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Colin Blakemore

Publications and source records attributed to Colin Blakemore.

36 records · Page 2Linked to original sources
PubMed2004

Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6/1 Huntington's disease transgenic mice.

Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG repeat expansion coding for an expanded polyglutamine tract in the huntingtin protein. Dendritic abnormalities occur in human HD patients and in several transgenic mouse models of the disease. In this study, we examine, for the first time, dendrite and spine pathology in the R6/1 mouse model of HD, which mimics neurodegeneration seen in human HD. Enriching the environment of HD transgenic mice delays the onset of symptoms, so we also examine the effects of enrichment on dendrite pathology. Golgi-impregnated tissue from symptomatic R6/1 HD mice reveals a decrease in dendritic spine density and dendritic spine length in striatal medium spiny neurons and cortical pyramidal neurons. HD also causes a specific reduction in the proportion of bifurcated dendritic spines on basal dendrites of cortical pyramidal neurons. No differences in soma size, recurving distal dendrites, or dendritic branching were observed. Although home-cage environmental enrichment from 1 to 8 months of age increases spine density in wild-type mice, it has no effect on the spine pathology in HD mice. These results show that dendritic spine pathology in R6/1 HD mice resembles degenerative changes seen in human HD and in other transgenic mouse models of the disease. We thus provide further evidence that the HD mutation disrupts the connectivity in both neostriatum and cerebral cortex, which will contribute to motor and cognitive disease symptoms. Furthermore, we demonstrate that Huntington's disease pathology interferes with the normal plastic response of dendritic spines to environmental enrichment.

Animals↗
PubMed2004

Pattern motion is present in V1 of awake but not anaesthetized monkeys.

We compared responses of neurons, recorded in striate cortex (area V1) of awake, fixating monkeys, to a single drifting grating with those to a 'plaid' pattern comprised of two superimposed drifting gratings separated in orientation by 90 degrees. Five out of 54 (9%) of V1 direction selective neurons responded to the direction of motion of the whole pattern [pattern motion (PM) selectivity]. Tuning curves for plaid stimuli were similar in both optimum direction and width of tuning to those for single gratings. Twenty nine out of 54 (54%) responded simply to the motion of individual orientated gratings within the pattern [component motion (CM) selectivity]. The remaining 37% (20/54) neurons were unclassified. In control experiments, 39 direction selective neurons were recorded in area V1 of anaesthetized monkey and cats. Unlike area V1 in behaving monkeys, none of these neurons exhibited PM selectivity to the drifting plaids. Twenty eight out of 39 (72%) of them responded to the direction of the component gratings and were classified as CM selectivity. Our results indicate that although most V1 neurons are CM selective, as described in anaesthetized animals, a subpopulation is clearly PM selective in behaving monkeys, reflecting integration of locally derived motion signals. Neurons in V1 therefore carry signals that may contribute to pattern motion processing and perception. This perceptual interpretation in V1 might depend much more critically on information integration mechanisms that only function properly in awake, perceiving animals.

Anesthesia↗
PubMed2004

Probing the prerequisites for motion blindness.

Neurobiological studies of visual awareness usually focus on the neural events elicited by perceived or nonperceived stimuli but neglect the preexisting conditions that allow (or prevent) conscious perception. We have examined the conditions that lead to temporary motion blindness in a rapid serial visual presentation paradigm, in which subjects have to detect coherent motion in the peripheral stream after a cue (a red fixation point) in the central stream. The failure of awareness depends critically on the occurrence of similar coherent motion events (probes) before the cue. Event-related brain potentials (ERPs) were recorded to track the processing of motion distractors, which determine the prerequisites for this transient deficit. Analysis of motion-evoked responses revealed that there is no progressive reduction in sensitivity in early visual processing. There is, however, a progressive increase in amplitude of a negative wave over the frontal cortex at approximately 250 msec after motion onset and a corresponding reduction of a centro-parietal positivity at approximately 350 msec with an increasing number of distractors. We propose that these nonsensory ERP components reflect a postperceptual frontal gating mechanism that controls the access of visual stimuli to higher order evaluation and conscious detection.

Adult↗
PubMed2003

The site of saccadic suppression.

During rapid eye movements, or saccades, stable vision is maintained by active reduction of visual sensitivity. The site of this saccadic suppression remains uncertain. Here we show that phosphenes--small illusory visual perceptions--induced by transcranial magnetic stimulation (TMS) to the human occipital cortex are immune to saccadic suppression, whereas phosphenes induced by retinal stimulation are not, thus providing direct physiological evidence that saccadic suppression occurs between the retina and the occipital visual cortex.

Adult↗
PubMed2002

Normal development of embryonic thalamocortical connectivity in the absence of evoked synaptic activity.

This study is concerned with the role of impulse activity and synaptic transmission in early thalamocortical development. Disruption of the gene encoding SNAP-25, a component of the soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor complex required for regulated neuroexocytosis, eliminates evoked but not spontaneous neurotransmitter release (Washbourne et al., 2002). The Snap25 null mutant mouse provides an opportunity to test whether synaptic activity is required for prenatal neural development. We found that evoked release is not needed for at least the gross formation of the embryonic forebrain, because the major features of the diencephalon and telencephalon were normal in the null mutant mouse. However, half of the homozygous mutants showed undulation of the cortical plate, which in the most severely affected brains was accompanied by a marked reduction of calbindin-immunoreactive neurons. Carbocyanine dye tracing of the thalamocortical fiber pathway revealed normal growth kinetics and fasciculation patterns between embryonic days 17.5 and 19. As in normal mice, mutant thalamocortical axons reach the cortex, accumulate below the cortical plate, and then start to extend side-branches in the subplate and deep cortical plate. Multiple carbocyanine dye placements in the cortical convexity revealed normal overall topography of both early thalamocortical and corticofugal projections. Electrophysiological recordings from thalamocortical slices confirmed that thalamic axons were capable of conducting action potentials to the cortex. Thus, our data suggest that axonal growth and early topographic arrangement of these fiber pathways do not rely on activity-dependent mechanisms requiring evoked neurotransmitter release. Intercellular communication mediated by constitutive secretion of transmitters or growth factors, however, might play a part.

Animals↗
PubMed2002

Correlated binocular activity guides recovery from monocular deprivation.

Monocular deprivation (MD) has much more rapid and severe effects on the ocular dominance of neurons in the primary visual cortex (V1) than does binocular deprivation. This finding underlies the widely held hypothesis that the developmental plasticity of ocular dominance reflects competitive interactions for synaptic space between inputs from the two eyes. According to this view, the relative levels of evoked activity in afferents representing the two eyes determine functional changes in response to altered visual experience. However, if the deprived eye of a monocularly deprived kitten is simply reopened, there is substantial physiological and behavioural recovery, leading to the suggestion that absolute activity levels, or some other non-competitive mechanisms, determine the degree of recovery from MD. Here we provide evidence that correlated binocular input is essential for such recovery. Recovery is far less complete if the two eyes are misaligned after a period of MD. This is a powerful demonstration of the importance of cooperative, associative mechanisms in the developing visual cortex.

Animals↗
PubMed2002

Areas of the human brain activated by ambient visual motion, indicating three kinds of self-movement.

In a positron emission tomography (PET) study, a very large visual display was used to simulate continuous observer roll, yaw, and linear movement in depth. A global analysis based on all three experiments identified brain areas that responded to the three conditions' shared characteristic of coherent, wide-field motion versus incoherent motion. Several areas were identified, in the posterior-inferior temporal cortex (Brodmann area 37), paralimbic cortex, pulvinar, and midbrain tegmentum. In addition, occipital region KO was sensitive to roll and expansion but not yaw (i.e., coherent displays containing differential flow). Continuous ambient motion did not activate V5/MT selectively. The network of sites responding specifically to coherent motion contrasted with the extensive, contiguous activation that both coherent and incoherent motion elicited in visual areas V1, V2, and V3. The coherent motion mechanisms, furthermore, extended beyond the traditional dorsal pathway proposed to account for visual motion processing, and included subcortical and limbic structures, which are implicated in polysensory processing, posture regulation, and arousal.

Adult↗
PubMed2002

Environmental enrichment slows disease progression in R6/2 Huntington's disease mice.

Huntington's disease is a genetic disorder that causes motor dysfunction, personality changes, dementia, and premature death. There is currently no effective therapy. Several transgenic models of Huntington's disease are available, the most widely used of which is the R6/2 mouse, because of its rapid disease progression. Environmental enrichment alters gene expression in the normal mouse brain, and modulates the course of several neurological disorders. Environmentally enriched mice may actually mimic human disease more accurately. We found that even limited environmental enrichment slows decline in RotaRod performance in R6/2 mice, despite rapid disease progression, whereas in normal littermates, maximal enrichment was required to induce a marked improvement in behavioral tests. Enrichment also delayed the loss of peristriatal cerebral volume in R6/2 brains. These results could provide the basis for a rational approach to ameliorate the effects of Huntington's disease.

Animals↗
PubMed2002

Integration of motion information during binocular rivalry.

When two moving gratings are superimposed in normal viewing they often combine to form a pattern that moves with a single direction of motion. Here, we investigated whether the same mechanism underlies pattern motion when drifting gratings are presented independently to the two eyes. We report that, with relatively large circular grating patches (4 deg), there are periods of monocular dominance in which one eye's orientation alone is perceived, usually moving orthogonal to the contours (component motion). But, during the transitions from one monocular view to the other, a fluid mosaic is perceived, consisting of contiguous patches, each containing contours of only one of the gratings. This entire mosaic often appears to move in a single direction (pattern motion), just as when two gratings are literally superimposed. Although this implies that motion signals from the perceptually suppressed grating continue to influence the perception of motion, an alternative possibility is that it reflects a strategy that involves integrating directional information from the contiguous single-grating patches. To test between these possibilities, we performed a second experiment with very small grating stimuli that were about the same size as the contiguous single-grating patches in the mosaic (1-deg diameter). Despite the fact that the form of only one grating was perceived, we report that pattern motion was still perceived on about one third of trials. Moreover, a decrease in the occurrence of pattern motion was apparent when the contrast and spatial frequency of the gratings were made more different from each other. This phenomenon clearly demonstrates an independent binocular interaction for form and motion.

Humans↗
PubMed2002

Is experimental motion blindness due to sensory suppression? An ERP approach.

Recent psychophysical studies have revealed attentional modulation of visual motion perception and interest now focuses on the locus of this interaction. Using event-related brain potentials (ERPs) we examined whether transient motion blindness evoked in a dual task [Vision Res. 41 (2001) 1613-1617] is related to a selection process occurring at the stage of sensory processing or at a higher level. In our paradigm, a particular change of colour of the fixation point cued the subject to detect a brief episode of coherent random dot motion embedded in a succession of episodes of incoherent motion. Detection of the coherent motion was significantly impaired when it occurred simultaneously with the colour cue, and recovered over the subsequent 300 ms. This functional relationship was reflected in the amplitude of a sensory, motion-evoked component (N200), and in a late positive complex (P300). However, a direct comparison of ERPs produced by stimuli that were detected or missed revealed differences only in the P300 component. These results indicate that attenuation of sensory motion processing does not account for this transient, attention-induced deficit in visual motion perception.

Adult↗
PubMed2002

Activity in the fusiform gyrus predicts conscious perception of Rubin's vase-face illusion.

We localized regions in the fusiform gyrus and superior temporal sulcus that were more active when subjects viewed photographs of real faces than when they viewed complex inanimate objects and other areas in the parahippocampal gyrus and the lateral occipital lobe that showed more activity during the presentation of nonface objects. Event-related functional magnetic resonance imaging was then used to monitor activity in these extrastriate visual areas while subjects viewed Rubin's vase-face stimulus and indicated switches in perception. Since the spontaneous shifts in interpretation were too rapid for direct correlation with hemodynamic responses, each reported percept (faces or vase) was prolonged by suddenly adding subtle local contrast gradients (embossing) to one side or the other of the figure-ground boundary, stabilizing the percept. Under these conditions, only face-selective areas in the fusiform gyrus responded more strongly during the perception of faces. To control for effects of the physical change to Rubin's stimulus (i.e., addition of embossing), we compared activity when the face contours were embossed after the subject had just reported the onset of perception of either faces or vase. Activity in the fusiform face area responded more strongly under the first condition, despite the fact that the physical stimulus sequences were identical. Moreover, on a trial-to-trial basis, the activity was statistically predictive of the subjects' responses, suggesting that the conscious perception of faces could be made explicit in this extrastriate visual area.

Adult↗