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PubMed1990

Chromatin structure and gene expression in Alzheimer's disease.

Light micrococcal nuclease digestion was used to examine DNA associated with nucleosome populations isolated from Alzheimer's disease (AD) affected superior temporal lobe neocortical nuclei. 46.1% of the immediate 5' upstream DNA sequence of the single copy neurofilament light chain (NF-L) gene was found to be associated with a mononucleosome fraction in control neocortices. This fraction was reduced to 7.4% in age-matched AD-affected neocortex. No differences in accessibility to the nuclease probe was found between AD-affected and control temporal grey matter nuclei for the human prion HuPrP gene or for the NF-L gene in nuclei isolated from the primary visual cortex or the cerebellum. An AvaI restriction endonuclease site, located 124 base pairs upstream from the TATAA box in the NF-L leader sequence, was also found to be occluded in AD-affected nuclei. From this and previous data we conclude that within the AD-affected nucleus, focused changes in neuronal chromatin conformation occur. Increases in the packing density of chromatin may reduce transcription and alter the ability of neurons to generate sufficient levels of gene products to maintain normal neocortical function.

Aged↗
PubMedDate not supplied

Functional alterations in neural circuits in Alzheimer's disease.

While a correlation exists at the regional level between the distribution of neurofibrillary tangles and the predicted sites of brain dysfunction based on clinical and functional neuroimaging studies, the relationship between neurofibrillary tangles and neuronal dysfunction is poorly understood. Using cytochrome oxidase activity as a marker of neuronal functional activity, we found reductions in metabolic activity both in a hippocampal subfield with a high density of neurofibrillary tangles (CA1) as well as in subfields relatively spared (CA3, dentate granule cells). In contrast, we found no reduction in activity in primary visual cortex. Using in situ hybridization, we found a selective reduction in a mitochondrial-encoded cytochrome oxidase mRNA transcript with sparing of a nuclear-encoded transcript. These results suggest that the reduction in cytochrome oxidase activity in Alzheimer's disease brain may be related to an alteration in mitochondrial gene expression. The absence of a direct correlation between structural pathology and cytochrome oxidase activity suggests that neurons that remain structurally intact in Alzheimer's disease may nonetheless undergo substantial changes in metabolic activity.

Aged↗
PubMed1997

Neuronal codes: reading them and learning how their structure influences network organization.

Our investigations of the primate visual system show that neuronal responses carry information in a multi-dimensional code that is superimposed onto the response envelope in a slow time varying fashion. The precision of timing is 30 ms or more. In primary visual cortex response latency and response strength are largely independent, with latency more closely coding contrast or visibility and strength more closely coding stimulus orientation, or perhaps shape. Adjacent neurons in both V1 and inferior temporal cortex share only about 10% of their stimulus-related information, which we demonstrate to be consistent with the idea that cortical layers were organized to minimize information loss.

Animals↗
PubMed1995

Crossed quadrant homonymous hemianopsia in a case of multiple sclerosis.

We describe the first report of crossed quadrant hemianopsia (CQHH) occurring in a patient with a well documented clinical history of Multiple Sclerosis (MS). The visual field studied by a Humphrey Field Analyzer (Mod.630, 30-2 program) showed a CQHH, involving right superior quadrants and left inferior ones. Magnetic resonance imaging (MRI) showed two lesions located in both left and right trigone area, corresponding to the geniculocalcarine pathways. CQHH is a very rare visual field defect commonly caused by vertebro-basilar ischemia and attributed to bilateral injury of the calcarine fissure. In the absence of lesions in the primary visual cortex, a direct relationship between the quadrantonopic defect and two small demyelinating lesions in posterior periventricular white matter, corresponding to the geniculocalcarine pathways, is implied.

Adult↗
PubMed1991

Metabolic activation of the rat visual system by patterned light and footshock.

Autoradiography with [14C]2-deoxy-D-glucose was used to examine metabolic changes in the visual system of hooded rats exposed to patterned light or to darkness following footshock. Primary retinorecipient structures (superficial layer of the superior colliculus and the dorsal lateral geniculate nucleus) showed a response to light but not to shock. Higher visual sites showed two different shock effects. First, in darkness the intermediate grey layer of the superior colliculus was suppressed by the shock. Second, in the lateral posterior nucleus and primary visual cortex, the footshock led to significant enhancement of the metabolic responses to the patterned light. The findings suggest that footshock-induced arousal has significant modulatory effects on the operations of higher visual centers of behaving rats.

Analysis of Variance↗
PubMed1994

Brain activation study by use of positron emission tomography in unanesthetized monkeys.

A system for the measurement of brain activity in conscious monkeys by positron emission tomography (PET) was established in the present study. The signal/noise ratio was maximal around 40 s for data acquisition in the PET scan with 15O-labeled water. When the monkey was stimulated by vibration and subtraction images of the data sets from regional cerebral blood flow (rCBF) changes in paired stimulation and control were superimposed on magnetic resonance images obtained from the same specimens, a somatotopic map corresponding to the sites stimulated was clearly demonstrated. Visual stimulation with a photic stimulator activated the corresponding regions of the primary visual cortex. Comparison of the activated sites and extents under the conscious state with those under anesthesia assured that the study is controllable; there was little unpredictable activation due to unlimited subject movement or to psychological effects.

Animals↗
PubMed1995

Retrograde fluorescent microsphere tracing of retinal and central afferents to the nucleus of the optic tract in pigmented and albino rats.

The pretectal nucleus of the optic tract is involved in optokinetic nystagmus. Albino animals suffer from inverse optokinetic nystagmus, possibly due to a smaller number of ipsilateral projections. Animals with laterally placed eyes have an asymmetric nystagmus, attributed to a presumed lack of binocular cortical input to the nucleus of the optic tract. Moreover, a direct input from the ipsilateral retina is controversial. We investigated the retinal and central afferents to the nucleus of the optic tract in the rat by retrograde tracing using fluorescent latex microspheres. Ipsilaterally projecting retinal ganglion cells were observed in pigmented and also in albino rats. Projections from the visual cortex and primary visual nuclei were demonstrated.

Animals↗
PubMed1983

Projection lines and the ipsilateral retino-geniculate pathway in the hooded rat.

The organization of the hooded rat's dorsal lateral geniculate nucleus was studied with anatomical techniques, with particular regard to the representation of temporal retina and the binocular field. The ipsilateral and contralateral retinal terminal fields were examined in three stereotaxic planes following injections of horseradish peroxidase into the eye. Projections arising from the temporal crescent of the retina were studied with silver staining techniques for anterograde degeneration products. Following discrete retinal lesions there was clear evidence that the temporal retina projects in a topographic fashion both ipsilaterally and contralaterally. The orientation of the lines of projection in the dorsal lateral geniculate nucleus was assessed by retrograde labelling of cells after cortical implants of horseradish peroxidase. Although both the lines of projection and the ipsilateral terminal field extend rostro-caudally in the dorsal lateral geniculate nucleus, their paths are oblique rather than parallel. Their intersection appears to correspond to the representation in this nucleus of conjugate retinal points. This was confirmed by administering horseradish peroxidase by iontophoresis in either the binocular or monocular representation of the primary visual cortex, while one eye received an injection of [3H]proline. Only those cortical injections in the binocular region gave rise to labelled projection lines passing through the autoradiographically-labelled ipsilateral terminal field. The rat's dorsal lateral geniculate nucleus displays none of the cytoarchitectural lamination which is so prominent in the primate and cat. Even after labelling the input to the nucleus from one eye, there is still no obvious laminar relationship between the terminal fields from the two eyes. Despite the absence of lamination, the current results suggest that the principle of apposing the representation of conjugate retinal points in the dorsal lateral geniculate nucleus is the same in the rat as in cat and monkey.

Animals↗
PubMed1990

Organization of cortical afferent and efferent pathways in the white matter of the rat visual system.

Fibers forming reciprocal connections between the dorsal lateral geniculate nucleus and primary visual cortex run in separate tracts in the white matter. The corticofugal fibers are organized into bundles which project through the coronal plane at an oblique angle. We have examined the organization of corticofugal fiber tracts within the white matter of the rat using cortical slices which encompassed the predicted trajectory of these fiber bundles. Field potentials were evoked in layer VI of visual cortex by focal stimulation of subcortical white matter using microbipolar electrodes. Two major responses were elicited: a short-latency and a longer-latency response. The short-latency response was elicited in the superficial strata of white matter with proximal stimulation sites and was obtained in deeper strata for more distant, lateral sites. The longer-latency response was associated with superficial strata in white matter at both proximal and distant stimulation sites. Based on the electrophysiological properties and the white matter location for eliciting these responses, it is likely that the short-latency response is due to antidromic activation of corticogeniculate fibers, whereas the longer-latency response probably arises from orthodromic activation of geniculocortical fibers. These findings provide an electrophysiological demonstration that cortical afferent and efferent pathways are segregated within the white matter and that they can be selectively activated by focal stimulation. The fact that the fiber bundle model successfully predicted the trajectory of corticofugal fibers provides additional support for this model of white matter organization. A double labeling technique which combined orthograde axonal transport and neuronal degeneration was used to examine the topographic arrangement of corticofugal fibers in the white matter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Exogenous supply of nerve growth factor prevents the effects of strabismus in the rat.

It has recently been reported that exogenous supply of nerve growth factor prevents the effects of monocular deprivation both in rats and in cats. Here we have extended these experiments to the case of strabismus. Repeated intraventricular injections of nerve growth factor were performed in rats made surgically strabismic early in the critical period. At the end of the critical period the ocular dominance distribution of visual cortical neurons was assessed in strabismic untreated, strabismic nerve growth factor-treated and strabismic Cytochrome C-treated (control) rats by means of extracellular recordings. We found that in rats surgical strabismus causes a consistent loss of binocular neurons. By contrast the treatment with nerve growth factor maintains the normal ocular dominance distribution of neurons in the primary visual cortex. We conclude that nerve growth factor exogenously supplied prevents the effects induced by surgical strabismus in rats and suggest that nerve growth factor has a role in visual cortical plasticity.

Animals↗
PubMed1993

Laminar organization of acetylcholinesterase and cytochrome oxidase in the lateral geniculate nucleus of prosimians.

Hess and Rockland [Hess and Rockland (1983) Brain Res. 289, 322-325] proposed that the distribution of acetylcholinesterase within the lateral geniculate nucleus might correlate with the daily activity patterns shown by primates. In diurnal primates, the magnocellular laminae show a greater acetylcholinesterase reaction product. In nocturnal primates, the parvocellular laminae are more heavily stained. We have examined the laminar distribution of acetylcholinesterase and cytochrome oxidase in the lateral geniculate nucleus of a series of rare prosimian primates. In all prosimians examined, the most dense acetylcholinesterase reaction product is seen in the parvocellular layers of the lateral geniculate nucleus. Heavy cytochrome oxidase activity is seen in both the magnocellular and parvocellular layers, but not the koniocellular layers of the prosimian lateral geniculate nucleus. We have also employed a polyclonal antibody to choline acetyltransferase to examine the laminar organization or cholinergic activity in the Galago (Bushbaby) lateral geniculate nucleus. We report that choline acetyltransferase immunoreactivity does not correlate with acetylcholinesterase activity in the prosimian lateral geniculate nucleus. Although the lateral geniculate nucleus is more immunoreactive than most other thalamic structures and although the intercalated koniocellular laminae demonstrate somewhat lighter choline acetyltransferase immunoreactivity, no great difference in staining intensity is seen between the parvocellular and magnocellular laminae. In addition, we examined the phenotype of known inputs to assess the laminar specificity of cholinergic projections to the bushbaby lateral geniculate nucleus. Layer VI of primary visual cortex, which is known to be a source of acetylcholinesterase in the parvocellular layers, does not contain cholinergic cells, nor does the pretectal nucleus, which projects mainly to the parvocellular layers. The parabigeminal nucleus is cholinergic; however, this nucleus is known to project to the koniocellular layers, along with the non-cholinergic superior colliculus. Finally, the pedunculopontine tegmental nucleus, which provides a strong input to many regions of the thalamus, including the lateral geniculate nucleus, is cholinergic. The laminar organization of its input to the lateral geniculate nucleus is not known. Increased acetylcholinesterase reaction product within the parvocellular layers of the lateral geniculate nucleus is common to all strepsirhine primates. The pattern is also seen in the only two nocturnal haplorhine primates, Tarsius and Aotus (owl monkey). The relation of this increased acetylcholinesterase activity to cholinergic function remains unclear.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗
PubMed1995

Disproportionate regulation of nuclear- and mitochondrial-encoded cytochrome oxidase subunit proteins by functional activity in neurons.

Cytochrome oxidase is the terminal enzyme in the mitochondrial respiratory chain engaged in oxidative metabolism and energy production. In mammals, the holoenzyme is composed of 13 subunits encoded by both nuclear and mitochondrial genomes. The goal of the present study was to compare the effect of afferent impulse blockade on the expression of these two genomes at the subunit protein level. It also aimed to determine the correlation between the level of cytochrome oxidase activity and the relative amount of subunit proteins. Relative enzyme activity was analysed histochemically, and relative amounts of subunits IV (nuclear-encoded) and II/III (mitochondrial-derived) proteins were obtained immunohistochemically by anti-subunit IV and anti-subunit II/III antibodies in the lateral geniculate nucleus and the primary visual cortex of adult monkeys. In the normal visual centers, similar staining patterns were found for all three markers. After three and seven days of tetrodotoxin treatment, levels of enzyme activity and subunit proteins declined disproportionately in the deprived laminae of the visual center. Densitometric analysis indicates that changes in enzyme activity and subunit IV proteins were significantly greater than those of subunit II/III proteins (P < 0.01). The finding that nuclear and mitochondrial genomes are disproportionately regulated at subunit protein levels by neuronal activity implies that the two genomes operate under different regulatory mechanisms. Changes in subunit IV paralleled most closely those of cytochrome oxidase activity (coefficient of determination r2 = 0.95). This suggests that nuclear-derived subunit IV protein may play a pivotal role in controlling cytochrome oxidase holoenzyme activity.

Animals↗
PubMedDate not supplied

Recovery of function after brain damage: the extrinsic stimulus specificity of spared neural traces.

Previous research has demonstrated that while primary visual cortex lesions in rats will disrupt performance of a learned brightness discrimination, the neural traces associated with this discrimination are spared. Moreover, the spared neural traces may, in certain instances, influence the postoperative reinstatement of a brightness discrimination. The present research was designed to determine the generality of this postoperative influence. The results indicate that while the normal rat and the visual decorticate rat may readily transfer learning between discriminations involving different discriminative cues, a visual lesion between two discriminations prevents this transfer. These data are interpreted as indicating that the postoperative influence of a spared neural trace is dependent upon the reoccurrence of specific extrinsic stimulus cues.

Animals↗
PubMed1995

Distribution of dopaminergic fibers and neurons in visual and auditory cortices of the harbor porpoise and pilot whale.

The distribution of putative dopaminergic fibers in two sensory cortical areas in the brain of the harbor porpoise (Phocoena phocoena) and pilot whale (Globicephala melaena) was analyzed at the light and electron microscopic levels using tyrosine hydroxylase (TH) immunohistochemistry. The quantitative analysis of the distribution of labeled fibers demonstrates that the primary visual cortex located in the lateral gyrus and entolateral sulcus contains a denser dopaminergic innervation than the auditory cortex within the posterior portion of the presylvian gyrus. In both areas, TH-immunoreactive fibers are densest in layer I, while layers IIIab and VI have intermediate densities and layers II and IIIc-V have the lowest fiber counts. Layer I is characterized by the presence of very thick TH-immunoreactive fiber populations, in addition to the thin and varicose fiber plexus observed throughout the cortical layers. Electron microscopic analyses demonstrated that some of these thick fibers represent the dendrites of TH-immunoreactive neurons located in the deep portion of layer I. The patterns observed in the present study suggest that the dopaminergic projections to the neocortex in whales have a different organization than in terrestrial mammals, particularly rodents and primates. These differences may reflect the fact that during evolution, the cetacean neocortex has retained many of the cytoarchitectonic features that are usually observed only in proisocortical regions in progressive terrestrial mammals.

Animals↗
PubMed1995

Localization of the two protein kinase C beta-mRNA subtypes in cat visual system.

Protein kinase C (PKC) consists of a family of different subtypes encoded by different PKC genes. We investigated the distribution of PKC beta 1 and PKC beta 2 in the visual system of the adult cat by in situ hybridization using oligonucleotide probes complementary to the PKC beta 1 and PKC beta 2 mRNAs, two splicing variants of the same gene transcript. In the primary visual cortex PKC beta 1 and PKC beta 2 were both present. The laminar distribution patterns found for the two PKC subtypes were identical. A remarkable finding was the difference between the laminar distribution of the PKC beta s in areas 17 and 18 when compared with area 19. In all three areas the highest expression levels were found in layer VI, moderately high levels were found in layers II, III and V, while layer I was devoid of signal. In area 17 and 18 layer IV stood out by its low PKC beta signal. In sharp contrast, layer IV of area 19 was indiscernible from the superficial layers because of an evenly high signal. In the dLGN of the adult cat PKC beta 1 and PKC beta 2 mRNAs were distributed rather homogeneously over the different layers, but the expression levels for PKC beta 1 were clearly higher than those for PKC beta 2.

Animals↗
PubMed1991

Differential expression of voltage-gated calcium channels in identified visual cortical neurons.

Using the whole-cell patch-clamp technique, Ca2+ channel currents were examined in three distinct types of neurons derived from rat primary visual cortex. Callosal-projecting and superior colliculus-projecting neurons were identified following in vivo retrograde labeling with fluorescent "beads." A subset of intrinsic GABAergic visual cortical neurons was identified with the monoclonal antibody VC1.1. Although high voltage-activated Ca2+ channel currents were measured in all three cell types, clear differences in the densities of these channels were observed. There were also marked variations in the relative amplitudes of the inactivating and noninactivating components of the high voltage-activated currents, suggesting that N- and L-type Ca2+ channels are differentially distributed. Although low voltage-activated or T-type currents were measured in subsets of both types of projection neurons, they were not observed in VC1.1-positive cells. These results provide a direct demonstration that voltage-gated Ca2+ channels are expressed in neurons of the mammalian visual cortex and reveal that the distribution and densities of different Ca2+ channel types in diverse classes of visual cortical neurons are distinct.

Animals↗
PubMed1995

Improvement in visual sensitivity by changes in local context: parallel studies in human observers and in V1 of alert monkeys.

To explore the role of primary visual cortex in contour integration, we measured the contextual sensitivity of human contrast thresholds and of superficial layer complex cells in monkey V1. An observer's contrast detection was 40% improved by a second suprathreshold bar; the effect was decreased as the two bars were separated along their axis of orientation, were displaced from colinearity, and had their relative orientation changed. Recordings from V1 showed that 42% of complex cells demonstrated facilitation for a second bar outside their classical receptive fields with a similar dependency on relative location and orientation. Both effects were eliminated by an orthogonal line between the two iso-oriented lines. Multiple randomly placed and oriented lines in the receptive field surround often caused a reduction in a cell's response to an optimally oriented stimulus, but this inhibition could be eliminated by changing the orientation of a few of these elements to colinearity with the centrally located target.

Animals↗
PubMed1995

Parallel versus serial processing: new vistas on the distributed organization of the visual system.

Recent functional studies question the validity of the hierarchical model of organization for processing visual information in cortical areas. The results of these studies suggest that beyond the primary visual cortex (V1), information is not serially processed through successive cortical areas, but that it is simultaneously processed in several areas. The idea that visual information is functionally segregated into different, parallel channels as it circulates through V1 and V2 towards V4 and the middle temporal visual area is also challenged by recent studies that report a smaller degree of functional specialization within the visual areas than previously thought.

Animals↗