprived LGN cells has been correlated with a loss of one functional class of cells, Y cells. In primates, such as galago, LGN cells also exhibit marked changes in size with deprivation. In the present study we recorded from single cells in the LGN of monocularly deprived galagos to determine if such changes in cell size would be accompanied by changes in physiological properties. The results revealed no alterations in the distribution or functional properties of any cell class. The differences in the effects of monocular deprivation on the function of LGN cells in cats and primates are most easily explained by a fundamental difference in visual system anatomy. In cats, different classes of retinal afferents (X vs. Y) are in a position to compete for postsynaptic LGN neurons: in primates, segregation of cell classes into different layers may preclude such developmental interactions.

Aging↗

Topographic organization of the orientation column system in the striate cortex of the tree shrew (Tupaia glis). I. Microelectrode recording.

Microelectrode recordings were made in the binocular portion of the tree shrew striate cortex to determine how orientation selective cells are distributed topographically in area 17 of this species. Seventy-five percent of the cells sampled were activated well by elongated visual stimuli and were quite selective for stimulus orientation. Ninety-five percent of the orientation-selective cells had orientation tuning ranges (Wilson and Sherman, '76) between +/- 5 degrees and +/- 40 degrees from their optimal orientation. Orientation-selective cells with the same or similar optimal orientations were distributed in cortex in a columnar manner (Hubel and Wiesel, '62), as determined from electrode penetrations nearly normal to the cortical surface. Penetrations parallel to the cortical surface revealed a highly ordered representation of optimal stimulus orientation, generally characterized by sequential changes in optimal orientation with electrode movement across the striate cortex. In addition, relatively consistent differences were observed in the rates and patterns of orientation shift on these penetrations depending on the direction of electrode movement across the cortex. Penetrations parallel to the 17--18 border yielded moderate-to-high rates of orientation change (mean slope = 434 degrees/mm), with the changes generally progressing through a complete clockwise or counterclockwise cycle of 180 degrees or more before a major reversal in the direction of orientation shift was encountered. In contrast, penetrations perpendicular to the border yielded low-to-moderate slopes (mean slope = 239 degrees/mm). On these penetrations a more limited range of optimal orientations (< 180 degrees) was usually encountered, due to frequent reversals in the direction of orientation shift. Also, extended regions (100--200) micrometers long) of constant optimal orientation were observed in these penetrations. The different patterns of orientation change found on these orthogonal penetrations across the striate cortex indicate that the orientation column system in this species is anisotropically organized with respect to the 17--18 border. Further, the regions of constant optimal orientation frequently encountered on penetrations perpendicular to the 17--18 border suggest that the anisotropy is subserved by a system of elongated zones of iso-orientation arranged approximately perpendicular to the 17--18 border.

Animals↗

Topographic organization of the orientation column system in the striate cortex of the tree shrew (Tupaia glis). II. Deoxyglucose mapping.

The topographic organization of the orientation column system in the tree shrew striate cortex was examined by using 2-deoxyglucose autoradiography to map the cortical sites of increased metabolic activity produced by visual stimulation with stripes of a single orientation. Awake experimental tree shrews (freely moving, restrained, or paralyzed) were given injections of deoxyglucose label and then stimulated with vertical, horizontal, or oblique stripes for 45--75 min. Autoradiographs of coronal sections through the striate cortex revealed regularly spaced radial zones of increased deoxyglucose uptake 150--350 micrometers wide, extending from the cortical surface to the white matter, separated by interzone regions of lower uptake. The radial zones were most densely labeled and distinct in layers I--IIIb and least distinct in layer IV, which was continuously and densely labeled throughout both the radial zone and interzone regions. These radial zones, which were not present in control animals that viewed many orientations, reflect the locations of cortical cells activated by a single stimulus orientation. Reconstructions of the radial zones from serial sections produced maps of the distribution of increased deoxyglucose uptake across striate cortex. The maps reveal a highly organized system of narrow, parallel bands that are slightly wavy and have a mean spacing of 530 micrometers. The band pattern was confirmed in sections cut tangential to the cortical surface and was similar in animals stimulated with either vertical or horizontal stripes; the bands consistently abut the 17--18 border at nearly right angles and extend across the striate cortex in a generally posteromedial direction. These patterns of increased deoxyglucose consumption confirm the anisotropic distribution of orientation-selective cells across the tree shrew striate cortex, suggested in the preceding microelectrode study (Humphrey and Norton, '80). The density distribution of label within the bands further suggests that the anisotropy is due to a system of parallel, somewhat wavy iso-orientation lines arranged roughly perpendicular to the 17--18 border.

Animals↗

Laminar origin of projections from the superficial layers of the superior colliculus in the tree shrew, Tupaia glis.

The laminar origin of the efferent projections from the superior colliculus to the pulvinar and to the dorsal and ventral lateral geniculate nuclei has been studied using the retrograde axonal transport of horseradish peroxidase. Following injections in either the dorsal or the ventral lateral geniculate nucleus, cells heavily labeled with the horseradish peroxidase reaction product are restricted primarily to the upper stratum griseum superficiale. These cells have small, fusiform somas with dendrites which extend dorsally and ventrally, perpendicular to the pial surface. In contrast, following injections in the pulvinar, cells labeled with reaction product are restricted primarily to the lower stratum griseum superficiale and to the most superficial part of stratum opticum. These cells typically have larger somas than cells in the upper stratum griseum superficiale, and often have dendrites which emerge horizontally from the cell body. When taken together with previous electrophysiological and anatomical studies, the present findings suggest that there is a laminar subdivision of the tree shrew stratum griseum superficiale, and that these subdivisions project selectively to different thalamic targets.

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