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Effects of dark-rearing on triphenyl phosphate-induced neuropathy in the visual system of the developing European ferret (Mustela putorius furo).

Results of a previous study in our lab (Tanaka et al., 1994) suggested that the onset of susceptibility to the organophosphorus compound triphenyl phosphite (TPP) in the developing ferret visual system might be closely related to eye opening and the onset of light stimulation. In order to explore this idea further, TPP was administered to ferret kits that had been raised for varying periods of time in total darkness to assess whether a delay in the onset of light stimulation to the visual system might also result in a delay in its susceptibility to TPP. Ferret kits were raised from birth either in total darkness or in open-sided sheds exposed to ambient light, injected subcutaneously with TPP (888 mg/kg body weight) at 5.5, 7.5, 9.5, or 21.5 wk of age, euthanized, and perfused transcardially with a 10% formalin-saline solution 4 d after injection. Brains were sectioned parasagittally at a thickness of 40 microm and subsequently processed with the Fink-Heimer silver impregnation technique to reveal the presence of degenerating axons and terminals, and with cresyl violet stain to delineate nuclear boundaries and cell soma morphology. Comparisons among degeneration patterns present in light-reared and dark-reared kits at the four ages examined revealed that the time of onset, extent, and density of TPP-induced axonal and terminal degeneration seen in the lateral geniculate nucleus and primary visual cortex did not differ significantly between light- and dark-reared groups, with the possible exception of dark-reared kits exposed to TPP at 7.5 wk of age. In addition, neurons in the primary visual cortex showed shrinkage and increased packing densities in kits exposed to TPP in both light and dark environments, as well as in dark-reared non-injected kits. The results of this study indicate that dark-rearing does not delay the onset or lessen the severity of TPP-induced axonal and terminal degeneration in the developing visual system of the ferret. Data suggest that light activation and stimulation of the retino-geniculo-striatal visual pathway is not a necessary prerequisite for the onset of visual system susceptibility to the axonopathic effects of triphenyl phosphite.

Animals↗

Early visual experience, learning, and neurochemical plasticity in the rat and the chick.

Rats reared in the dark to 50 days show morphological and biochemical changes in the visual pathway. Light exposure results in elevated incorporation into protein in visual cortex, lateral geniculate and retina. Much of the visual cortex elevation is in a rapidly labelling, rapidly transported neuronal particulate protein. There are concomitant changes in lysosomal and transmitter enzyme activity. In chicks exposed to an imprinting stimulus (a flashing light) there are elevations in RNA polymerase and RNA and protein incorporation in the anterior forebrain roof (a.f.r.) compared with controls. There are changes in adenyl cyclase, cAMP and AChE. Behavioural controls show that although there are general biochemical sequelae of light exposure, the elevation in RNA synthesis in the a.f.r. is not a result of motor, stress or sensory activity, but is correlated with a measure of the learning of the stimulus characteristics. A model for neurochemical correlates of developmental plasticity, learning, and state-dependent transients is discussed.

Animals↗

Vision affects mushroom bodies and central complex in Drosophila melanogaster.

The brain of Drosophila is structurally altered by sensory stimuli that the flies receive during their adult life. Size and fiber number of the mushroom bodies, central complex, and optic lobes are influenced by social, spatial, or olfactory cues. Recently, the optic lobes have been shown to depend on the light regime that flies experience. Structural plasticity in the brain is thought to be a correlate of functional adaptations and long-term memory. We therefore extend our investigation of volume changes to the calyces of the mushroom bodies and the central complex. We show that rearing flies in constant light for 4 days increases the volume of both structures by up to 15% compared to rearing them in total darkness. Much of this difference develops during the first day. The effect of light is not hormonally mediated, as monocularly deprived flies develop a smaller ipsilateral calyx. Mutant analysis suggests that light generates its effects through known visual pathways. In contrast to the optic lobes, in the calyx and central complex structural changes can be linked to cAMP signaling, as in the mutants dunce1 and amnesiac1 no volume differences are observed. Surprisingly, the mutant rutabaga1 shows a prominent light-dependent volume increase in the calyx and central complex, dissociating structural from behavioral plasticity. In complete darkness wild-type flies grow larger calyces under crowded conditions in their normal culture vials than if kept in small groups on fresh food. This stimulating effect of crowding is not observed in any of the cAMP mutants, including rutabaga1.

Aging↗

A comparison of automated static dark stimuli with the Humphrey STATPAC program in glaucomatous visual field loss.

Visual field examination is conventionally performed with bright stimuli on a dark background. Dark stimuli on a bright background, however, may provide different information as light increases and decreases are subject to parallel processing in the visual pathway. Twenty five eyes with primary open angle glaucoma and visual field loss were examined with the Humphrey visual field analyser thresholding program 30-2 and the computer assisted moving eye campimeter (CAMEC) using static dark stimuli at four different Weber contrast levels of -10 (n = 9), -22 (n = 25), -37 (n = 14), and -76% (n = 25) on a cathode ray tube with a background luminance of 10 cd/m2. The cumulative results obtained with STATPAC 'pattern deviation' empirical probability maps and the results from each contrast of the dark stimulus at identical test locations were compared at eccentricity annuli bands of 4-9, 10-20, and 21-28 degrees. Dark stimuli of lower contrast provided higher abnormal point detection rates. Furthermore, visual field defects to the low contrast dark stimuli were more extensive than those to the luminous stimuli. In conclusion, dark stimuli allowed the delineation between glaucomatous field defects and the normal regions in the central visual field.

Adult↗

Neurophysiology of Rett syndrome.

Rett syndrome is a neurodevelopmental disorder that in most cases is consequent to a mutation in the MECP2 gene. The central nervous system is the primary organ system involved in Rett syndrome. Neurophysiologic evaluations provide information concerning the developmental aspects of Rett syndrome and the character and extent of involvement of the central, peripheral, and autonomic nervous system pathways. Evoked potentials typically demonstrate intactness of peripheral auditory and visual pathways and suggest dysfunction of central or "higher" cortical pathways. Somatosensory evoked potentials can be characterized by "giant" responses, suggesting cortical hyperexcitability. Cortical hyperexcitability is further suggested by the findings of the electroencephalogram (EEG), which are primarily characterized by a loss of expected developmental features; the appearance of focal, multifocal, and generalized epileptiform abnormalities; and the occurrence of rhythmic slow (theta) activity, primarily in the frontal-central regions. Epileptic seizures are reported to occur frequently in Rett syndrome. However, many events presumed to be seizures have no EEG correlate during video-EEG monitoring. Impairment of the autonomic nervous system in Rett syndrome is suggested by an increased incidence of long Q-T intervals during electrocardiographic recordings and diminished heart rate variability. Autonomic nervous system dysfunction can contribute to the increased incidence of sudden unexpected death in Rett syndrome.

Afferent Pathways↗

Pattern visual evoked potentials in pseudotumor cerebri. A longitudinal study.

The prognosis of "benign" intracranial hypertension (Pseudotumor cerebri) is generally favorable. In fact, the resolution of the clinical picture is related to the disappearance of the increased intracranial pressure. However, sometimes an irreversible visual loss can occur. The authors studied, over a period of time, seven subjects suffering from pseudotumor cerebri utilizing pattern visual evoked potentials (VEPs). Five patients showed normal VEPs latencies that remained such in the successive controls. Two patients displayed pathological P100 VEPs latencies. Such findings tended towards a progressive transient improvement following decompressive lumbar puncture. The authors suggest that the VEPs alterations in these patients could be due to the association of general (increased CSF pressure) and local (malformations, scleral canalis constrictions) ocular factors. In these circumstances, the pattern VEPs recordings could be coupled with traditional methods of evaluation of visual pathway damage capable of provoking an irreversible compromission of the visual function.

Adolescent↗

Organization of the ectostriatum based on afferent connections in the zebra finch (Taeniopygia guttata).

In birds with laterally-located eyes, such as zebra finches and pigeons, the tectofugal visual pathway is the most prominent route from the retina to the telencephalon. However, little is known about exactly how the visual information is processed in this pathway, especially at the core region of the ectostriatum (Ec) in the telencephalon. In order to reveal a detailed organization of Ec, we decided to systematically analyze the afferent connections of Ec by injecting small amounts of sensitive tracers (biotinylated dextran amine and cholera toxin subunit B) selectively into different regions of Ec and the thalamic center of the tectofugal pathway (the nucleus rotundus, Rt). The present study revealed a clearer picture of the organization of Ec subdivisions than previously known. The present results showed that the anterior portion of Rt sent a heavy projection to the ventral region of the anterior Ec, whereas the more caudal subdivisions of Rt sent projections to more caudal and dorsal portions in Ec. The results suggest that Ec subdivisions appear to be arranged along an axis 'rotated' in the anterior direction, almost parallel to other major telencephalic laminae. These results may clarify the physiological and chemical heterogeneity of Ec found in the previous studies. The present findings also provide an insight into the possible organization of a visual processing center in a non-mammal.

Afferent Pathways↗

Stimulus frequency affects c-fos expression in the rat visual system.

We have characterised the c-fos expression patterns in various centers of the visual pathway of adult rats monocularly stimulated either by continuous or flickering light at different frequencies. Results show different immunocytochemical patterns in all centers studied, the geniculate lateral complex (LGC), superior colliculus (SC) and primary visual cortex (Oc1), depending on the physical characteristics of the stimulus (blinking frequency and light wavelength). After stimulation of the left eye, the ipsilateral pathway presents a substantial density of immunoresponsive cells, which is greater than expected with respect to the number of fibers that project ipsilaterally from the retina to the LGC and the superficial layers of the SC. A surprisingly high positive immunoresponsiveness is obtained in all cases with coherent light stimulation in the red spectrum (634 nm).

Animals↗

[Activity of 3-neuron cortical microsystems in the cat during conditioned reflex switchover].

Multiunit activity in two projection cortical areas (visual and motor) was studied in cats at conditioned switch-over of defensive and alimentary responses to electrostimulation of the visual pathways. Interneuronal relations of three-neuronal cortical microsystems (intra-analyzer connections) and relations between microsystems in the visual and motor cortical areas (inter-analyzers connections) were analysed by the method of crosscorrelation of action potential trains. Similar interneuronal relations were revealed in the motor microsystems and different relations were found in visual ones at elaboration of conditioned switch-over. This apparently indicates the leading role of the cortical projection of the signal stimulus in integration of adaptive behavioural act. On the other hand, the presence of common bonds for alimentary and defensive situations as well as of specific ones for each of them was shown in the distribution of interneuronal connections between the analyzers. The former apparently provide for the realization of the conditioned effector movement of the animal occurring in both situations with participation of the same effector organ (the tongue) The latter determine the character of the specific adaptive reaction.

Animals↗

Transient and sustained components of the pupillary responses evoked by luminance and color.

That the pupil reacts to changes in luminance and color, as well as to spatial features in the retinal image raises questions about whether phasic and tonic and/or color and luminance visual pathways project to the pretectal pupillomotor neurons. The present study compares pupillary responses evoked by heterochromatic and achromatic luminance increments to investigate whether the pupillary responses evoked by color and by luminance are independent of one another. Principal component analysis is used to examine the constituents of the pupil responses. The results support the belief that the visual input to the pupillomotor system is organized into phasic and tonic (but not necessarily independent color and luminance) pathways.

Adult↗

Abnormal motion processing and binocularity: infantile esotropia as a model system for effects of early interruptions of binocularity.

Infantile esotropia, a common form of strabismus with onset prior to 6 months of age, occurs at a time of rapid visual development. While monocular visual acuity is relatively unaffected in these patients, the majority of them fail to achieve fully normal stereopsis. In addition, these patients show a spectrum of abnormalities in their ocular following responses, visual perception and visual evoked potentials (VEPs) that suggest a failure to develop a normal complement of motion processing mechanisms. While abnormalities of of stereopsis have been studied for many years, motion processing in strabismus is a rapidly evolving area of current research. Motion mechanisms are normally binocular and may form a distinct binocular sub-system. This review summarises which is known about sensory and motor abnormalities in infantile esotropia, with special emphasis on recent motion VEP recordings. The monocular motion VEP shows directional biases early in infancy that are consistent with a nasalward/temporalward response bias. Patients with infantile esotropia maintain their neonatal biases beyond the age at which they normally disappear. The motion VEP biases persist into visual maturity in patients whose strabismus is treated after about 2 years of age. Treatment prior to age 2 can lessen the magnitude of the motion VEP asymmetry and these improvements can be maintained into visual maturity. A recording from the striate cortex of a visually deprived macaque monkey indicates that the motion VEP asymmetry arises early in the visual pathway.

Esotropia↗

[Transient and steady-state electroretinograms and visual evoked potentials to pattern and uniform-field stimulation in humans].

I recorded simultaneously transient and steady-state electroretinograms (ERGs) and visual evoked potentials (VEPs) in response to pattern and uniform-field stimulation in 21 normal subjects, in order to study their physiological characteristics. ERGs and VEPs to pattern stimulation (P-ERGs and P-VEPs, respectively) showed different physiological features from those to uniform-field stimulation (U-ERGs and U-VEPs, respectively). With transient stimulation at a rate of 1Hz for both pattern and uniform-field stimulation, the b-wave latency of U-ERG tended to be shorter than that of P-ERG, while the P100 latency of P-VEP was significantly shorter than that of U-VEP. With steady-state stimulation at a rate of 4Hz for pattern stimulation and of 8Hz for uniform-field stimulation, the phase analysis revealed the first (1F) and the second (2F) harmonics as stable components for the U-ERG and U-VEP, while only 2F harmonic was a stable component for the P-ERG and P-VEP. The phase values of these components were different each other, and the maximal amplitude of the ERGs was shown by the 1F of U-ERG while that of the VEPs was shown by the 2F of P-VEP. These results suggest that the pattern and uniform-field stimulation allows us to separate pattern (contrast)-specific responses from luminance-specific responses both in ERGs and VEPs. Four patients with optic atrophy showed normal U-ERG while all of them showed abnormal P-ERG, U-VEP and P-VEP except one, who showed normal U-VEP. P-ERGs and P-VEPs may offer the information about the proximal inner retinal layer (or the ganglion cells) and the contrast channel of the visual cortex. U-ERGs and U-VEPs may be useful in evaluating the functions of the preganglionic cell activity in the retina and the luminance channel of the visual cortex. Therefore, simultaneous recording of ERGs and VEPs to pattern and uniform-field stimulation under both transient and steady-state conditions increase the diagnostic value of electrophysiologic testing in the visual pathways.

Adult↗

Beta activity: a carrier for visual attention.

The alpha (8-13 Hz), beta (15-25 Hz) and gamma (30-60 Hz) bands of the EEG have been long studied clinically because of their putative functional importance. Old experimental results indicate that repetitive stimulation of the visual pathway evokes synchronous responses at the cortical level with a gain that depends on frequency; oscillations within relevant bands are less damped at subsequent processing levels than others. Our current results show in the cat that cortico-geniculate feedback has a build-in potentiation mechanism that operates at around the beta frequency and activates thalamic cells thus lowering the threshold for visual information transmission. We have also shown that enhanced beta activity is propagated along this feedback pathway solely during attentive visual behavior. This activity consists of 300-1,000 ms bursts that correlate in time with gamma oscillatory events. Beta-bursting activity spreads to all investigated visual centers, including the lateral posterior and pulvinar complex and higher cortical areas. Other supporting data are discussed that are concerned with the enhanced beta activity during attentive-like behavior of various species, including humans. Finally, we put forward a general hypothesis which attributes the appearance of oscillations within the alpha, beta and gamma bands to different activation states of the visual system. According to this hypothesis, alpha activity characterizes idle arousal of the system, while beta bursts shift the system to an attention state that consequently allows for gamma synchronization and perception.

Animals↗

Pathology of the optic nerve and visual association areas. Information given by the flash and pattern visual evoked potential, and the temporal and spatial contrast sensitivity function.

Spatial and temporal contrast sensitivity functions (CSF) were compared with visual evoked potentials (VEP) in two groups of patients with pathology selectively affecting different parts of the visual pathway. These consisted of 10 patients with a selective delay of the pattern VEP due to demyelination of one optic nerve (unilateral optic neuritis) and 11 patients with a selective delay of the flash VEP due to pathology of the visual association areas (primary presenile dementia, or Alzheimer's disease). The results led to the following conclusions. Comparison of the VEP and CSF results indicated that VEP latency was more closely associated with the temporal CSF than the spatial CSF. Pathology of the visual association areas which selectively increased the latency of the flash P2 component also reduced sensitivity at low and medium temporal frequencies. In demyelination of the optic nerve, a highly significant correlation was found between the delay of the pattern reversal VEP and sensitivity at high temporal frequencies. Comparison of the results in these two types of pathology suggests that the pattern VEP and flash P1 component, the spatial CSF, and temporal CSF at high temporal frequencies are all processed in the geniculostriate pathway. The flash P2 component and temporal CSF at low and medium frequencies were affected differently from the other measures. The possibility that these processes are transmitted by nongeniculate pathways is discussed.

Adult↗

The effect of levodopa treatment on the visual evoked potentials in Parkinsonian patients.

There is extensive literature on the effects of levodopa treatment on the visual evoked potentials (VEP) in laboratory animals and in depressed patients. The effects of levodopa on the VEP of parkinsonian patients were overlooked to a certain extent. In this work we searched for levodopa effects on the VEP of 42 parkinsonian patients. The VEP were data-reduced and analyzed by several techniques: (a) 256 data values (256 msec) were reduced to 70 variables by averaging; (b) time-domain parametric extraction: latencies to peak-and-trough points, amplitudes, etc., resulted in 14 variables; (c) frequency transformation into power spectral density bands resulted in 14 variables. Each one of the above variables was univariate, paired t-tested for levodopa effects. The overall effects of levodopa on the power variables and the time-domain parameters were evaluated by Hotelling paired T2. The 70 time variables were further reduced by the tolerance function of the discriminant procedure and analyzed both by direct and by stepwise discriminant analyses and by SAS-MANOVA in a pairwise design. Only few sporadic univariate t values reached significance levels. No overall multivariate significant effects of levodopa were found. In view of known dopaminergic involvement in parts of the visual system it is postulated that levodopa might have antagonizing effects at different levels of the visual pathways. This hypothesis and better understanding of levodopa effects on the visual system should probably be achieved by recording VEP from the visual subsystems.

Evoked Potentials↗

Efficacy and safety of memantine, an NMDA-type open-channel blocker, for reduction of retinal injury associated with experimental glaucoma in rat and monkey.

Glutamatergic excitotoxicity has been implicated as a mechanism for injury in a variety of central nervous system pathologies, including glaucoma. Memantine, an NMDA-type glutamatergic open-channel blocker, has pharmacologic properties that make its efficacy greater under excitotoxic conditions, but lesser under normal conditions. Daily oral dosing for approximately 15 months with 4.0 mg/kg memantine in monkeys yielded plasma concentrations similar to those found in patients who received memantine treatment for Parkinson's disease. This same dose of memantine was not associated with any evidence of an effect on the normal function of the retina and central visual pathways, as indicated by measures of the electroretinogram (ERG) and visually-evoked cortical potential (VECP). Amplitude of the VECP response was reduced in eyes with experimentally induced glaucoma. When compared to vehicle-treated control animals, memantine-treated glaucoma eyes suffered significantly less reduction of VECP amplitude. Preliminary results in a rat model for experimental glaucoma also show that, when compared to control animals, systemic treatment with memantine (10 mg/kg/day) was associated with a significant reduction in glaucoma-induced loss of retinal ganglion cells.

Animals↗

Abnormal visual adaptation to flicker in multiple sclerosis.

A visual psychophysical adaptation procedure was used on patients with Multiple Sclerosis (MS) in an attempt to induce a temporary and local exacerbation of subclinical visual impairment. Using a flicker detection task, sensitivity before and after adaptation to a flickering stimulus was measured in 9 MS patients and 9 control subjects. Although only 22% of patient eyes had abnormal flicker sensitivity prior to adaptation, visual deficit was observed in 83% of eyes studied after adaptation. Of the 7 MS eyes studied for which no other sign or symptom of visual involvement was present, 5 were found to have visual deficits after flicker adaptation. In addition, 10 of the 11 eyes affected by MS showed an abnormal response to flicker adaptation. Recovery from the effects of adaptation was complete in all patients within 2 minutes. The results suggest that partial demyelination of visual pathway neurons may exist in patients without signs or symptoms of visual involvement. The prolonged stimulation provided during adaptation may produce a temporary fatiguing or conduction blockade of such neurons which may lead to reductions in sensory sensitivity.

Adaptation, Physiological↗

A visual field abnormality: ocular or cerebral cause?

The visual field can be affected by disorders involving any part of the visual pathway, from the retina to the striate cortex. The pattern of visual field damage can indicate the location of the disorder. The case is presented here of an 8-year-old girl with congenital glaucoma. Initial perimetry appeared consistent with glaucomatous field loss; however, this evolved into a homonymous quadrantanopia, indicating the presence of a cerebral lesion as the cause. Computed tomography and magnetic resonance imaging scans detected a large middle cranial fossa arachnoid cyst. Postoperatively there was resolution of the visual field defects secondary to the arachnoid cyst. The pattern of field loss was pivotal in this patient's management. Attention must be paid when caring for the patient with a chronic disease to ensure that concurrent conditions are diagnosed.

Arachnoid Cysts↗