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Horseradish peroxidase (HRP) and HRP conjugated to wheat germ agglutinin (WGA-HRP) were used as anterograde tracers in the monkey visual pathways. In addition to known optic pathways, we observed labeled fibers which left the lateral terminal nucleus of the accessory optic system, traveled around the cerebral peduncle, and could be followed as far as the medial terminal nucleus.
Functional logic employed by the nervous system for information processing resides mainly in the wiring patterns among specific types of neurons. Therefore, detailed knowledge on neuronal networks is essential for understanding a wide range of brain functions. A powerful and long-awaited method for analyzing the neuronal connectivity patterns would be to deliver tracers selectively to specific types of neurons and at the same time to label transsynaptically their axonal target neurons. For this purpose, we took advantage of a unique property of plant lectin, wheat germ agglutinin (WGA), which has been used as a transsynaptic tracer in classical neuroanatomical studies. We developed a novel genetic strategy that employs WGA cDNA as a transgene, for the visualization of selective and functional neural pathways in the nervous system. In this article, I will introduce several examples of neural pathways visualized with the WGA transgene and discuss about its further refinement and applications.
1. Experiments are described in which the phosphene produced by passing alternating current of frequency 100 Hz through the eye is matched with a patch of light having the same apparent size.2. Matches of this type have been made against different background light intensities, and at various times after a strong retinal bleach.3. To match the phosphene under particular conditions of this type, it is found that the patch must be set some 1.5 log td brighter than its own threshold under the same conditions. Exceptions to this rule occur with very bright backgrounds, or very soon after bleaching.4. The increment threshold for a small spot of light on the phosphene in the dark is some 0.5 log td higher than for the same spot on a patch of light matched in appearance to the phosphene under the same conditions.5. The process linking electrical stimulation of the eye to firing of fibres in the optic nerve is deduced to be substantially unaffected by the state of adaptation of the eye, save perhaps in the exceptional conditions described in (3).6. It is therefore argued that this phosphene is the result of stimulation both of the retinal visual pathways lying central to the variable-gain element commonly accepted to explain the facts of dark adaptation, and also of the input to this element that is supposed to alter its gain.
A unilateral intravitreal inoculation of herpes simplex virus type 1 (HSV-1) induced bilateral retinitis and encephalitis in the rat. Immunohistochemistry was employed to clarify the pathway of transmission of HSV-1 from the inoculated eye to the contralateral eye, and to identify localization of the viral antigen in the retina, optic nerve and brain. At an early stage of the post-inoculation period, HSV-1 immunoreactivity was first seen in the cytoplasm of Müller cells and then in various cells of the inner nuclear layer in the inoculated eye. At a later stage, HSV-1 immunoreactivity was seen in some retinal ganglion cells and optic nerve fibers in the inoculated eye. In the brain, HSV-1 was found in the optic chiasm, bilateral primary visual centers (bilateral suprachiasmatic nuclei, bilateral lateral geniculate nuclei, bilateral superior colliculus and bilateral pretectum) and bilateral visual cortex. HSV-1 was also demonstrated in the retinal ganglion cells, neural cells in the inner nuclear layer, and Müller cells in the contralateral eye. We found that HSV-1 antigen in the retina of the contralateral eye was transmitted through the optic nerve, visual pathway and nuclei, but not through the blood stream.
In multiple sclerosis (MS), an increase in delay in visual evoked responses (VER) may be important, but an earlier change is the behaviour of the wave-shape; amplitude is always lower even in MS patients without subjective visual symptoms, provided not only flash but also pattern stimulation is used. Normal amplitude with pattern stimulation does not necessarily mean normal amplitude with flash stimulation. Combining both stimulation methods, we found lowering of amplitude and change of wave-shape in 100 per cent of cases while latency was increased in only 77 per cent. Flash and pattern VER might be even more pathognomonic in MS than oligoclonal gammaglobulin fractionation on agar, which is positive in 75 per cent of cases. We recommend that subclinical cases of MS should be submitted to full electro-oculographic investigation. Patients with sectoral ischaemic neuropathy and open angle glaucoma (OAG) show the same findings; this emphasizes that the method is not specific for demyelinating diseases, nor selective for papillo-macular bundle involvement, but that VER, considering only its first components, reflects axonal damage somewhere in the visual pathway.
BACKGROUND: Relative afferent pupillary defects are typically related to ipsilateral lesions within the anterior visual pathways. OBJECTIVE: To describe a patient who had a workup for headache and was found to have an isolated left relative afferent pupillary defect without any other neurological findings. DESIGN: We review the neuroanatomy of the pupillary light reflex pathway and emphasize the nasotemporal bias of decussating fiber projections, which accounts for the relative afferent pupillary defect contralateral to the described lesion. Result Magnetic resonance imaging of the brain revealed a pineal tumor compressing the right rostral midbrain. CONCLUSION: While rare, a relative afferent pupillary defect can occasionally occur secondary to lesions in the postchiasmal pathways. In these circumstances, the pupillary defect will be observed to be contralateral to the side of the lesion.
The on-line visual control of human movements can be exceptionally fast. Whether it is fast depends on the kind of visual information that is involved. In the present study we examine whether fast on-line control is specific to the magnocellular visual pathway. Fast manual responses become evident when an ongoing movement has to be adjusted, for instance because the target is displaced. We examined whether the response to such perturbations is faster for stimuli that only activate the magnocellular pathway than for equally conspicuous stimuli that only activate the parvocellular pathway. The response was indeed about 35 ms faster for stimuli that activate the magnocellular pathway. However, we argue that the slower response to stimuli that only stimulate the parvocellular pathway is due to the properties of the neurones involved and the less direct connection to the motor areas, rather than to fast reactions being driven exclusively by magnocellular input.
The monoclonal antibody Rip recognizes an antigen specific to oligodendrocytes and their processes (Friedman et al: Glia 2:380, 1989). We have used this antibody to document the appearance of oligodendrocytes and the sequence of ensheathment of axons along the optic tract (OT) and within its major target areas in neonatal (P3-P21) and adult hamsters. Myelination of axons in the visual pathway follows an overall proximo-distal gradient. On P3, immunopositive, pre-ensheathing oligodendrocytes are detected in the OT ventral to the lateral geniculate body (LGB) whereas myelin segments are present around OT axons by P5. The first pre-ensheathing oligodendrocytes are detected medially in the LGB on P7 and myelinated axons in the overlying OT by P11. In the superior colliculus, pre-ensheathing oligodendrocytes are present in the optic fiber layer (SO) on P7, but not in the superficial gray layer (SGS) until P11. Myelination of axons within SO proceeds along a marked rostro-caudal gradient. On P14, axons in rostral SO are heavily myelinated; thereafter, ensheathment continues caudally within the SO and the SGS. The progressive invasion of oligodendrocytes along the proximo-distal axis of the optic pathway, and the corresponding myelination of OT axons, are discussed in the context of a possible inhibitory role of oligodendrocytes in regulating the regenerative propensity of retinotectal axons.
PURPOSE: To evaluate the effects of high-dose radiotherapy (RT) to the chiasm and optic nerves in locally advanced nasopharyngeal carcinoma patients by visual psychophysical and electrophysiologic tests. METHODS AND MATERIALS: A series of visual tests, including visual evoked potentials (VEPs), contrast sensitivity, and visual field and visual acuity tests, were administered to 27 patients with locally advanced (T4) nasopharyngeal carcinoma who had undergone RT to high doses 6 to 74 months previously. As a control group, the same tests were administered to 40 unirradiated patients who had been referred to the ophthalmology department for any reason. RESULTS: The median values of VEP latency, VEP amplitude, and contrast sensitivity and the rate of visual field defect were significantly worse in the RT group (p = 0.06, p <0.001, p <0.001, and p = 0.005, respectively). No dose-response relationship was found in any tests when 50 Gy was the cutoff value. However, a positive correlation between the interval after RT and VEP latency (r = 0.406, p = 0.003) and a negative correlation between the interval and contrast sensitivity (r = -0.499, p <0.001) was noted; no correlation could be established regarding VEP amplitude and the interval after RT. CONCLUSION: Radiation-induced injury to the anterior visual pathways could result in an increase in VEP latency and a decrease in VEP amplitude and contrast sensitivity. This injury seems to be a continuous process developing with time.
Visual acuity, the premier test of visual function, is analyzed as a three-stage, hierarchical sequence beginning with the detection of spatial contrast, followed by the resolution of that contrast into spatially separate elements, and ending with the identification of a particular arrangement of elements as one of several possible test objects, e.g., a letter in the Snellen alphabet. Each stage in this process has its own inherent limitations which are associated with different stages of the visual pathway. New methods are described for testing each stage of the hierarchy individually for the purpose of identifying the weak link in the chain, thus paving the way for differential diagnosis of optical and neural losses of vision.
BACKGROUND: Dyslexia is a common disorder that has traditionally been treated as a homogeneous condition. However, recent evidence indicates that it is a heterogenous condition with several subtypes. For example, studies of the visual system indicate that not all dyslexics have a normal visual pathway. Approximately 75% have a processing deficit in the magnocellular pathway. Our previous study indicated that dysphoneidetic but not dyseidetic dyslexics exhibit a magnocellular pathway defect. PURPOSE: The purpose of this study was to expand our previous work by also examining dysphonetic dyslexics. Additionally, the stimulus was altered to enhance detection of a magnocellular pathway defect in any dyslexic subtype. METHODS: Temporal contrast sensitivity functions were determined with a flickering stimulus (5, 10, 15, 20, and 25 Hz) by using a temporal, two-alternative, forced-choice technique. RESULTS: The results indicate that the dyseidetic dyslexics do not have a magnocellular pathway defect, whereas the dysphoneidetics do. Furthermore, examination of the individual dysphonetics indicated that the more severely affected subjects also exhibited a magnocellular pathway defect. CONCLUSION: These results suggest that treatment strategies for dyslexics may need to be modified to take into account their specific subtype.
We compared the horizontal optokinetic reaction (OKR) and response properties of retinal slip neurons in the nucleus of the optic tract and dorsal terminal nucleus (NOT-DTN) of albino and wild-type ferrets (Mustela putorius furo). In contrast to pigmented ferrets, we were unable to observe OKR in albino ferrets during binocular and monocular viewing using random dot full field stimulation and electro-oculography (EOG). Observations during early postnatal life indicate that regular OKR is present in pigmented pups 3 d after eye opening but is absent at any stage during development in albino ferrets. Unilateral muscimol injections to inactivate all neurons in the NOT-DTN containing GABA(A) and GABA(C) receptors caused spontaneous horizontal nystagmus with slow phases away from the injected hemisphere in albino as well as in pigmented animals. Retinal slip neurons in the NOT-DTN of albino ferrets identified by antidromic activation from the inferior olive and orthodromic activation from the optic chiasm were well responding to intermittent bright light stimuli, but many showed a profound reduction of responsiveness to moving stimuli. The movement-sensitive neurons exhibited no clear direction selectivity for ipsiversive stimulus movement, a characteristic property of these neurons in pigmented ferrets and other mammals. Thus, the defect rendering albino ferrets optokinetically nonresponsive is located in the visual pathway subserving the OKR, namely in or before the NOT-DTN, and not in oculomotor centers.
Eye movements evoked by local electrical stimulation of the dorsal nucleus of the lateral geniculate body were analyzed in cats with extirpated visual cortex and in intact cats. The experiments were performed in alert cats. There were no differences between the obtained spatial characteristics of eye movements evoked by electrical stimulation in experimental and intact cats. These results suggest that visual cortical areas are not the main and necessary links in the chain for signal transmission (evoked by electrical stimulation of lateral geniculate body) from subcortical parts of the direct visual pathway to acting links of the oculomotor system. The possible pathways for transmission of information from the dorsal nucleus of the lateral geniculate body to structures of the oculomotor system are discussed.
Power spectral analysis (PSA) was performed on the visual evoked potentials (VEPs) to counterphased checkerboard stimuli from 98 eyes in 49 patients with multiple sclerosis (MS) and 54 eyes of 27 normal volunteers. Attenuation of high frequency components of the transient visual evoked potential was found in 53% of MS patients and 4% of controls. Loss of high frequency components was poorly correlated with prolonged latency (r = 0.346). The consideration of both PSA and latency of the VEP increased the percentage of MS patients exhibiting visual pathway conduction abnormalities from 61% to 86%. The use of PSA in the diagnosis of MS is useful in increasing detection especially in cases where deformed waveforms preclude a reliable estimation of latency.
Anatomically distinct parvo and magno visual pathways show considerable functional overlap. However, specific stimulation of the most sensitive colour-opponent parvo-neurones is still possible, provided that colour stimuli are verified for selectivity. The authors have shown that gratings of low contrast, low spatial frequency and of restricted spatial content (6 or less spatial cycles) are optimal stimuli for distinguishing between colour-related (tritan and red/green) from achromatic or partly chromatic responses. This is particularly important when recording global responses, such as visual evoked potentials, VEPs. The crucial point is that at low presentation rates (< 2 Hz), colour-related onset VEPs are maximally different from contrast reversal VEPs, thereby reflecting the activity of sustained-type parvo mechanisms. Achromatic onset, offset and reversal VEPs are similar, reflecting mediation by transient-type magno mechanisms. A stringent test of colour-response specificity is to check whether the chromatic reversal VEP has a low-pass temporal tuning curve, since it becomes band-pass when substantial achromatic intrusions are present. Specification of chromatic isoluminant stimuli, e.g. along cardinal axes, does not guarantee their colour-selectivity, if chromatic aberration and variable macular pigmentation changes the chromatic content of the retinal image. It is shown here how chromatic stimuli, namely (1) red/green and (2) purple/green (tritanopic) gratings, can be optimized for selective stimulation of the colour system.
There is evidence that the cortical anatomy of the magnocellular (M) visual pathway, which carries information about motion and luminance contrast, was modified in human evolution. Recent results indicate that layer 4A of humans contains a meshwork of tissue bands that stain densely for nonphosphorylated neurofilament (NPNF), a protein that is preferentially expressed in elements of the M pathway, whereas apes and monkeys lack a comparable pattern. Here we examined the distribution of staining for Cat-301 -- a monoclonal antibody well established to stain M-related structures preferentially -- in area V1 of humans, apes (chimpanzees, orangutan), Old World monkeys (macaques) and New World monkeys (spider monkeys, squirrel monkeys). Single-staining experiments, using a peroxidase-tetramethylbenzidine (TMB) reaction, revealed alternating zones of dark and light staining for Cat-301 in layer 4A of humans, similar to those observed with NPNF. Double-staining studies in humans revealed that Cat-301-immunoreactive somas and neuropil were localized within the same tissue bands that stained strongly for NPNF and, furthermore, that these bands alternated with irregularly shaped territories that stained very strongly for calbindin. Nonhuman primates, by contrast to humans, displayed weak Cat-301 and calbindin staining in layer 4A. The co-localization of Cat-301 and NPNF in human layer 4A, and the weak staining for these molecules in layer 4A of other primates, suggests that the cortical representation of the M channel was modified in recent human evolution. The calbindin-rich compartments in human layer 4A cannot be related to a particular geniculostriate pathway on neurochemical grounds; they may constitute an interneuronal population that increased in human evolution.
Proper examination of the pupil provides an objective measure of the integrity of the pregeniculate afferent visual pathway and allows assessment of sympathetic and parasympathetic innervation to the eye. Infrared videography and pupillography are increasingly used to study the dynamic behavior of the pupil in common disorders, such as Horner's syndrome and tonic pupil.
The retina and optic nerve head have been examined by light and electron microscopy in adult Xenopus laevis after injury to optic nerve fibres. Intraorbital resection, transection or crush of the optic nerve all resulted in the appearance at the retina of a mass of actively growing axons which formed a ring around the intraretinal and adjacent choroidal portions of the optic nerve head. Formation of this heterotopic axon population was first noted at two weeks after nerve injury and fibres persisted for at least six months. The ectopic fibres were separated from the optic nerve head by astrocytes within the retina or by blood vessels and fibroblasts of the leptomeninges at extraretinal locations. In general, the orientation of the ectopic fibres was perpendicular to the fibres of the optic nerve. Bundles of axons were found between the ring of ectopic fibres and the pigment epithelial layer of the retina or among the blood sinuses of the choroid. Similar ectopic fibres were seen following transection of the optic nerve at the chiasm and after tectal ablation although the onset of these changes was slower than that seen after nerve resection. It is concluded that damage to visual pathways in the frog induces dramatic morphological alterations in the optic nerve and retina far proximal to the site of injury in this regenerating system.