The pattern electroretinogram in animals and humans: physiological and clinical applications.
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Biomedical subjects
Publications and source records attributed to L Maffei.
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1. Single-cell recordings were made in the magnocellular layer of the dorsal lateral genicule nucleus (dLGN) of five adult cats in which prenatal binocular interactions were interrupted by monocular enucleation at known gestational ages. Three cats (early enucleates) had one eye removed on either embryonic day 44.48, or 49, before retinogeniculate inputs are segregated into uniocular layers. Two other (late enucleates) underwent this procedure on embryonic days 55 and 58, when segregation is well advanced. Responses were compared with those obtained from recordings in the A and A1 layers of the dLGN of seven normal adult cats. 2. Cells were classified as ON or OFF by the use of spots of light and as X or Y based on a test of linearity of spatial summation with the use of counterphased sinusoidal gratings. Receptive-field size and spatial resolution were also obtained. 3. The dLGN of prenatally enucleated cats contains a dorsal magnocellular layer and a ventral parvocellular layer. In early enucleates, only an occasional hint of a cell-sparse interlaminar zone was apparent, located between the magnocellular and parvocellular layers. In late enucleates, a prominent cell-sparse band was observed contralateral to the remaining eye, in a region that would most likely correspond to layer A1 in the normal dLGN. No such cell-sparse band was seen ipsilateral to the remaining eye in late enucleates. 4. Eighty-six X cells and 22 Y cells were studied in the enucleates. Both cell types were found at all depths of the magnocellular layer. All but a few neurons had concentric ON-center or OFF-center receptive fields that were normal in size. The topography of receptive fields also appeared normal. In addition, spatial resolution of X and Y cells was similar in experimental and control animals. 5. In early enucleates there was a higher percentage of X cells and a lower percentage of Y cells than normal. The change in X-to-Y ratio was shown to be because of both a gain in cells with X properties and a loss of cells with Y properties. The distribution of dLGN somal sizes in the early enucleates was comparable with controls, so the change in X-to-Y ratio most likely did not result from an electrode sampling bias. It was suggested that the X-to-Y ratio difference could stem from the abnormalities in retinogeniculate terminal arbors that have been shown to follow early eye removal.(ABSTRACT TRUNCATED AT 400 WORDS)
The ability of NGF (2.5S subunit) to support the survival of adult rat retinal ganglion cells (RGCs) and optic nerve fibers after intracranial section of the optic nerve was investigated. NGF was injected intraocularly at a dose of 3 micrograms/injection every 2.3 d from the day of axotomy to analysis. Control animals received cytochrome c injections. The survival of RGCs was analyzed in whole-mounted retinas after either cresyl violet staining or labeling with HRP applied to the proximal stump of the optic nerve. Survival times were 5 and 7 weeks. Diameter distribution and number of myelinated optic nerve fibers were assessed in ultrathin cross sections of the optic nerve. We found that RGCs surviving axotomy were much more numerous following NGF treatment compared with controls. Large-size cells were, in particular, preserved by NGF treatment. The quantitative ultrastructural studies indicated that the number of myelinated optic nerve fibers at 5 and 7 weeks postaxotomy was significantly greater in the NGF group with respect to the cytochrome c group. In agreement with the results obtained at the level of the RGCs, large-diameter axons were, in particular, preserved. We conclude that NGF injected intraocularly is effective in promoting the survival of RGCs and optic nerve fibers at least for a period as long as 7 weeks after intracranial section of the optic nerve.
The existence of spontaneous neural activity in mammalian retinal ganglion cells during prenatal life has long been suspected. This activity could play a key role in the refinement of retinal projections during development. Recordings in vivo from the retinas of rat fetuses between embryonic day 17 and 21 found action potentials in spontaneously active ganglion cells at all the ages studied.
In wholemounted retinae of cat, rat and monkey, in which ganglion cells were retrogradely labelled with horseradish peroxidase, a quantitative analysis of the direction of the axon initial segment with respect to the optic disc and of the relationship between the axon initial segment and the direction and distribution of primary dendrites was performed on the class of largest ganglion cells. The results show the following. (1) In all 3 species, the majority of primary dendrites of ganglion cells are directed away from the axon initial segment. (2) Primary dendrites arise with a greater frequency from the region of the cell body opposite to the axon initial segment than close to it. (3) In cat the direction of the axon initial segments show less variance in their initial direction with respect to the optic disc than in rat or monkey. In adult cats the nucleus of alpha-ganglion cells occupies a central position. In the kitten the position of the nucleus is eccentric and lies in a part of the cell body opposite to the axon initial segment. The nucleus moves to a central position over the next 3 weeks. The position of the axon initial segment is discussed as a possible determinant of ganglion cell dendritic geometry.
A lesion to the retina of a newborn rat results in the retrograde degeneration of ganglion cells in a sector of retina peripheral to the lesion. The dendritic tree of ganglion cells bordering the region depleted of ganglion cells have their dendrites preferentially directed into this area. We have examined the factors which play a role in this rearrangement of the dendritic tree. The results show that the lesion in neonates selects for or produces a population of cells with the axon directed away from the depleted area and primary dendrites directed towards the depleted area. The abnormal dendritic bias cannot be accounted for solely on the basis of a decrease in contact inhibition since a reduction in the density of all ganglion cells by 30% prior to making the retinal lesion does not attenuate the abnormal dendritic bias into the depleted area. The abnormal dendritic bias is present in animals operated on up to 15 days of age postnatally but not in more mature animals. The abnormal dendritic bias develops prior to the formation of a large number of synapses in the inner nuclear layer. Our results cannot be easily accounted for by competition for synaptic contacts or a loss of contact inhibition as previously suggested. We propose that chemotropic factors produced within the area depleted of ganglion cells induce the abnormal dendritic bias and the number of synaptic contacts may limit the size of the dendritic field.
The spatial frequency tuning curves of neurones of area 18 depend upon the velocity of the visual stimulus. The higher the velocity the lower the spatial frequencies to which the cell is tuned. Since in area 17 the size of the cell receptive field is inversely related with the optimal spatial frequency to which the cell responds, we have investigated whether the shift of the optimal spatial frequency with the velocity corresponds to a "change" in the receptive field size. We recorded extracellularly from neurones in area 18; for each cell we selected two gratings, one of high spatial frequency drifting at low velocity and another of low spatial frequency drifting at high velocity to which the cell gave comparable responses. The results show that the masking of the cells receptive field which abolishes the response to the high frequency low velocity grating does not prevent the cell from responding to the low frequency high velocity grating. We conclude that the size of the receptive field of neurones in area 18 depends upon the characteristics (spatial frequency and velocity) of the visual stimulus.
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1. The spatial and temporal characteristics of the visual information transmitted across the corpus callosum have been studied in normal cats by recording directly from the corpus callosum and in split-chiasm cats by means of visual evoked potentials (v.e.p.s) and single-unit recordings at the 17/18 border. 2. The modulation transfer functions (m.t.f.s) obtained by recording from the corpus callosum are comparable to the m.t.f.s evaluated by various techniques for the whole visual system of the cat. The spatial and temporal acuities, however, do not reach the values obtained behaviourally or estimated with cortical evoked potentials. 3. In split-chiasm cats, both v.e.p.s and single-unit recordings indicate that the contrast gain of the callosal pathway is considerably lower than the gain of the direct, geniculo-cortical system. Spatial and temporal acuities are lower for the callosal than for the direct system. 4. The same differences in contrast gain between the spatial m.t.f. obtained for the callosal and the direct system have been found in alert split-chiasm cats. 5. Our data suggest that the cross-talk between the hemispheres taking place across the corpus callosum is nearly abolished at low contrasts and high spatial and temporal frequencies.
Stereoacuity was measured with an operant conditioning technique in adult cats with unilateral deafferentation of oculomotor proprioception (section of the ophthalmic branch of the fifth cranial nerve). Binocular stereoacuity was found not to exceed monocular depth sensitivity, in contrast to what is obtained in normal cats. The results confirm previous findings and indicate a role of oculomotor proprioception in binocular depth perception of the cat.
Dichoptic presentation of patterns similar in shape but of very different contrast results in the perception of only the high contrast pattern (binocular suppression). When recording from binocular neurons of the cat visual cortex, we have found an effect which is strikingly similar to this perceptual phenomenon. If a high and a low contrast grating are presented simultaneously, one to each eye, the cell's response to the low contrast stimulus is suppressed.
Responses to sinusoidal gratings for neurons in area 17 and 18 of split chiasm cats were recorded extracellularly, and the interocular transfer of the effect of adaptation to high-contrast gratings was studied. In area 17 all but one of the simple cells showed the phenomenon of adaptation and its interocular transfer; 60% of the complex cells showed the effect of adaptation, and of these cells 35% showed an interocular transfer of adaptation. The adaptation aftereffect was comparable both in strength and duration for the direct and the callosal pathway. The strength of the adaptation aftereffect through the callosal pathway was not related to the strength of the input from the contralateral eye. An interocular transfer of the adaptation aftereffect was found in several neurons with a very weak input from the contralateral eye and in five simple cells apparently responding only to the ipsilateral eye. Fifty-eight percent of the neurons in area 18 showed the effect of adaptation, and 55% of them showed interocular transfer. No interocular transfer of the adaptation aftereffect was found in those neurons where an input from the contralateral eye was undetectable. Interocular transfer of the adaptation was found in all the neurons recorded in area 17 of animals with section of the corpus callosum but intact chiasm. No interocular transfer was found in neurons recorded in area 17 of cats with both the optic chiasm and the corpus callosum sectioned. We conclude that callosal connections are sufficient for the transfer of the adaptation aftereffect, although they are not necessary.
Depth discrimination was tested behaviourally in adult cats prior to and after chronic section of the ophthalmic branch of the Vth cranial nerve, that contains the majority of oculomotor proprioceptive fibers. Binocular depth discrimination was considerably impaired following either unilateral or bilateral oculomotor proprioceptive deafferentation.
Electroretinographic responses (ERG) to homogeneous light flashes and to alternating gratings were recorded from either eye of monkeys in which one optic nerve had been previously sectioned. Three weeks after optic nerve section the ERG response of the operated eye to alternating gratings was drastically reduced in amplitude and 5 weeks after surgery it was reduced to noise level. The uniform field ERG was unaffected. Histological examination of whole-mounted retinas of monkeys sacrificed 6 and 8 weeks after optic nerve section showed a loss of ganglion cells in the operated eye. It is concluded that the integrity of ganglion cells is essential for the generation of a normal ERG response to gratings.
After intracranial transection of the optic nerve in cats the retinal stump of the nerve was injected with HRP. Surviving retinal ganglion cells can be retrogradely labeled at least up to 15.5 months of postoperative survival.
The functional consequences of interrupting in utero binocular interactions were studied by recording from single cells in area 17 of adult cats that had one eye removed at least 2 wk before birth. In these animals all cortical neurons could be driven by the remaining eye, and in tangential microelectrode penetrations, sequences of neurons containing a full 180-degree cycle of preferred orientations were encountered. Other response properties of cortical neurons in the prenatally enucleated animals were also normal with the notable exception that the dimensions of receptive fields were significantly smaller when compared with those of control animals. Our results indicate that orientation columns in the visual cortex can develop independently of ocular dominance columns, and they suggest that interruption of binocular interactions during prenatal development of the visual pathways may enhance the resolving power of the remaining eye.
The spatial and temporal response properties of neurones of areas 17 and 18 were studied in single units (165) of anaesthetized and paralysed cats. The visual stimuli were drifting or alternating gratings. We confirmed and extended the observation by Tolhurst & Movshon (1975) showing that the spatial-frequency characteristics of neurones of area 17 are largely independent of the temporal parameters of drifting or alternating gratings. The spatial-frequency tuning curves of neurones of area 18 shift along the spatial-frequency axis when the velocity or the temporal frequency of the drifting grating are changed. The effect of an increase either of velocity or temporal frequency is to shift the cell spatial-frequency tuning curve down the spatial-frequency scale, keeping relatively constant the strength and band width of the response. The spatial-frequency tuning curves of neurones of area 18 do not show this temporal-frequency-dependent phenomenon when the stimuli are gratings alternated in phase. In this case neurones of areas 17 and 18 show a similar behaviour. The response properties of neurones of area 18 are compared with recent psychophysical results obtained in similar experimental conditions. The hypothesis is advanced that both areas 17 and 18 are devoted to the processing of spatial information. Area 17 would be responsible for the processing of patterns in stationary or quasi-stationary situations while area 18 would be responsible for that of patterns moving at high velocities.
Effects of dopaminergic drugs (L-dopa plus benserazide, or nomifensine) on human visual function have been tested in healthy volunteers by measuring the psychophysical contrast sensitivity for sinusoidal gratings of various spatial frequencies. After drug administration the contrast sensitivity improved in all subjects over a limited range of medium to high spatial frequencies.