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Biomedical subjects

C Blakemore

Publications and source records attributed to C Blakemore.

172 records · Page 10Linked to original sources

The neural mechanism of binocular depth discrimination.

1. Binocularly driven units were investigated in the cat's primary visual cortex.2. It was found that a stimulus located correctly in the visual fields of both eyes was more effective in driving the units than a monocular stimulus, and much more effective than a binocular stimulus which was correctly positioned in only one eye: the response to the correctly located image in one eye is vetoed if the image is incorrectly located in the other eye.3. The vertical and horizontal disparities of the paired retinal images that yielded the maximum response were measured in 87 units from seven cats: the range of horizontal disparities was 6.6 degrees , of vertical disparities 2.2 degrees .4. With fixed convergence, different units will be optimally excited by objects lying at different distances. This may be the basic mechanism underlying depth discrimination in the cat.

Action Potentials↗

Phospholipase C-beta1 expression correlates with neuronal differentiation and synaptic plasticity in rat somatosensory cortex.

Receptor-mediated signal transduction is thought to play an important role in neuronal differentiation and the modification of synaptic connections during brain development. The intracellular signalling molecule phospholipase C-beta1 (PLC-beta1), which is activated via specific neurotransmitter receptors, has recently been implicated in activity-dependent plasticity in the cat visual cortex. PLC-beta1 has been shown to be concentrated in an intermediate compartment-like organelle, the botrysome, which is present in 5-week-old, but not adult, cat cortical neurons. We have characterized the spatial and temporal regulation of PLC-beta1 expression in the developing rat cerebral cortex. PLC-beta1-positive botrysome-like organelles are observed during early postnatal cortical development, but not at postnatal day 14 or later stages. In the postnatal somatosensory cortex, there is also striking spatial variation in diffuse neuropilar immunoreactivity of layer IV and above, in a pattern corresponding to the thalamocortical recipient zones known as barrels. This expression pattern is specific to the developing barrel field and is most distinct at postnatal days 4-7, when cellular components of barrels are capable of activity-dependent modification. During later stages of cortical maturation, stained botrysomes disappear, expression of PLC-beta1 is down-regulated and only diffuse immunoreactivity remains in dendritic processes. Our results are consistent with a role for PLC-beta1 in activity-dependent, receptor-mediated neuronal plasticity during development of the somatosensory cortex.

Animals↗

Anterior cingulate cortical transplantation in transgenic Huntington's disease mice.

Huntington's disease (HD) is an autosomal dominant disorder involving progressive neurodegeneration of the corpus striatum and cerebral cortex. Transgenic mice, in which exon 1 of the human HD gene with an expanded trinucleotide repeat is expressed, develop a neurodegenerative syndrome that closely models human HD. Transplantation of wild-type donor cortex into the anterior cingulate cortex of neonatal HD mice (R6/1 line) was found to delay the onset of a specific motor deficit, rear-paw clasping. However, transplantation did not significantly enhance motor performance on a suspended horizontal rod, a behavioural measure of fine motor co-ordination. Control experiments in which the anterior cingulate cortex was resected, but no donor cortical tissue was transplanted, showed no behavioural benefit. In fact, wild-type littermate mice that also underwent this surgical resection, were found to develop motor deficits similar to those exhibited by non-resected HD mice. These results suggest that the anterior cingulate cortex is an important area of pathology in this HD model, and that therapeutic approaches to HD may need to target cortical, as well as striatal areas.

Animals↗

Functional architecture of area 17 in normal and monocularly deprived marmosets (Callithrix jacchus).

The organization of the primary visual cortex (VI) of the common marmoset (Callithrix jacchus) was studied both physiologically and by means of transneuronal labelling of geniculocortical afferents. We addressed the question whether monocular deprivation (MD) could stabilize segregation into ocular dominance (OD) columns, which are not seen in normal adult marmosets but are present in juvenile animals (Spatz, 1979, 1989). Properties of neurons in normal marmosets closely resembled those of other New-World and Old-World monkeys and orderly tangential progressions of preferred orientation were observed. However, in contrast to species that display well-defined OD columns, neurons of layer 4 in V1 of normal adult marmosets received balanced inputs from the two eyes. Early MD (even though followed by prolonged binocular experience into adulthood) resulted in a reduction of cell size in laminae of the lateral geniculate nucleus with input from the deprived eye and a dramatic overall shift in ocular dominance towards the nondeprived eye in the cortex. However, isolated clusters of cells dominated by the deprived eye were found in both layers 4 and 6. Injection of lectin-conjugated horseradish peroxidase (WGA-HRP) into the deprived eye revealed elongated patches of terminal label, about 350 microns wide, in flat-mounted sections through layer 4. Afferent segregation was sharper and more regular in the region of V1 representing parafoveal visual space than in that representing the fovea. Our findings support the notion that all Old-World and New-World monkeys possess the capacity for segregation of geniculocortical afferents into OD columns.

Afferent Pathways↗

Ganglion cell death during development of ipsilateral retino-collicular projection in golden hamster.

In rats and hamsters all parts of the superior colliculus (SC) receive a topographically organized projection from the retina of the contralateral eye, and the rostral part also has a direct input from the lower temporal crescent of the ipsilateral retina, which views the central, binocular portion of the visual field. Initially the uncrossed projection covers the entire SC, but over the first 2 weeks of postnatal life it becomes progressively restricted to its adult distribution. However, if the opposite eye is removed at birth there is a persistent widespread uncrossed projection to the SC. We have used short- and long-term retrogradely transported neuronal markers to examine the distribution and fate of the ganglion cells of origin of the uncrossed retino-collicular projection throughout postnatal development. We conclude that the withdrawal of the early exuberant projection to the caudal SC is associated with death of ganglion cells and their virtual elimination outside the temporal crescent of the ipsilateral retina. Early enucleation of the other eye rescues many of these cells.

Animals↗

Regressive events in the postnatal development of association projections in the visual cortex.

In newborn kittens, neurones in area 17 of the visual cortex projecting to area 18 are distributed in bands of uniform density across the superficial layers (laminae II, III and the upper part of IV) and the deep layers (V and VI). During weeks 2 and 3 postnatal, the cells of origin of this association pathway become mainly restricted to discrete, dense clusters, approximately 600 microns from centre to centre, in the upper layers, with intervening zones free of association cells, as in the adult cat. We have used retrogradely transported, long-lasting neuronal markers to investigate this developmental refinement of the pattern of cortico-cortical connections. The results, reported here, indicate that axonal retraction plays a significant part in the maturation of the clustered organization of superficial layer neurones projecting to area 18, but that cell death may also be a factor in the elimination of the inappropriate projection from the deep laminae.

Amidines↗

Identification of proteins downregulated during the postnatal development of the cat visual cortex.

To identify proteins that play a role in the development of the mammalian visual cortex, we have used an immunosuppression and rapid immunization strategy to generate monoclonal antibodies to antigens that are present in area 17 of the cat during the peak of cortical plasticity but are downregulated near the end of the plastic period. We report here the immunohistochemical and immunobiochemical characterization of six monoclonal antibodies that identify antigens preferentially expressed in the cat visual cortex at 5 weeks of age. Monoclonal antibodies Cat-305 and Cat-306 detect three immunoreactive elements that are not present at birth but are present at 5 weeks. The majority of immunoreactivity is associated with a population of cells in the white matter that are absent at 15 weeks of age. At both 5 and 15 weeks, a very small number of neurons show intense immunoreactivity throughout all processes, resembling that achieved with a Golgi stain. In addition, a diffuse band of immunoreactivity in layer IV is largely restricted to cortical areas 17 and 18. Cat-307 recognizes a 150 kDa soluble protein present in small cytoplasmic inclusions. These cytoplasmic "dot" are present in all layers, but are most prominent in layer V. Cat-307 immunoreactivity is present at birth and is completely downregulated by 15 weeks. Cat-104 and Cat-105 recognize a 200 kDa insoluble protein present at birth and at 5 weeks, but markedly downregulated by 15 weeks. At birth, the white matter, subplate, and layer I are most densely labeled, while at 5 weeks labeling is densest in layers II, III, and V. Cat-402 recognizes a number of high-molecular-weight antigens that are differentially expressed at 5 and 15 weeks of age. Stained non-neuronal cells that resemble protoplasmic astrocytes are present in all layers at both 5 and 15 weeks. At 5 weeks, but not at birth or 15 weeks, darkly immunoreactive radial processes are observed that run through the full depth of the cortex. We show here that immunoreactivity for several different monoclonal antibodies is detected selectively during the period of maximal developmental plasticity. The results demonstrate that the cat visual cortex at 5 weeks of age is molecularly distinct from the cortex at 15 weeks.

Animals↗

Analysis of connectivity: neural systems in the cerebral cortex.

The mammalian cerebral cortex is composed of many distinct areas, which are very richly interconnected. The very large number of connections between cortical areas require analysis to be undertaken before reliable conclusions about the organization of neural systems in the cortex can be drawn. We review the methodology and results of two means of analysing central nervous connectivity, hierarchical analysis and optimization analysis. We conclude that these methods are reliable methods for analysing neural connectivity data, and that their results concur. The analyses indicate that all major cortical sensory systems are organized hierarchically, some central sensory systems are divided structurally into several "streams" of processing, the cortical motor system is embedded in the cortical somatosensory system, the frontal and limbic structures are connectionally associated, and that these frontal and limbic areas are invariably associated with the least peripheral sensory processing regions, and are therefore connectionally central. Finally, we discuss the differences on this common plan between the organizations of the cat and primate that these analyses reveal.

Animals↗