Search PubMed⌕ Search

Biomedical subjects

C Blakemore

Publications and source records attributed to C Blakemore.

At least 37 records · Page 2Linked to original sources

Phospholipase C-beta1 is present in the botrysome, an intermediate compartment-like organelle, and Is regulated by visual experience in cat visual cortex.

Monoclonal antibody Cat-307 identifies a 165 kDa neuronal protein expressed in the cat visual cortex during the period of sensitivity to alterations in visual experience (). Dark-rearing, which prolongs the sensitive period, also prolongs the expression of the Cat-307 protein. The Cat-307 protein localizes to an organelle, here called the botrysome (from the Greek botrys, cluster of grapes), that is located between the endoplasmic reticulum (ER) and Golgi apparatus. The botrysome is composed of small ring-shaped profiles with electron-dense coats. The size and morphology of the rings and their coats are similar to those described for ER to Golgi transport vesicles. Biochemically, the Cat-307 protein cofractionates with microsomes and partitions with subunits of the coatomer proteins that coat ER-to-Golgi transport vesicles. Partial amino acid sequencing reveals that the Cat-307 protein is phospholipase C-beta1, the G-protein-dependent phosphodiesterase that hydrolyses phosphatidylinositol 4,5 biphosphate into inositol 1,4,5 triphosphate and diacylglycerol after the stimulation of a variety of neurotransmitter receptors at the cell surface. These results suggest a role for phospholipase C-beta1 and the botrysome in developmental plasticity and provide a possible link between receptor activation at the cell surface and protein transport during neuronal development.

Animal Husbandry↗

Development of contrast sensitivity and temporal-frequency selectivity in primate lateral geniculate nucleus.

We studied the development of spatial contrast-sensitivity and temporal-frequency selectivity for neurons in the monkey lateral geniculate nucleus. During postnatal week 1, the spatial properties of P-cells and M-cells are hardly distinguishable, with low contrast-sensitivity, sluggish responses, and poor spatial resolution. The acuity of P-cells improves progressively until at least 8 months, but there is no obvious increase in their maximum contrast-sensitivity with age. The contrast sensitivity of M-cells is already clearly higher than that of P-cells by 2 months, and at 8 months of age this characteristic difference between M- and P-cells approaches the adult pattern. There is a major increase in responsiveness during the first 2 postnatal months, especially for M-cells, the peak firing rate of which rises fivefold, on average, between birth and 2 months. Many P-cells in the neonatal and 2-month-old animals did not give statistically reliable responses to achromatic gratings, even at the highest contrasts: this unresponsiveness of P-cells might result from low gain and/or chromatic opponency. The upper limit of temporal resolution in the neonate is low--about one-third of that in the adult. Among M-cells, the improvement in temporal resolution, like that in contrast sensitivity, is rapid over the first 2 months, followed by a slower change approaching the adult value by 8 months of age. The development of contrast sensitivity, responsiveness and temporal tuning are little affected, if at all, by binocular deprivation of pattern vision from birth for even a prolonged period.

Aging↗

Characteristics of surround inhibition in cat area 17.

The effects of stimuli falling outside the 'classical receptive field' and their influence on the orientation selectivity of cells in the cat primary visual cortex are still matters of debate. Here we examine the variety of effects of such peripheral stimuli on responses to stimuli limited to the receptive field. We first determined the extent of the classical receptive field by increasing the diameter of a circular patch of drifting grating until the response saturated or reached a maximum, and by decreasing the diameter of a circular mask in the middle of an extended grating, centred on the receptive field, until the cell just began to respond. These two estimates always agreed closely. We then presented an optimum grating of medium-to-high contrast filling the classical receptive field while stimulating the surround with a drifting grating that had the same parameters as the central stimulus but was varied in orientation. For all but five neurons (of 37 tested), surround stimulation produced clear suppression over some range of orientations, while none showed explicit facilitation under these conditions. For 11 cells (34% of those showing suppression), the magnitude of suppression did not vary consistently with the orientation of the surround stimulus. In the majority of cells, suppression was weakest for a surround grating oriented orthogonal to the cell's optimum. Nine of these cells (28%) exhibited maximum inhibition at the optimum orientation for the receptive field itself, but for 12 cells (38%) there was apparent 'release' from inhibition for surround gratings at or near the cell's optimum orientation and direction, leaving inhibition either maximal at angles flanking the optimum (9 cells) or broadly distributed over the rest of the orientation range (3 cells). This implies the existence of a subliminal facilitatory mechanism, tightly tuned at or near the cell's optimum orientation, extending outside the classical receptive field. For just two cells of 13 tested the preferred orientation for a central grating was clearly shifted towards the orientation of a surrounding grating tilted away from the cell's optimum. The contrast gain for central stimulation at the optimal orientation was measured with and without a surround pattern. For nine of 25 cells tested, surround stimulation at the cell's optimum orientation facilitated the response to a central grating of low contrast (< or =0.1) but inhibited that to a higher-contrast central stimulus: the contrast-response gain is reduced but the threshold contrast is actually decreased by surround stimulation. Hence the receptive field is effectively larger for low-contrast than for high-contrast stimuli. Inhibition from the periphery is usually greatest at or around the cell's optimum, while suppression within the receptive field has been shown to be largely non-selective for orientation. Inhibition by orientations flanking the optimum could serve to sharpen orientation selectivity in the presence of contextual stimuli and to enhance orientational contrast; and it may play a part in orientation contrast illusions.

Animals↗

Is the motion system relatively spared in amblyopia? Evidence from cortical evoked responses.

Visual evoked potentials (VEPs) produced by pattern reversal were compared with those elicited by onset of motion in 37 amblyopic children (20 with anisometropic amblyopia, seven with strabismic amblyopia and 10 with both anisometropia and strabismus). The amplitudes and peak latencies of the main P1 peak in the pattern-reversal VEP and of the motion-specific N2 peak in the motion-onset VEP through the amblyopic eye were compared with those through the normal fellow eye. Regardless of the type of amblyopia, the amplitude of the pattern-reversal VEP for full-field stimulation was significantly smaller and its latency significantly longer through the amblyopic eye (P < 0.001). In contrast, neither the amplitudes nor the latencies of the N2 motion-onset VEPs differed significantly between amblyopic and non-amblyopic eyes. For pattern-reversal VEPs through the amblyopic eyes, the extent to which amplitude was reduced and latency prolonged correlated well with the reduction of visual acuity, whereas the amplitudes and latencies of motion-onset VEPs did not vary with visual acuity. Even for stimuli restricted to the central visual field (5 or 2 deg diameter) or to the peripheral field (excluding the central 5 deg), motion-onset responses were indistinguishable through the two eyes, while pattern-reversal responses always differed significantly in amplitude. These results suggest that the source of motion-onset VEPs (probably an extrastriate motion-sensitive area) is less affected in amblyopia than that of pattern-reversal VEPs (probably the striate cortex). The motion pathway, presumably deriving mainly from the magnocellular layers of the lateral geniculate nucleus, may be relatively spared in amblyopia.

Adolescent↗

The neural basis of suppression and amblyopia in strabismus.

The neurophysiological consequences of artificial strabismus in cats and monkeys have been studied for 30 years. However, until very recently no clear picture has emerged of neural deficits that might account for the powerful interocular suppression that strabismic humans experience, nor for the severe amblyopia that is often associated with convergent strabismus. Here we review the effects of squint on the integrative capacities of the primary visual cortex and propose a hypothesis about the relationship between suppression and amblyopia. Most neurons in the visual cortex of normal cats and monkeys can be excited through either eye and show strong facilitation during binocular stimulation with contours of similar orientation in the two eyes. But in strabismic animals, cortical neurons tend to fall into two populations of monocularly excitable cells and exhibit suppressive binocular interactions that share key properties with perceptual suppression in strabismic humans. Such interocular suppression, if prolonged and asymmetric (with input from the squinting eye habitually suppressed by that from the fixating eye), might lead to neural defects in the representation of the deviating eye and hence to amblyopia.

Amblyopia↗

Testing for Passovoy defect in children with prolonged activated partial thromboplastin time (APTT)

PURPOSE: To investigate the value of testing for Passovoy defect using the commercially available Passovoy trait plasma (PTP) in children with prolonged activated partial thromboplastin time (APTT). PATIENTS AND METHODS: We studied 13 children with prolonged APTT that corrected in a 1:1 mix with normal human plasma but not with PTP. In most children, a thorough laboratory investigation of the intrinsic pathway factors and von Willebrand factor was performed. RESULTS: Five patients had bleeding manifestations and eight were asymptomatic. Measurement of von Willebrand factor and intrinsic pathway factors revealed abnormal values in eight patients (low von Willebrand activity in six patients, low factor XII in one patient, and the presence of lupus anticoagulant in one patient). CONCLUSION: Our data suggest inability to diagnose Passovoy defect based on a mixing study. This study also raises the question of whether Passovoy defect exists as a distinct coagulation disorder.

Adolescent↗

Visual motion processing in the anterior ectosylvian sulcus of the cat.

1. Neurons that are selectively sensitive to the direction of motion of elongated contours have been found in several cortical areas in many species. However, in the striate cortex of the cat and monkey, and the extrastriate posteromedial lateral suprasylvian visual area of the cat, such cells are generally component motion selective, signaling only the direction of movement orthogonal to the preferred orientation; a direction that is not necessarily the same as the motion of the entire pattern or texture of which the cell's preferred contour is part. The primate extrastriate middle temporal area is the only cortical region currently known to contain a substantial population of pattern-motion-selective cells that respond to the shared vector of motion of mixtures of contours. 2. From analyzing published data on the connectivity of the cat's cortex, we predicted that the anterior ectosylvian visual area (AEV), situated within the anterior ectosylvian sulcus, might be a higher-order motion processing area and thus likely to contain pattern-motion-selective neurons. This paper presents the results of a study on neuronal responses in AEV. 3. Ninety percent of AEV cells that responded strongly to drifting grating and/or plaid stimuli were directionally selective (directionality index > 0.5). For this group, the mean directionality index was 0.75. Moreover, 55% of these cells were unequivocally classified as pattern motion selective and only one neuron was classified as definitely component motion selective. Thus high-level pattern motion coding occurs in the cat extrastriate cortex and is not limited to the primate middle temporal area. 4. AEV contains a heterogeneous population of directionally selective cells. There was no clear relation between the degree of directional selectivity for plaids or gratings and the degree of selectivity for pattern motion or component motion. Nevertheless, 28% of the highly responsive cells were both more strongly modulated by plaids than gratings and more pattern motion selective than component motion selective. Such cells could correspond to a population of "selection units" signaling the salience of local motion information. 5. AEV lacks global retinotopic order but the preferred direction of motion of neurons (rather than axis of motion, as in the middle temporal area and the posteromedial lateral suprasylvian visual area) is mapped systematically across the cortex. Our data are compatible with AEV being a nonretinotopic, feature-mapped area in which cells representing similar parts of "motion space" are brought together on the cortical sheet.

Animals↗

Early history of IBRO: the birth of organized neuroscience.

To celebrate the thirtieth anniversary of the founding of the International Brain Research Organization (IBRO), a symposium was organized for the III Congress of the World Federation of Neuroscientists in Montreal to present, on 7 August 1991, the recollections of some of the early participants in IBRO's history and to place it in the context of other significant world organizations. Edited and slightly condensed transcripts of the talks together with the discussions are presented. L. Marshall reviewed the antecedent conferences that led to the Moscow Colloquium in 1958 and the subsequent formation of IBRO with UNESCO support. The ambience of that period for scientific organization on an international level was discussed by W. A. Rosenblith who emphasized how IBRO goals fitted into the rising interest in brain and behavior research. The scientific careers of six past executive secretaries were briefly reviewed by P. Gloor, with special tribute to the first, Herbert Jasper. One of IBRO's major achievements, the world survey of resources and needs in brain research, was described first-hand by G. Krauthamer. To discuss IBRO's image, C. Blakemore invoked the travails of reorganization and recovery from a period of inactivity. Finally, placing IBRO in a national and international context, S. Cozzens presented the perspective of the historian of sociology on an upbeat note.

History, 20th Century↗

Interocular suppression in cat striate cortex is not orientation selective.

For the majority of neurones in cat striate cortex, the response to an optimal stimulus presented to one eye is suppressed when a stimulus of substantially different orientation is presented to the other eye. In order to determine the true orientational tuning of the underlying inhibitory interactions in the absence of binocular facilitation for matched stimuli, we tested how the response of such cells to an optimal grating in one eye is affected by gratings in the other eye of spatial frequencies too high or low to elicit an excitatory response through either eye: the vast majority of cells displayed suppression that was essentially independent of orientation. Our results indicate that interocular inhibition derives from cells representing all orientations, but is swamped by interocular facilitation for stimuli matched in orientation and spatial frequency.

Animals↗

Non-metric multidimensional scaling in the analysis of neuroanatomical connection data and the organization of the primate cortical visual system.

Neuroanatomists have established that the various gross structures of the brain are divided into a large number of different processing regions and have catalogued a large number of connections between these regions. The connectional data derived from neuroanatomical studies are complex, and reliable conclusions about the organization of brain systems cannot be drawn from considering them without some supporting analysis. Recognition of this problem has recently led to the application of a variety of techniques to the analysis of connection data. One of the techniques that we previously employed, non-metric multidimensional scaling (NMDS), appears to have revealed important aspects of the organization of the central nervous system, such as the gross organization of the whole cortical network in two species. We present here a detailed treatment of methodological aspects of the application of NMDS to connection data. We first examine in detail the particular properties of neuroanatomical connection data. Second, we consider the details of NMDS and discuss the propriety of different possible NMDS approaches. Third, we present results of the analyses of connection data from the primate visual system, and discuss their interpretation. Fourth, we study independent analyses of the organization of the visual system, and examine the relation between the results of these analyses and those from NMDS. Fifth, we investigate quantitatively the performance of a number of data transformation and conditioning procedures, as well as tied and untied NMDS analysis of untransformed low-level data, to determine how well NMDS can recover known metric parameters from artificial data. We then re-analyse real connectivity data with the most successful methods at removing the effects of sparsity, to ensure that this aspect of data structure does not obscure others. Finally, we summarize the evidence on the connectional organization of the primate visual system, and discuss the reliability of NMDS analyses of neuroanatomical connection data.

Animals↗

Guidance of thalamocortical innervation.

We propose that a sequence of individually simple mechanisms influences the pattern of thalamocortical innervation, which itself contributes to the determination of regional differentiation of the neocortex. In co-culture, the cortex appears to exert a remote growth-promoting influence on thalamic axons from E15, becomes growth-permissive to axon invasion at about E20 and expresses a stop signal, causing termination in layer IV, from P2-3. This cascade of cortical signals may determine the timing of events in vivo. However, any part of the thalamus will innervate any region of the developing cortex in culture, without obvious preference, suggesting that the topographic distribution of thalamic fibres in vivo does not depend on regional chemospecificity. The initial extension of axons from the cortical preplate and the thalamus starts at about E14, and the topography of both may be influenced by their temporal sequences of outgrowth (chronotopy). The axon arrays meet in the basal telencephalon, after which the preplate scaffold may guide thalamic axons and ensure both their 'capture' within the subplate layer and the establishment of the waiting period. The unusual pattern of innervation in the Reeler mutant mouse supports the hypothesis that thalamic axons grow over preplate fibres to find the waiting compartment.

Animals↗

Interocular suppression in the primary visual cortex: a possible neural basis of binocular rivalry.

In an attempt to demonstrate a physiological basis for the alternating suppression of perception when the two eyes view very different contours (binocular rivalry), we studied the responses of neurons in the lateral geniculate nucleus (LGN) and area 17 of cats for drifting gratings of different orientation, spatial frequency and contrast in the two eyes. Almost half of the LGN neurons studied exhibited modest inhibitory interocular interaction, but independent of interocular differences in orientation. Monocularly driven units in layer 4 of area 17 behaved similarly. However, for the majority of binocular cortical cells, the response to a grating of optimal orientation in one eye was suppressed by a grating of very different orientation shown to the other eye, over a wide range of spatial frequency and independent of relative spatial phase. This interocular suppression exhibits a remarkable non-linearity: a grating of non-preferred orientation in one eye causes significant interocular suppression only if the neuron is already responding to an appropriate stimulus in the other eye [Sengpiel and Blakemore (1994) Nature, 368, 847-850]. We propose that the switches in perceptual dominance during binocular rivalry depend on interocular interactions at the level of binocular neurons of the primary visual cortex, which might involve intracortical inhibition between adjacent ocular dominance columns. The spontaneous alternations in perceptual suppression that occur during prolonged viewing of rivalrous patterns remain to be explained, although significant variation in the strength of neuronal suppression in such conditions was occasionally seen.

Action Potentials↗

Contrast dependence of motion-onset and pattern-reversal evoked potentials.

This study deals with the effect of stimulus contrast, between 1.3% and 96%, on the visual evoked potentials (VEPs) for onset of motion and for pattern reversal of checkerboard stimuli. The VEPs for pattern reversal and for the onset of motion both contain an initial positive peak (P1; peak latency about 120 msec) followed by a later negative peak (N2; peak latency 160-200 msec). However the P1 peak dominates the pattern-reversal VEP when recorded from the midline occipital lead, where it is maximal, while the N2 peak is larger in the motion-onset VEP, especially when recorded from unipolar lateral occipital leads. Whereas the amplitude of the P1 peak in both the pattern-reversal VEP and the motion-onset VEP decreases with decreasing contrast (becoming undetectable at a contrast of about 2% for the motion-onset VEP), the amplitude of the N2 peak in both types of VEP does not vary significantly with contrast, above a contrast of 1.3%. The increase in peak latency with decreasing contrast is also more pronounced for the positive than the negative peaks of both types of VEP. Taking into account the high contrast sensitivity of the magnocellular system (thought to be involved in the processing of motion) compared with the parvocellular system (probably more concerned with the processing of form), our findings suggest that for both motion-onset and pattern-reversal VEPs the negative peak is attributable to the motion-processing magnocellular pathway and the positive peak to the form-processing parvocellular system.

Adult↗

How do thalamic axons find their way to the cortex?

A cascade of simple mechanisms influences thalamic innervation of the neocortex. The cortex exerts a remote growth-promoting influence on thalamic axons when they start to grow out, becomes growth-permissive when the axons begin to invade, and later expresses a 'stop signal', causing termination in layer 4. However, any part of the thalamus will innervate any region of developing cortex in culture, and the precise topographic distribution of thalamic fibres in vivo is unlikely to depend exclusively on regional chemoaffinity. The 'handshake hypothesis' proposes that axons from the thalamus and from early-born cortical preplate cells meet and intermingle in the basal telencephalon, whereafter thalamic axons grow over the scaffold of preplate axons, and become 'captured' for a waiting period in the subplate layer below the corresponding part of the cortex. The bizarre pattern of development of thalamic innervation in the mutant reeler mouse provides strong evidence that thalamic axons are guided by preplate axons.

Animals↗

Analysis of connectivity in the cat cerebral cortex.

The mammalian cerebral cortex is innervated by a large number of corticocortical connections. The number of connections makes it difficult to understand the organization of the cortical network. Nonetheless, conclusions about the organization of cortical systems drawn from examining connectional data have often been made in a speculative and informal manner, unsupported by any analytic treatment. Recently, progress has been made toward more systematic ways of extracting organizing principles from data on the network of connections between cortical areas of the monkey. In this article, we extend these approaches to the cortical systems of the cat. We collated information from the neuroanatomical literature about the corticocortical connections of the cat. This collation incorporated 1139 reported corticocortical connections between 65 cortical areas. We have previously used an optimization technique (Scannell and Young, 1993) to analyze this database in order to represent the connectional organization of cortical systems in the cat. Here, we report the connectional database and analyze it in a number of further ways. First, we employed rules from Felleman and Van Essen (1991) to investigate hierarchical relations among the areas. Second, we compared quantitatively the results of the optimization method with the results of the hierarchical method. Third, we examined quantitatively whether simple connection rules, which may reflect the development and evolution of the cortex, can account for the experimentally identified corticocortical connections in the database. The results showed, first, that hierarchical rules, when applied to the cat visual system, define a largely consistent hierarchy. Second, in both auditory and visual systems, the ordering of areas by hierarchical analysis and by optimization analysis was statistically significantly related. Hence, independent analyzes concur broadly in their ordering of areas in the cortical hierarchies. Third, the majority of corticocortical connections, and much of the pattern of connectivity, were accounted for by a simple "nearest-neighbor-or-next-door-but-one" connection rule, which may suggest one of the mechanisms by which the development of cortical connectivity is controlled.

Animals↗