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Quantitative light- and electron-microscopic analysis of cytochrome-oxidase distribution in neurons of the lateral geniculate nucleus of the adult monkey.

The distribution of cytochrome oxidase (CO) in the lateral geniculate nucleus (LGN) of normal adult macaque monkeys was analyzed in quantitative light- and electron-microscope (EM) studies. Both reactive and nonreactive neurons were found throughout laminae 1-6. Darkly reactive neurons were more numerous in laminae 1, 2, and 6. Within each lamina, there was a positive correlation between cell size and level of CO activity in neurons. The cell density was greater in laminae 1, 4, and 6, which received input from the contralateral eye, than in corresponding laminae representing the ipsilateral eye (2, 3, and 5). The cell density in each of the magnocellular laminae was less than that in each of the parvicellular laminae. Three types of neurons could be distinguished within magnocellular laminae at the EM level. Types I and II were interpreted to be relay neurons, while the small size of type III qualified them to be interneurons. Two populations were found within parvicellular laminae, corresponding to relay neurons and interneurons, respectively. EM quantitative analyses revealed that the darkly reactive neurons contained a high proportion of moderate to darkly reactive mitochondria, which comprised 44.2%, 42.5%, and 39.2% of the mitochondrial population within neurons of laminae 1, 2, and 6 respectively. In contrast, a relatively low proportion of reactive mitochondria were found in neurons within laminae 3 (22.8%), 4 (26.4%), and 5 (32.4%). Moreover, magnocellular laminae contained a higher density of synapses on cell bodies than parvicellular laminae. All laminae, except layer 5, contained predominantly symmetric synapses on cell bodies. However, the proportion of symmetrical synapses in the magnocellular laminae (65.6%) was greater than that in the parvicellular laminae (59%). Our quantitative light and EM results indicate that the level of metabolic activity in neurons of the monkey LGN is higher in magnocellular, ON-center, and contralateral than in parvicellular, OFF-center, and ipsilateral visual pathways, respectively. The metabolic activity of neurons is likely to reflect the chronic level of spontaneous and synaptically evoked discharges of these cells.

Animals↗

An autopsied case of Creutzfeldt-Jakob disease with the lateral geniculate body lesion showing antagonizing correlation between periodic synchronous discharges and photically induced giant evoked responses.

We reported an necropsy finding of a patient with Creutzfeldt-Jakob disease (CJD) who showed photo-stimulated giant spikes that simultaneously suppressed periodic synchronous discharges (PSD) and the loss of pupillary light reflex during the course of the illness. The necropsy revealed extensive gray and white matter lesions, and both the lateral geniculate body (LGB) and pregeniculate body were primarily affected. The superior colliculus, optic nerve and tracts were not affected. The cerebral cortices particularly of the occipital lobe were severely damaged. The Gennari line, however, was spared from lesion. The primary involvement of the LGB has been reported infrequently in CJD, however, it appears to be associated with the unusual electroencephalograph (EEG) feature of the present case. The pregeniculate lesion contributed to the loss of pupillary reflex. This finding indicates that the visual pathway may be involved in the mechanism of the generation of PSD in CJD.

Action Potentials↗

Visual evoked response asymmetry only in the albino member of a family with congenital nystagmus.

PURPOSE: To examine the purported relationship between visual fiber misrouting and congenital nystagmus (CN) by studying a family containing members with either hereditary CN alone or in conjunction with albinism. METHODS: Eight relatives in three generations of a family with two genetic disorders (congenital nystagmus [CN] and albinism) underwent complete ophthalmologic examination and visual evoked potential (VEP) assessment of visual pathway organization using a luminance flash and checkerboard pattern onset/offset stimulus paradigm. Age-matched controls patients (albino, CN, or normal) corresponding to the three affected family members underwent the same procedure. RESULTS: The standard VEP albino misrouting test did not reveal any signs of abnormality in all family members tested except for the clinically diagnosed 8-month-old albino proband patient. Visual evoked potential assessment from the albino patient evinced contralateral asymmetry characteristic of aberrant temporal retinostriate projections. CONCLUSIONS: Although CN and albinism share some of the same clinical symptoms, these findings indicate that the disorders may be inherited and manifested independently in members of one family. Furthermore, the functional and/or structural factors responsible for CN cannot be readily ascribed to VEP retinal-cortical misprojections recorded in albinism.

Adult↗

Mononuclear cell proliferation and hyperplasia during Wallerian degeneration in the visual system of the goldfish in the presence or absence of regenerating optic axons.

Patterns of proliferation and changes in non-neuronal cell number in the visual system of the goldfish have been quantitatively examined during optic axon regeneration after an optic nerve crush (ONC). In addition, in order to examine the effect of the regenerating axons on cellular responses in the visual pathways, we did a similar analysis of animals with the right eye removed (ER). Finally, we used double labeling protocols to demonstrate that the proliferating cells that we were counting were mostly phagocytic cells of the mononuclear lineage. In animals with an ONC, we observed an early burst of proliferation that peaked between 7 and 14 days after surgery in all parts of the visual system. In the optic tract, there was also a secondary rise that peaked at 21 days. Levels of proliferation returned to normal by 32 days postoperative in the tract and tectum, while they remained somewhat elevated in the optic nerve for at least 93 days. The total number of non-neuronal cells in the visual paths also rose to peak values between 7 and 14 days after ONC surgery. In the optic tract and tectum, the values fell rapidly after this time, while in the optic nerve, there was a secondary peak at 32 days after which values remained elevated for the duration of the experiment. As compared to animals with an ONC, enucleation resulted in elevated proliferation and hyperplasia at early postoperative intervals. However, because these differences occurred when axons had not yet regenerated into the affected structures, these data do not provide strong evidence for a direct effect of regenerating optic axons on the early cellular responses during Wallerian degeneration in the goldfish. In addition, in the tectum, there was an early increment in cell number that was not associated with elevated levels of proliferation. We believe that this increment represents immigration of resident microglia from other regions of the brain.

Animals↗

Neurovisual abnormalities preceding the retinopathy in patients with long-term type 1 diabetes mellitus.

BACKGROUND: Changes in the retina caused by diabetes may lead to visual impairment in dim light, even with good visual acuity and visual fields. To evaluate the visual abnormalities preceding the retinopathy in patients with type 1 diabetes mellitus (DM), we applied electrophysiological methods. METHODS: The visual evoked responses were recorded with sinusoidally modulated vertical gratings at 10 spatial frequencies presented sequentially on a high-resolution monitor in patients with type 1 DM and in normal volunteers. Similarly, the contrast visual evoked responses of 10 contrast levels were recorded at five spatial frequencies. Both amplitudes at the second harmonic were calculated by discrete Fourier transform. The visual acuity and contrast thresholds were determined objectively. RESULTS: There was dissociation between the Snellen and the estimated visual evoked response acuity measurements in patients with diabetes (r2=0.077, P=0.44). The saturation phenomena were observed at lower levels of contrast stimuli than in normal individuals at. 1.0, 2.0, 4.0 and 8.0 cycles per degree (P=0.0001). The contrast sensitivity function was deeply abnormal in all tested patients despite the metabolic control. The values of the area under the curve of the visual evoked response amplitude-contrast level function at five spatial frequencies were smaller in patients with DM than in the control group (P<0.05) at all spatial frequencies tested. CONCLUSIONS: Patients with type 1 DM without retinopathy showed significant lower amplitude of the visual evoked responses at all spatial frequencies tested, with the saturation phenomena observed at lower level of contrast stimuli. In addition, there was a dissociation between the sweep visual evoked responses and the Snellen acuity measurements. A significant and nonselective neuronal visual loss involving the visual pathway precedes the ophthalmoscopically detectable retinopathy in patients with type 1 DM.

Adult↗

Physiological properties of neurons in the optic layer of the rat's superior colliculus.

We made intracellular recordings from 74 neurons in the optic layer of the rat superior colliculus (SC). Resting membrane potentials were -62.3 +/- 6.2 (SD) mV, and input resistances were 37.9 +/- 10.1 MOmega. Optic layer neurons had large sodium spikes (74.2 +/- 12.3 mV) with an overshoot of 12 mV and a half-amplitude duration of 0.75 +/- 0.2 ms. Each sodium spike was followed by two afterhyperpolarizations (AHPs), one of short duration and one of longer duration, which were mediated by tetraethylammonium (TEA)-sensitive (IC) or apamin-sensitive (IAHP) calcium-activated potassium currents, respectively. Sodium spikes were also followed by an afterdepolarization (ADP), which was only revealed when the AHPs were blocked by TEA or apamin. In response to hyperpolarizing current pulses, optic layer neurons showed an inward rectification mediated by H channels. At the break of the current pulse, there was a rebound low-threshold spike (LTS) with a short duration of <25 ms. The LTS usually induced two sodium spikes (doublet). Most optic layer neurons (84%) behaved as intrinsically bursting cells. They responded to suprathreshold depolarization with an initial burst (or doublet) followed by a train of regular single spikes. The remaining 16% of cells acted as chattering cells with high-frequency gamma (20-80 Hz) rhythmic burst firing within a narrow range of depolarized potentials. The interburst frequency was voltage dependent and also time dependent, i.e., showed frequency adaptation. Unmasking the ADP with either TEA or apamin converted all of the tested intrinsically bursting cells into chattering cells, indicating that the ADP played a crucial role in the generation of rhythmic burst firing. Optic layer neurons receive direct retinal excitation mediated by both N-methyl--aspartate (NMDA) and non-NMDA receptors. Optic tract (OT) stimulation also led to gamma-aminobutyric acid-A (GABAA) receptor-mediated inhibition, the main effect of which was to curtail the excitatory response to retinal inputs by shunting the excitatory postsynaptic current. Intracellular staining with biocytin showed that the optic layer neurons that we recorded from were mostly either wide-field vertical neurons or other cells with predominately superficially projecting dendrites. These cells were similar to calbindin immunoreactive cells seen in the optic layer. The characteristics of these optic layer neurons, such as prominent AHPs, strong shunting effect of inhibition, and short-lasting LTS, suggest that they respond transiently to retinal inputs. This is consistent with a function for these cells as the first relay station in the extrageniculate visual pathway.

Animals↗

Chromatic sensitivity of ganglion cells in the peripheral primate retina.

Visual abilities change over the visual field. For example, our ability to detect movement is better in peripheral vision than in foveal vision, but colour discrimination is markedly worse. The deterioration of colour vision has been attributed to reduced colour specificity in cells of the midget, parvocellular (PC) visual pathway in the peripheral retina. We have measured the colour specificity (red-green chromatic modulation sensitivity) of PC cells at eccentricities between 20 and 50 degrees in the macaque retina. Here we show that most peripheral PC cells have red-green modulation sensitivity close to that of foveal PC cells. This result is incompatible with the view that PC pathway cells in peripheral retina make indiscriminate connections ('random wiring') with retinal circuits devoted to different spectral types of cone photoreceptors. We show that selective cone connections can be maintained by dendritic field anisotropy, consistent with the morphology of PC cell dendritic fields in peripheral retina. Our results also imply that postretinal mechanisms contribute to the psychophysically demonstrated deterioration of colour discrimination in the peripheral visual field.

Animals↗

Growth of optic tract axons in nerve grafts in hamsters.

Segments of peripheral nerve, transplanted to the brain or spinal cord, recently have been shown to support regeneration of axons from a variety of central neurons. However, long-tract axons, injured at considerable distances from their cell bodies, have proven refractory to such regenerative support. This report presents evidence for successful, although similarly limited, growth of retinal ganglion cell axons into peripheral nerve grafts placed in the optic tract of adult hamsters. The demonstration of such growth allows the possibility that the primary visual pathways may serve as an advantageous model system in which to study the mechanism of graft-effected regeneration of long-tract axons in the adult mammalian central nervous system.

Animals↗

Visual hallucinatory syndromes and the anatomy of the visual brain.

We have set out to identify phenomenological correlates of cerebral functional architecture within Charles Bonnet syndrome (CBS) hallucinations by looking for associations between specific hallucination categories. Thirty-four CBS patients were examined with a structured interview/questionnaire to establish the presence of 28 different pathological visual experiences. Associations between categories of pathological experience were investigated by an exploratory factor analysis. Twelve of the pathological experiences partitioned into three segregated syndromic clusters. The first cluster consisted of hallucinations of extended landscape scenes and small figures in costumes with hats; the second, hallucinations of grotesque, disembodied and distorted faces with prominent eyes and teeth; and the third, visual perseveration and delayed palinopsia. The three visual psycho-syndromes mirror the segregation of hierarchical visual pathways into streams and suggest a novel theoretical framework for future research into the pathophysiology of neuropsychiatric syndromes.

Aged↗

A long-term observation on a case of epilepsy with occipital continuous spikes.

We have reported a 38-year-old female who did not show clinical seizures during continuous spikes in the left occipital area over a period of 18 years. As to the neurological findings, visual disturbance, optic nerve atrophy and right hemianopsia were almost always present. The low density area distributing from the left occipital area to the left temporal one on the CT revealed to be porencephaly. From the clinical findings obtained in this case, the lesion responsible for the occipital continuous spikes could be ascribed to be functional abnormality of the visual pathway connecting the left lateral geniculate body with the left occipital cortex.

Adult↗

The sequential development of the higher visual centers in the C.N.S. of the quail.

The development of the optic tectum and the main nuclei of the visual pathways were studied in the quail and correlated with retinal development. The lateral geniculate nuclei began to establish by the 8th day of ineubation and the optic fibre reached the optic tectum by the 10th day, a time when the retina acquired its inner segments. By the 14th day when the retina became fully development, the cytological architecture in the tectum and the appearing of the other visual nuclei were completed.

Animals↗

Morphological aspects of the teleostean visual system: a review.

This review is concerned with results of research carried out in the last two decades regarding visual pathways and centers in teleosts. It covers neither morphology of the retina nor development and plasticity. The optic nerve is considered in terms of axonal composition and retinotopic organization. The connections to the retina and from the retina are subsequently reviewed, and a general scheme is proposed for the retinofugal targets in thalamus and pretectum. The tectum opticum is then reviewed as regards its afferent connections from retina, telencephalon, diencephalon, mesencephalon and brainstem, with details on distribution of terminals, cell types contacted and synaptic structure. The efferent tectal connections are reviewed next, including their plausible cells of origin. Finally, a general diagram of the teleostean visual system is presented, and several circuits within this diagram are emphasized and discussed.

Afferent Pathways↗

Visual evoked potentials and electroretinography in brain-dead patients.

Visual evoked potentials and electroretinograms were elicited by light-emitting diode stimulation and recorded simultaneously, with cephalic and noncephalic references, in 30 normal subjects and in 30 brain-dead patients. A characteristic pattern was found in the group of patients: when a cephalic reference was used for both visual evoked potentials and the electroretinogram, the a- and b-waves of the electroretinogram were recognized in all patients, and visual evoked responses consisted of waves with inverse polarity, similar morphologic characteristics, the same latency, and less amplitude than those of the electroretinogram. When a noncephalic derivation was chosen for the electroretinogram and visual evoked potentials, electroretinogram did not change in either morphologic features or latency, whereas the visual evoked potential channel showed no response. Only in two cases was it possible to record waves in the visual evoked potential lead with a noncephalic reference, showing a spread of the electroretinogram to the occipital area, with a considerably reduced amplitude. These results suggest that, although contamination of visual evoked potential records by the spread of the electroretinogram to the occipital area could occur, it is easy to confirm the absence of a true cortical visual response in brain-dead patients by means of a noncephalic reference. This pattern clearly confirms that in the visual pathways of brain-dead patients, electrical activity is confined to the retina.

Adolescent↗

Differential localization of N-acetylated indolealkylamines in CNS and the Harderian gland using immunohistology.

Using two different antisera, one binding only melatonin (M) and the other binding both M and N-acetylserotonin (NAS), brain tissue and the Harderian gland were investigated using fluorescence and peroxidase labeled double antibody immunohistology. M has been identified in the outer nuclear layer of the retina, in the optic nerves, chiasma and the tracts, suprachiasmatic nucleus and the Harderian gland. NAS, but not M, was found in the granule layer of the cerebellum, spinal tract of the trigeminal roots and the pontal and spinal reticular formation. The possible relationship of cerebellar and brain stem NAS to brain excitability as well as localization of M in the visual pathway, suprachiasmatic nucleus and the Harderian gland in the relation to the regulation of light dependent circadian periodicity is discussed.

Animals↗

Receptor and neural visual readaptation after exposure to colored flash.

The time needed to recover optokinetic nystagmus or electroretinography complexes after a glare inducing flash was measured to study the receptor and neural visual readaptation. Electroretinographs and optokinetic nystagmus were evoked with low intensity stimuli. The light from a flash tube was filtered with an interference filter (Tmax = 536 or 622 nm) and evenly distributed into a Goldmann hemisphere observed by the subject. The Recovery of the amplitude of the a-wave of the electroretinography is quicker than the recovery of optokinetic nystagmus after a low intensity glare inducing flash. The recovery time was shorter for a red than for a green flash of equivalent dose for both recovery modalities. The time difference between electroretinography a-wave and optokinetic nystagmus recovery was the same and independent of glare inducing flash wavelength. The recovery of the amplitude of the a-wave of the electroretinography was quicker than the recovery of optokinetic nystagmus after a low intensity glare inducing flash. This time difference between the recovery modalities may in part be due to the difference between the physiological stimuli used, but it is believed that most of the time difference is because the recovery of optokinetic nystagmus monitors more of the afferent visual pathway with complex post receptor neural mechanisms than the recovery of the a-wave.

Adaptation, Ocular↗

Myelin debris clearance during Wallerian degeneration in the goldfish visual system.

We have examined the clearance of myelin debris from the visual pathways of the goldfish during Wallerian degeneration. Both the rate and pattern of myelin disappearance from the optic nerve and tract were determined using immunohistochemistry on frozen sections, as well as plastic sections and electron microscopy. Animals with and without regenerating optic axons were examined in order to determine whether the axons play a role in myelin clearance. We found that myelin is cleared at different rates along the visual paths. Thus, virtually all myelin debris is gone in the optic tract and distal optic nerve stump by 4 weeks after surgery, while in the cranial nerve segment, myelin clearance is still incomplete at 6 weeks postoperative. These temporal and spatial patterns of myelin clearance are the same in animals with and without regenerating axons, thus indicating that growing axons do not influence this process. Finally, ultrastructural observations revealed that both astrocytes and microglia participate in phagocytosing myelin debris in the optic nerve, while in the tract, the vast majority of debris is removed by microglia alone. These data are discussed with regard to possible mechanisms controlling the differential expression of myelin clearance.

Animals↗

Immunohistochemical study of the pattern of rapid expression of C-Fos protein in the visual cortex of dark-reared kittens following initial exposure to light.

Brief alterations to the nature of the visual input during critical periods in the early life of cats and monkeys can result in rapid anatomical and physiological changes in the central visual pathways. The immediate early genes (IEGs) represent a possible way in which these changes could be mediated since the protein products of a number of these genes have been shown to be induced rapidly in neurons in response to a variety of transsynaptic stimuli. Immunohistochemical methods were employed to examine the tempo and pattern of expression of Fos, the protein product of the c-fos gene, induced in the visual cortex of kittens dark-reared from birth to 30 days of age by brief periods of binocular visual exposure. In visual cortical area 17, the number of Fos immunoreactive cells increased rapidly from virtually zero in control kittens that received no visual exposure, to reach high levels in animals that received between 1 and 2 hours of visual experience. Immunoreactive cells were absent in the dorsal lateral geniculate nucleus, but were numerous in the ventral lateral geniculate nucleus, and in area 17, were most numerous in the extragranular layers (2, 3 and 6) but sparse in lower layer 4 and layer 5, and virtually absent in layer 1. Substantial constitutive Fos immunoreactivity was observed in area 17 of normal 30-day-old kittens but very few immunopositive cells were evident in adult animals. However, Fos immunoreactivity was observed in the visual cortex of a dark-reared (for 30 days) adult animal following a brief period of visual exposure, a finding that suggests that Fos might serve other roles in the visual cortex in addition to those it might play uniquely during development. It is suggested that Fos, in combination with the protein products of a select number of other IEGs, may mediate a variety of rapid changes in the visual cortex including those that underlie visual system plasticity during early postnatal life.

Animals↗

[Clinical and experimental study of traumatic optic nerve damage].

BACKGROUND: Traumatic optic nerve lesions (TONL) range from temporary affection of vision to avulsion of the optic nerve; often they are associated with more complex injuries. Usually Tonl are not regarded as an emergency. Up to now, we lack knowledge on the dependency of strength and duration of optic nerve lesions and the point of no return for afferent disorders of the visual pathway. MATERIALS AND METHODS: We performed a prospective study on 50 patients with severe midface and skullbase fractures in order to find characteristic ophthalmological, computer tomographic und electrophysiological findings as indicators of TONL, independent of patient cooperation. We used an animal model (Wistar rats; n = 117) to study calibrated optic nerve lesions and the resulting neurodegeneration in the retinal ganglion cell (RGC) layer quantitatively. RESULTS: The electrophysiological investigation of the visual system (flash VEP/ERG) proved to be highly specific (0.97) and sensitive (1.0) for detecting TONL (n = 18). In the rat model, we could demonstrate a linear relationship between total neuron number reduction and strength and duration of calibrated optic nerve lesion. CONCLUSIONS: Experimental results indicate that optic nerve decompression is useful only within the first hours after TONL to reduce secondary optic nerve lesion. Indication for optic nerve decompression requires early detection of TONL, which is made possible by the combination of flash VEP/ERG.

Animals↗