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Colin Blakemore

Publications and source records attributed to Colin Blakemore.

At least 19 recordsLinked to original sources
PubMed2006

The first neurons of the human cerebral cortex.

We describe a distinctive, widespread population of neurons situated beneath the pial surface of the human embryonic forebrain even before complete closure of the neural tube. These 'predecessor' cells include the first neurons seen in the primordium of the cerebral cortex, before the onset of local neurogenesis. Morphological analysis, combined with the study of centrosome location, regional transcription factors and patterns of mitosis and neurogenesis, indicates that predecessor cells invade the cortical primordium by tangential migration from the subpallium. These neurons, described here for the first time, precede all other known cell types of the developing cortex.

Body Patterning↗
PubMed2006

Activation of color-selective areas of the visual cortex in a blind synesthete.

Many areas of the visual cortex are activated when blind people are stimulated naturally through other sensory modalities (e.g., haptically; Sadato et al., 1996). While this extraneous activation of visual areas via other senses in normal blind people might have functional value (Kauffman et al., 2002; Lessard et al., 1998), it does not lead to conscious visual experiences. On the other hand, electrical stimulation of the primary visual cortex in the blind does produce illusory visual phosphenes (Brindley and Lewin, 1968). Here we provide the first evidence that high-level visual areas not only retain their specificity for particular visual characteristics in people who have been blind for long periods, but that activation of these areas can lead to visual sensations. We used fMRI to demonstrate activity in visual cortical areas specifically related to illusory colored and spatially located visual percepts in a synesthetic man who has been completely blind for 10 years. No such differential activations were seen in late-blind or sighted non-synesthetic controls; neither were these areas activated during color-imagery in the late-blind synesthete, implying that this subject's synesthesia is truly a perceptual experience.

Association↗
PubMed2006

Neurogenesis in the R6/1 transgenic mouse model of Huntington's disease: effects of environmental enrichment.

Previous work has demonstrated that the transgenic R6/1 mouse model of Huntington's disease has decreased proliferation of neural precursor cells (NPCs) in the dentate gyrus of the hippocampus. This study therefore examined the survival and differentiation of NPCs in presymptomatic and symptomatic R6/1 mice and the effects of environmental enrichment on these variables. Here it is demonstrated that the survival of bromodeoxyuridine-positive (BrdU+) NPCs in the dentate gyrus is decreased in the transgenic mice. In addition, the number of doublecortin-positive (DCX+) cells is greatly reduced in these mice, as is the total number of new mature neurons, while the proportion of BrdU+ cells differentiating into mature neurons was not significantly different between genotypes. Furthermore, the DCX+ cells in the R6/1 mice had smaller and irregular-shaped somas, shorter neurites, and migrated a shorter distance into the granular cell layer compared with wild-type mice. Older symptomatic mice housed in an enriched environment had an increased number of BrdU+ and DCX+ cells as well as longer neurites and increased migration of DCX+ cells. There was no significant difference between genotypes or environments in the number of BrdU+ cells in the subventricular zone. These results suggest that decreased neurogenesis might be responsible, in part, for the hippocampal deficits observed in these mice and that environmental enrichment produces morphological changes in newborn granule neurons in both wild-type and R6/1 mice, which could underlie some of the beneficial effects of enrichment.

Animals↗
PubMed2005

Deficits in experience-dependent cortical plasticity and sensory-discrimination learning in presymptomatic Huntington's disease mice.

Huntington's disease (HD) is one of a group of neurodegenerative diseases caused by an expanded trinucleotide (CAG) repeat coding for an extended polyglutamine tract. The disease is inherited in an autosomal dominant manner, with onset of motor, cognitive, and psychiatric symptoms typically occurring in midlife, followed by unremitting progression and eventual death. We report here that motor presymptomatic R6/1 HD mice show a severe impairment of somatosensory-discrimination learning ability in a behavioral task that depends heavily on the barrel cortex. In parallel, there are deficits in barrel-cortex plasticity after a somatosensory whisker-deprivation paradigm. The present study demonstrates deficits in neocortical plasticity correlated with a specific learning impairment involving the same neocortical area, a finding that provides new insight into the cellular basis of early cognitive deficits in HD.

Age Factors↗
PubMed2005

Tangential networks of precocious neurons and early axonal outgrowth in the embryonic human forebrain.

We used a combination of immunohistochemistry and carbocyanine dye tracing to study neurons and their processes in the human embryonic forebrain, 4-7 weeks after conception, before the onset of synaptogenesis. We discovered a widespread network of precocious MAP2 (microtubule-associated protein 2)-immunoreactive cells, with long, nonaxonal processes, before the appearance of the cortical plate and the establishment of thalamocortical connectivity. Dye tracing revealed that the processes of these precocious cells form tangential links between intermediate zones of the thalamus, ganglionic eminence, hypothalamus, and cortical preplate. The spatiotemporal distribution and morphology of the precocious neurons in the cortical preplate suggest that they are generated outside the cerebral wall rather than in the local ventricular zone. The first thalamocortical axons and axons of preplate cells extend across diencephalo-telencephalic and striatocortical boundaries before the arrival of the first cortical plate neurons. Precocious cells may provide initial communication between subdivisions of the embryonic brain as well as guidance cues for navigation of growing axons and/or transverse neuronal migration.

Age Factors↗
PubMed2005

International perspectives on engaging the public in neuroethics.

With an ever-increasing understanding of the brain mechanisms associated with core human attributes and values, there is an increasing public interest in the results of neuroscience research and the ways in which that new knowledge will be used. Here, we present perspectives on engaging the public on these issues on an international scale, the role of the media, and prospects for the new field of neuroethics as both a focus and a driver of these efforts.

Bioethical Issues↗
PubMed2005

Activity-dependent regulation of synapse and dendritic spine morphology in developing barrel cortex requires phospholipase C-beta1 signalling.

The phospholipase C-beta1 (PLC-beta1) signalling pathway, activated via metabotropic glutamate receptors (mGluRs), is implicated in activity-dependent development of the cerebral cortex, as both PLC-beta1 and mGluR5 knockout mice exhibit disrupted barrel formation in somatosensory cortex. To characterize the effects of this signalling system on development of synaptic circuitry in barrel cortex, we have examined neuronal ultrastructure, synapse formation and dendritic spine morphology in PLC-beta1 knockout mice. Qualitative ultrastructure of neurons and synapse density in layers 2-4 of barrel cortex were unchanged in PLC-beta1 knockout mice during development [postnatal day (P) 5] and in mature cortex (P19-21). We found a decrease in the proportion of synapses with symmetric morphology at P5 that was gone by P19-21, indicating a transient imbalance in excitatory and inhibitory circuitry. We also investigated dendritic spines by back-labelling layer 5 pyramidal neurons with carbocyanine. We observed normal dendritic spine densities on apical dendrites as they passed through layer 4 of barrel cortex, but spine morphology was altered in PLC-beta1 knockout mice at P9. These observations indicate that the PLC-beta1 signalling pathway plays a role in the development of normal cortical circuitry. Interrupting this regulation leads to changes in synapse and dendritic spine morphology, possibly altering post-synaptic integration of signal.

Algorithms↗
PubMed2005

Cognitive disorders and neurogenesis deficits in Huntington's disease mice are rescued by fluoxetine.

Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat encoding an extended polyglutamine tract in the huntingtin protein. Affected individuals display progressive motor, cognitive and psychiatric symptoms (including depression), leading to terminal decline. Given that transgenic HD mice have decreased hippocampal cell proliferation and that a deficit in neurogenesis has been postulated as an underlying cause of depression, we hypothesized that decreased hippocampal neurogenesis contributes to depressive symptoms and cognitive decline in HD. Fluoxetine, a serotonin-reuptake inhibitor commonly prescribed for the treatment of depression, is known to increase neurogenesis in the dentate gyrus of wild-type mouse hippocampus. Here we show that hippocampal-dependent cognitive and depressive-like behavioural symptoms occur in HD mice, and that the administration of fluoxetine produces a marked improvement in these deficits. Furthermore, fluoxetine was found to rescue deficits of neurogenesis and volume loss in the dentate gyrus of HD mice.

Age Factors↗
PubMed2004

Decreased hippocampal cell proliferation in R6/1 Huntington's mice.

In order to ascertain whether disturbances of neurogenesis occur in chronic neurodegenerative disorders, we assessed hippocampal cell proliferation in the R6/1 transgenic mouse model of Huntington's disease (HD). Using BrdU labelling for dividing cells at two different time points (5 and 20 weeks) in transgenic and wild type control mice, we have shown that cell proliferation in the hippocampus was similar in younger asymptomatic R6/1 mice and wild type controls, but that older R6/1 mice had significantly fewer BrdU cells than controls. Such a decrease in cell proliferation may be relevant to some of the deficits seen in these mice, although further work is needed to prove this.

Age Factors↗
PubMed2004

Environmental enrichment rescues protein deficits in a mouse model of Huntington's disease, indicating a possible disease mechanism.

Huntington's disease (HD) is a devastating neurodegenerative disorder caused by a CAG repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. Transgenic mice expressing a human huntingtin transgene containing an expanded CAG repeat (R6/1 model) develop a neurodegenerative disorder closely resembling human HD. Previous work demonstrated that environmental enrichment delays the onset of motor symptoms in this mouse model. We confirmed that at 5 months of age, enrichment ameliorates motor symptoms (assessed using the rotarod test) and prevents loss of body weight induced by the HD transgene. We further examined molecular consequences of enrichment by determining changes in protein levels in the neostriatum, hippocampus, and anterior cortex using quantitative Western blot analysis. Non-enriched HD mice have severe reductions in BDNF in the hippocampus and striatum at 5 months, which are entirely rescued by enrichment. BDNF levels are unaltered by HD in the anterior cortex, suggesting that enrichment might prevent HD-induced impairment of anterograde transport of this neurotrophin to the striatum. NGF is unaffected by HD. Non-enriched HD mice also exhibit deficits in dopamine and cAMP-regulated phosphoprotein (32 kDa) in striatum and anterior cortex. Environmental enrichment rescues the cortical but not the striatal deficit at 5 months. These results suggest that environmental enrichment benefits animals at early stages of the disease by rescuing protein deficits, possibly through rescuing transcription or protein transport problems.

Age Factors↗
PubMed2004

Impaired learning-dependent cortical plasticity in Huntington's disease transgenic mice.

Huntington's disease (HD) is a genetically transmitted neurodegenerative disorder. The neuropathology in HD is a selective neuronal cell death in several brain regions including cortex. Although changes in synaptic plasticity were shown within the hippocampus and striatum of HD transgenic mice, there are no studies considering neocortical synaptic plasticity abnormalities in HD. We examined the impact of the HD transgene upon learning-dependent plasticity of cortical representational maps. The effect of associative learning, in which stimulation of a row of vibrissae was paired with appetitive stimulus, upon functional representations of vibrissae in the barrel cortex, was investigated with 2-deoxyglucose brain mapping in presymptomatic R6/1 HD mice. In wild-type mice, cortical representation of the row of vibrissae involved in the training was expanded, while in HD mice the representation of this row was not expanded. The results suggest that presymptomatic R6/1 HD transgenic mice show deficits in plasticity of primary somatosensory cortex.

Animals↗
PubMed2004

Visual synaesthesia in the blind.

Synaesthesia is characterised by idiosyncratic ectopic sensations which commonly take the form of coloured visual impressions evoked by touch or hearing. We studied six late-blind individuals who have retained synaesthetic colour perception. Four of them had been without any form of genuine colour vision for more than 10 years. All perceived colours when they heard or thought about letters, numbers, and time-related words (days of the week and months of the year). One experienced synaesthetic colours for all words. Another saw Braille characters as coloured dots when he touched them. The aberrant experiences were compelling and reliable: detailed verbal descriptions of the colours were remarkably consistent in tests more than 2 months apart. The percepts predominantly took the form of coloured patches, localised in body-centred space for five of the subjects and in head-centred space for the sixth. This implies that the neural activity underlying synaesthesia occurs after the establishment of a visual representation independent of eye (or head) position. The synaesthetic colour depended only on phonetic cues in one case, but on semantic context in others. Although synaesthesia might be due to idiosyncratic, aberrant corticocortical connectivity established during early development, it can persist for very long periods with little or no natural experience in the referred modality and therefore does not depend solely on continuing associative learning.

Aged↗