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PubMed1998

The objects of action and perception.

Two major functions of the visual system are discussed and contrasted. One function of vision is the creation of an internal model or percept of the external world. Most research in object perception has concentrated on this aspect of vision. Vision also guides the control of object-directed action. In the latter case, vision directs our actions with respect to the world by transforming visual inputs into appropriate motor outputs. We argue that separate, but interactive, visual systems have evolved for the perception of objects on the one hand and the control of actions directed at those objects on the other. This 'duplex' approach to high-level vision suggests that Marrian or 'reconstructive' approaches and Gibsonian or 'purposive-animate-behaviorist' approaches need not be seen as mutually exclusive, but rather as complementary in their emphases on different aspects of visual function.

Animals↗
PubMed2002

A label-free optical technique for detecting small molecule interactions.

A novel approach for the label-free detection of molecular interactions is presented in which a colorimetric resonant grating is used as a surface binding platform. The grating, when illuminated with white light, is designed to reflect only a single wavelength. When molecules are attached to the surface, the reflected wavelength (color) is shifted due to the change of the optical path of light that is coupled into the grating. By linking receptor molecules to the grating surface, complementary binding molecules can be detected without the use of any kind of fluorescent probe or radioactive label. The detection technique is capable of detecting the addition and removal of small molecules as they interact with receptor molecules on the sensor surface or enzymes in the solution surrounding the sensor. Two assays are presented to exemplify the detection of small molecule interactions with the biosensor. First, an avidin receptor layer is used to detect 244 Da biotin binding. Second, a protease assay is performed in which a 136 Da p-nitroanilide (pNA) moeity is cleaved from an immobilized substrate. Because the sensor structure can be embedded in the plastic surfaces of microtiter plates or the glass surfaces of microarray slides, it is expected that this technology will be most useful in applications where large numbers of biomolecular interactions are measured in parallel, particularly when molecular labels will alter or inhibit the functionality of the molecules under study. Screening of pharmaceutical compound libraries with protein targets, and microarray screening of protein-protein interactions for proteomics are examples of applications that require the sensitivity and throughput afforded by this approach.

Avidin↗
PubMedDate not supplied

Retinotopic organization of the superior colliculus in relation to the retinal distribution of afferent ganglion cells.

Sensory representations in the brain exhibit topographic variations in magnification. These variations have been thought to reflect regional differences in the density of innervation at the sensory receptor surface. In the primate visual cortex, for example, local magnification factors have been reported to be proportional to the corresponding densities of retinal ganglion cells. We sought to learn whether this principle also operates in a second major retinofugal pathway--the projection to the superior colliculus. In cats, we first used retrograde transport to determine the retinal distributions of the ganglion cells that project to the colliculus. Then, we compared the numbers of colliculopetal ganglion cells in selected retinal sectors to the areas of the corresponding collicular representations. Collicular areal magnification was not simply proportional to the density of afferent ganglion cells, being instead at least 5-fold greater than expected in the representation of the central visual field. These data imply that incoming retinal afferents are more widely spaced in the central regions of the tectal map than in the map's periphery. Such variations in afferent density appear to play as large a role as the distribution of ganglion cells in determining the metric of the collicular map.

Afferent Pathways↗
PubMed2005

Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex.

Neurons in the cerebral cortex are organized into anatomical columns, with ensembles of cells arranged from the surface to the white matter. Within a column, neurons often share functional properties, such as selectivity for stimulus orientation; columns with distinct properties, such as different preferred orientations, tile the cortical surface in orderly patterns. This functional architecture was discovered with the relatively sparse sampling of microelectrode recordings. Optical imaging of membrane voltage or metabolic activity elucidated the overall geometry of functional maps, but is averaged over many cells (resolution >100 microm). Consequently, the purity of functional domains and the precision of the borders between them could not be resolved. Here, we labelled thousands of neurons of the visual cortex with a calcium-sensitive indicator in vivo. We then imaged the activity of neuronal populations at single-cell resolution with two-photon microscopy up to a depth of 400 microm. In rat primary visual cortex, neurons had robust orientation selectivity but there was no discernible local structure; neighbouring neurons often responded to different orientations. In area 18 of cat visual cortex, functional maps were organized at a fine scale. Neurons with opposite preferences for stimulus direction were segregated with extraordinary spatial precision in three dimensions, with columnar borders one to two cells wide. These results indicate that cortical maps can be built with single-cell precision.

Analysis of Variance↗
PubMed2002

Spatial coding of position and orientation in primary visual cortex.

We examined the spatial distribution of population activity in primary visual cortex (V1) of tree shrews with optical imaging and electrophysiology. A line stimulus, thinner than the average V1 receptive field, evoked a broad strip of neural activity of nearly constant size for all stimulus locations tested within the central 10 degrees of visual space. Stimuli in adjacent positions activated highly overlapping populations of neurons; nevertheless, small changes in stimulus position produced orderly changes in the location of the peak of the population response. Statistically significant shifts in the population response were found for stimulus displacements an order of magnitude smaller than receptive field width, down to the limit of optical imaging resolution. Based on the pattern of population activity, we conclude that the map of visual space in V1 is orderly at a fine scale and has uniform coverage of position and orientation without local relationships in the mapping of these features.

Action Potentials↗
PubMed2005

Spatiotemporal evolution of functional hemodynamic changes and their relationship to neuronal activity.

Brain imaging techniques such as functional magnetic resonance imaging (fMRI) have provided a wealth of information about brain organization, but their ability to investigate fine-scale functional architecture is limited by the spatial specificity of the hemodynamic responses upon which they are based. We investigated the spatiotemporal evolution of hemodynamic responses in rat somatosensory cortex to electrical hindpaw stimulation. We combined the advantages of optical intrinsic signal imaging and spectroscopy to produce high-resolution two-dimensional maps of functional changes in tissue oxygenation and blood volume. Cerebral blood flow changes were measured with laser-Doppler flowmetry, and simultaneously recorded field potentials allowed comparison between hemodynamic changes and underlying neuronal activity. For the first 2 to 3 secs of activation, hemodynamic responses overlapped in a central parenchymal focus. Over the next several seconds, cerebral blood volume changes propagated retrograde into feeding arterioles, and oxygenation changes anterograde into draining veins. By 5 to 6 secs, responses localized primarily in vascular structures distant from the central focus. The peak spatial extent of the hemodynamic response increased linearly with synaptic activity. This spatial spread might be because of lateral subthreshold activation or passive vascular overspill. These results imply early microvascular changes in volume and oxygenation localize to activated neural columns, and that spatial specificity will be optimal within a 2- to 3-sec window after neuronal activation.

Animals↗
PubMed2000

Cellular response to texture and form defined by motion in area 19 of the cat.

The present study examined the neuronal sensitivity in area 19 of the cat to a motion-defined bar and to texture. Sensitivity was tested in normal, lesioned (areas 17-18) and split-chiasm cats using a kinematogram, as well as a textured bar drifting on a uniform light background and a light bar drifting on a stationary textured background. Texture density was varied. The results indicate that almost all cells of area 19 recorded in the three groups of cats responded to a motion-defined bar or to its edges. Texture density influenced the responses in that the discharge rate increased as density decreased. However, the majority of cells were sensitive to the highest texture density kinematogram. Moreover, the neural responses of all cats were either independent of the density of the textured bar or background, or were modulated by it. These results show that cells in area 19 can signal the presence of a kinetic bar and that the density of either the textured bar, the background or both can influence figure-ground detection. The results are interpreted with respect to how various inputs influence the function of area 19.

Animals↗
PubMed1998

Functional analysis of primary visual cortex (V1) in humans.

Human area V1 offers an excellent opportunity to study, using functional MRI, a range of properties in a specific cortical visual area, whose borders are defined objectively and convergently by retinotopic criteria. The retinotopy in V1 (also known as primary visual cortex, striate cortex, or Brodmann's area 17) was defined in each subject by using both stationary and phase-encoded polar coordinate stimuli. Data from V1 and neighboring retinotopic areas were displayed on flattened cortical maps. In additional tests we revealed the paired cortical representations of the monocular "blind spot." We also activated area V1 preferentially (relative to other extrastriate areas) by presenting radial gratings alternating between 6% and 100% contrast. Finally, we showed evidence for orientation selectivity in V1 by measuring transient functional MRI increases produced at the change in response to gratings of differing orientations. By systematically varying the orientations presented, we were able to measure the bandwidth of the orientation "transients" (45 degrees).

Brain Mapping↗
PubMed2006

Neural processes underlying memory attribution on a reality-monitoring task.

A relatively common form of memory distortion arises when individuals must discriminate items they have seen from those they have imagined (reality monitoring). The present fMRI investigation (at 1.5 T) focused on the processes that relate to memory assignment regardless of accuracy (e.g. that correspond with the belief that an item was presented as a picture, regardless of whether that belief is correct). Prior to the scan, participants (n = 16) viewed concrete nouns and formed mental images of the object named. Half of the names were followed by the object's photo. During the scan, participants saw the object names and indicated whether the corresponding photo had been studied. Activity in visual-processing regions (including the precuneus and fusiform gyrus) corresponded with the attribution of an item to a pictorial presentation. In contrast, activity in regions thought to be important for self-referential processing (including the ventromedial prefrontal cortex and posterior cingulate gyrus) was associated with attribution to a nonpresented source. These neural findings converge with behavioral evidence indicating that individuals use the amount of different types of information retrieved (e.g. perceptual detail, information about cognitive operations) to determine whether an item was imagined or perceived.

Adult↗
PubMed2005

Positioning of retinotopic areas and patterning of cerebral cortex layout.

We examined the positioning of human retinotopic areas, which were considered to be homologous with the macaque visual cortices, by applying computational geometry to MRI and fMRI data sets. We found a similarity between the positional relationship of the retinotopic areas in the human and macaque visual cortex, despite the large difference in brain size. This suggests that area maps in different species may share topological features, probably resulting from broad similarities in the patterning mechanism of cerebral cortex layout.

Animals↗
PubMed1994

repo encodes a glial-specific homeo domain protein required in the Drosophila nervous system.

We report the identification of a Drosophila locus, reversed polarity (repo). Weak repo alleles were viable but affected glia in the optic lobe, resulting in a reversal in polarity of the electrophysiological to light in the adult. Strong repo alleles caused defects in embryonic glia and resulted in embryonic lethality. Expression of repo appeared to be specific to glia throughout development. In the adult visual system, repo was expressed in laminal glia, medullar glia, and subretinal cells; in the embryo, repo was expressed in nearly all of the identified glia in the central and peripheral nervous systems except midline glia. The repo gene encoded a homeo domain protein suggesting that it might be a transcriptional regulator of genes required for glial development.

Amino Acid Sequence↗
PubMed2006

Magnetically induced phonon anisotropy in ZnCr2O4 from first principles.

We have studied the influence of magnetic order on the optical phonons of the geometrically frustrated spinel ZnCr2O4 within density-functional theory. By mapping local spin density approximation plus Hubbard U (LSDA + U) phonon calculations onto a Heisenberg-like model, we developed a method to calculate exchange derivatives and subsequently the spin-phonon coupling parameter from first principles.

Journal Article↗
PubMedDate not supplied

Method used to measure interaction of proteins with dual-beam optical tweezers.

In the force measurement of protein-protein interaction, proteins are usually attached to microbeads, so the coated beads serve as both handles and force transducers. Due to the short interaction distance between proteins, the beads are usually close enough to each other. When dual-beam optical tweezers and quadrant photodiode detector are used to investigate the interaction of proteins, it is found that the signal of detected beads is greatly affected by adjacent beads. Analysis reveals that the contribution of two beads to the quadrant detector signal is independent. A method for extracting the real interaction signal from a disturbed one is presented. Based on this method, interaction between microtubules and AtMAP65-1 is measured. The results show that this method is useful for measuring short-distance interaction with the precision of piconewton and nanometer scales.

Arabidopsis Proteins↗
PubMed2005

Proteomic identification of oxidatively modified retinal proteins in a chronic pressure-induced rat model of glaucoma.

PURPOSE: Based on the evidence of an amplified production of reactive oxygen species (ROS) during glaucomatous neurodegeneration, proteomic analysis was performed to determine oxidative modification of retinal proteins after experimental elevation of intraocular pressure (IOP). METHODS: IOP elevation was induced in rats by hypertonic saline injections into episcleral veins. Protein expression was determined by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) of retinal protein lysates obtained from eyes matched for the cumulative IOP exposure and axon loss. To determine protein oxidation levels, protein carbonyls were detected through 2D-oxyblot analysis of 2,4-dinitrophenylhydrazine (DNPH)-treated samples using an anti-DNP antibody. For identification of oxidized proteins, peptide masses were analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) and liquid chromatography-tandem mass spectrometry (LC/MS/MS). In addition to use of different engines in a bioinformatic database search and performance of peptide sequencing and 2D-Western blot analysis for confirmation of the identified proteins, immunohistochemistry was used for further validation of the proteomic findings. RESULTS: Comparison of 2D-oxyblots with Coomassie Blue-stained 2D-gels revealed that approximately 60 protein spots obtained with retinal protein lysates from ocular hypertensive eyes (of >400 spots) exhibited protein carbonyl immunoreactivity, which reflects oxidatively modified proteins. There was a significant increase in anti-carbonyl reactivity in individual protein spots obtained with retinal protein lysates from ocular hypertensive eyes compared with the control (P < 0.01). The identified proteins through peptide mass fingerprinting and peptide sequencing included glyceraldehyde-3-phosphate dehydrogenase, a glycolytic enzyme; HSP72, a stress protein; and glutamine synthetase, an excitotoxicity-related protein. Immunolabeling of retina sections with specific antibodies demonstrated cellular localization of these proteins as well as retinal distribution of the increased protein carbonyl immunoreactivity in ocular hypertensive eyes. CONCLUSIONS: The findings of this in vivo study provide novel evidence for oxidative modification of many retinal proteins in ocular hypertensive eyes and identify three specific targets of retinal protein oxidation in these eyes, thereby supporting the association of oxidative damage with neurodegeneration in glaucoma. By using a proteomic approach, this study also exemplifies that proteomics provide a very promising way to elucidate pathogenic mechanisms in glaucoma at the protein level.

Animals↗
PubMed2004

Cellular mechanisms associated with spontaneous and ciliary neurotrophic factor-cAMP-induced survival and axonal regeneration of adult retinal ganglion cells.

We have shown previously that intraocular elevation of cAMP using the cAMP analog 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) failed to promote axonal regeneration of axotomized adult retinal ganglion cells (RGCs) into peripheral nerve (PN) grafts but significantly potentiated ciliary neurotrophic factor (CNTF)-induced axonal regeneration. Using the PN graft model, we now examine the mechanisms underlying spontaneous and CNTF/CPT-cAMP-induced neuronal survival and axonal regrowth. We found that blockade of the cAMP pathway executor protein kinase A (PKA) using the cell-permeable inhibitor KT5720 did not affect spontaneous survival and axonal regeneration but essentially abolished the CNTF/CPT-cAMP-induced RGC survival and axonal regeneration. Blockade of CNTF signaling pathways such as phosphotidylinositol 3-kinase (PI3K)/akt by 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) by 2-(2-diamino-3-methoxyphenyl-4H-1-benzopyran-4-one (PD98059), or Janus kinase (JAK)/signal transducer and activators of transcription (STAT3) by tyrphostin AG490 also blocked the CNTF/CPT-cAMP-dependent survival and regeneration effects. PKA activity assay and Western blots showed that KT5720, LY294002, and PD98059 almost completely inhibited PKA, PI3K/akt, and MAPK/ERK signal transduction, respectively, whereas AG490 substantially decreased JAK/STAT3 signal transduction. Intraocular injection of CPT-cAMP resulted in a small PKA-dependent increase in CNTF receptor alpha mRNA expression in the retinas, an effect that may facilitate CNTF action on survival and axonal regeneration. Surprisingly, in the absence of CNTF/CPT-cAMP, LY294002, PD98059, and AG490, but not KT5720, significantly enhanced spontaneous RGC survival, suggesting differential roles of these pathways in RGC survival under different conditions. Our data suggest that CNTF/CPT-cAMP-induced RGC survival and axonal regeneration are a result of multiple pathway actions, with PKA as an essential component, but that these pathways can function in an antagonistic manner under different conditions.

Animals↗