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PubMed2005

Genetic and phenotypic analysis of Tcm, a mutation affecting early eye development.

Tcm (total cataract with microphthalmia) is an autosomal dominant mouse eye mutation. Heterozygous Tcm/+ mice are born with several eye malformations including microphthalmia, retinal and iris dysplasia, total lens cataract, and ventral coloboma. The Tcm mutation was previously mapped to a 26-Mb region on Chr 4 between D4Mit235 and D4Mit106. In this study, we characterize the Tcm/ Tcm homozygous mutant and find they are viable but severely microphthalmic. The developing eye in the Tcm/Tcm homozygote shows defects during early eye development, before formation of the optic cup. Further genetic mapping reduced the Tcm critical region to a 1.3-Mb region bordered by SNPs rs3666764 and rs3713818. This critical region contains two known genes (Asph and Gfd6) and three predicted genes, all of which are positional candidates for Tcm. Sequence analysis of Tcm genomic DNA revealed no mutations in the coding regions and splice site junctions of the five candidate genes. These results indicate that the causitive Tcm mutation falls within a noncoding regulatory region of one of the five candidate genes or in an undescribed gene.

Aging↗
PubMed1978

Deflection of selected optic fibers into a denervated tectum in goldfish.

In goldfish, one eye was enucleated, and after two or more weeks a select fraction of optic fibers from the remaining eye was deflected into the ipsilateral optic tectum. At varying intervals, the optic reinnervation of the ipsilateral tectum was measured by autoradiography and electrophysiologic mapping. Both methods indicated the deflected optic fibers not only innervated the appropriate region of tectum but also spread beyond this, occupying a total area that was several times greater than normal. Correlated with this spreading were low grain density in the autoradiograms and reduction in the number of amplitudes of units recorded electrophysiologically. The electrophysiology also revealed this projection to be almost devoid of topographic organization, showing only a crude but appropriate polarity.

Animals↗
PubMed1998

Role for cell adhesion and glycosyl (HNK-1 and oligomannoside) recognition in the sharpening of the regenerating retinotectal projection in goldfish.

Cell-adhesion molecules (CAMs) are thought to play crucial roles in development and plasticity in the nervous system. This study tested for a role for cell adhesion and in particular, the recognition of two glycosyl epitopes (HNK-1 and oligomannoside) in the activity-driven sharpening of the retinotopic map formed by the regenerating retinal fibers of goldfish. HNK-1 is a prominent glycosyl epitope on many CAMs and extracellular matrix (ECM) molecules, including NCAM, L1, ependymin, and integrins, which have all been implicated in synaptic plasticity. To test for a role of HNK-1 in the sharpening process, we used osmotic minipumps to infuse HNK-1 antibodies for 7-21 days into the tectal ventricle starting at 18 days after optic nerve crush. Retinotopic maps recorded at 76-86 days postcrush showed a lack of sharpening similar to that seen previously with two antibodies to ependymin, an HNK-1-positive ECM component present in cerebrospinal fluid. The multiunit receptive fields at each point averaged 26 degrees versus 11-12 degrees in regenerates infused with control antibodies or Ringer's alone. The HNK-1 epitope also binds to the G2 domain of laminin to mediate neuron-ECM adhesion. To test for a role for laminin, a polyclonal antibody was similarly infused and also prevented sharpening to approximately the same degree. The results support a role for the HNK-1 epitope and laminin in retinotectal sharpening. The oligomannoside epitope (recognized by monoclonal antibody L3) on the CAM L1 interacts with NCAM on the same cell to promote stronger L1 homophilic interactions between cells. Both an L1-like molecule and NCAM are prominently reexpressed in the regenerating retinotectal system of fish. Infusion of oligomannosidic glycopeptides resulted in decreased sharpening, with multiunit receptive fields that averaged 22.7 degrees. Infusions of mannose-poor glycopeptides less prominently disrupted sharpening, with average multiunit receptive fields of 18 degrees. Thus, oligomannosidic glycans in particular may play a role in retinotopic sharpening. Blocking glycan-mediated interactions between CAMs and ECM molecules could decrease the extent of exploratory growth of retinal axon collaterals, preventing them from finding their retinotopic sites, or could interfere with L1 or NCAM and laminin binding at the synaptic densities preventing stabilization of retinotopically appropriate synapses. Together, these results support a prominent role for cell adhesion and glycan epitopes in visual synaptic plasticity.

Animals↗
PubMed2004

[Investigation of PP/PE blend with FTIR mapping].

The polypropylene/polyethylene (PP/PE) blends with different weight ratio were studied by FTIR spectroscopy. The characteristic absorption bands of PP and PE in different blends were compared. It was found that the ratio of the characteristic absorption peak areas of PP to those of PE is correlated with the weight ratio of PP to PE in the blends. Based on the above results, FTIR mapping technique was applied to characterize the samples prepared by embedding PP fiber into molten PE film, and the distribution of PP and PE in the blends can be obtained from the ratio of the characteristic peak areas of PP to PE. Good agreements have been observed between the IR mapping image and the image obtained using polarized optical microscope. These results indicated that FTIR mapping technique is an effective tool to investigate the phase separation behavior of polymer blends based on the ratio of the characteristic peak areas of different polymers.

English Abstract↗
PubMed2003

Optical topography: practical problems and new applications.

We will briefly review the present status of optical topography and then discuss the method of improving practicality, i.e., the signal-to-noise (S/N) ratio and the spatial resolution in observations of higher-order brain functions. The optimum wavelength pair improved the S/N ratio sixfold for deoxyhemoglobin, and new configurations of light irradiation and detection positions doubled the spatial resolution. We also report on developing application fields of optical topography. This modality will bridge the gap between natural sciences, neuroscience, and pedagogy, and show actual real-time brain activity.

Brain↗
PubMed2000

Dynamics of wavelets and their role in atrial fibrillation in the isolated sheep heart.

BACKGROUND: The multiple wavelet hypothesis is the most commonly accepted mechanism underlying atrial fibrillation (AF). However, high frequency periodic activity has recently been suggested to underlie atrial fibrillation in the isolated sheep heart. We hypothesized that in this model, multiple wavelets during AF are generated by fibrillatory conduction away from periodic sources and by themselves may not be essential for AF maintenance. METHODS AND RESULTS: We have used a new method of phase mapping that enables identification of phase singularities (PSs), which flank individual wavelets during sustained AF. The approach enabled characterization of the initiation, termination, and lifespan of wavelets formed as a result of wavebreaks, which are created by the interaction of wave fronts with functional and anatomical obstacles in their path. AF was induced in six Langendorff-perfused sheep hearts in the presence of acetylcholine. High resolution video imaging was utilized in the presence of a voltage sensitive dye; two-dimensional phase maps were constructed from optical recordings. The major results were as follows: (1) the critical inter-PS/wavelet distance for the formation of rotors was 4 mm, (2) the spatial distribution of wavelets/PSs was non-random. (3) the lifespan of PSs/wavelets was short; 98% of PSs/wavelets existed for < 1 rotation, and (4) the mean number of waves that entered our mapping field (15.7 +/- 1.6) exceeded the mean number of waves that exited it (9.7 +/- 1.5; P < 0.001). CONCLUSIONS: Our results strongly suggest that multiple wavelets may result from breakup of high frequency organized waves in the isolated Langendorff-perfused sheep heart, and as such are not a robust mechanism for the maintenance of AF in our model.

Acetylcholine↗
PubMed2004

A review of approaches for classifying benthic habitats and evaluating habitat quality.

We have assessed the current state of knowledge relative to methods used in assessing sub-tidal benthic habitat quality and the classification of benthic habitats. While our main focus is on marine habitat, we extensively draw on knowledge gained in freshwater systems where benthic assessment procedures are at an advanced stage of maturity. We found a broad range of sophistication/complication in terms of the methods applied in assessing and mapping benthic habitats. The simplest index or metric involved some assessment of species richness, while the most complicated required utilizing multi-variate analysis. The simplest mapping attempts equated physical substrate with benthic habitat while the most sophisticated relied on extensive environmental preference and groundtruth data for species of concern. The leading edge of methods for benthic habitat mapping involves combining the advances in optical and acoustic methods that allow for routine classifying and mapping of the seafloor with biological and habitat data for species of concern. The objective of this melding of dispirit methods is to produce benthic habitat maps with broad system wide coverage and sound biological underpinning. It is clear that the disparity in information density between the physical and biological sides of the equation currently hinder applicability and acceptability of benthic habitat mapping efforts. In addition to the lack of basic information on the biological and environmental tolerances of targeted species, the proliferation of metrics for characterizing and assessing biological conditions further clouds the usefulness of any broad scale mapping attempt. The problem of data density mismatch between physical and biological methods will likely not be solved until acoustic methods can routinely resolve the elusive biological components that make a physical substrate a habitat.

Animals↗
PubMed2000

An analysis of orientation and ocular dominance patterns in the visual cortex of cats and ferrets.

We report an analysis of orientation and ocular dominance maps that were recorded optically from area 17 of cats and ferrets. Similar to a recent study performed in primates (Obermayer & Blasdel, 1997), we find that 80% (for cats and ferrets) of orientation singularities that are nearest neighbors have opposite sign and that the spatial distribution of singularities deviates from a random distribution of points, because the average distances between nearest neighbors are significantly larger than expected for a random distribution. Orientation maps of normally raised cats and ferrets show approximately the same typical wavelength; however, the density of singularities is higher in ferrets than in cats. Also, we find the well-known overrepresentation of cardinal versus oblique orientations in young ferrets (Chapman & Bonhoeffer, 1998; Coppola, White, Fitzpatrick, & Purves, 1998) but only a weak, not quite significant overrepresentation of cardinal orientations in cats, as has been reported previously (Bonhoeffer & Grinvald, 1993). Orientation and ocular dominance slabs in cats exhibit a tendency of being orthogonal to each other (Hubener, Shoham, Grinvald, & Bonhoeffer, 1997), albeit less pronounced, as has been reported for primates (Obermayer & Blasdel, 1993). In chronic recordings from single animals, a decrease of the singularity density and an increase of the ocular dominance wavelength with age but no change of the orientation wavelengths were found. Orientation maps are compared with two pattern models for orientation preference maps: bandpass-filtered white noise and the field analogy model. Bandpass-filtered white noise predicts sign correlations between orientation singularities, but the correlations are significantly stronger (87% opposite sign pairs) than what we have found in the data. Also, bandpass-filtered noise predicts a deviation of the spatial distribution of singularities from a random dot pattern. The field analogy model can account for the structure of certain local patches but not for the whole orientation map. Differences between the predictions of the field analogy model and experimental data are smaller than what has been reported for primates (Obermayer & Blasdel, 1997), which can be explained by the smaller size of the imaged areas in cats and ferrets.

Algorithms↗
PubMed2005

Orientation-restricted continuous visual exposure induces marked reorganization of orientation maps in early life.

To elucidate the effect of visual experience on the development of orientation maps, we conducted intrinsic signal optical imaging of the visual cortex of kittens that were continuously exposed to a single orientation through cylindrical-lens-fitted goggles under a freely moving condition starting at post-natal week 3. We observed a rapid reorganization of orientation maps, characterized by extensive representation of exposed orientations with reduced responsiveness to unexposed orientations. The over-representation of exposed orientation was marked for 1-2 weeks of goggle rearing. A longer period of goggle rearing, however, decreased the degree of over-representation, which still remained at a remarkable level. Dark rearing episodes daily interleaved between single orientation exposures moderated the over-representation effect. Unit recording from goggle-reared kittens showed preferred orientations consistent with optical imaging. Using c-Fos immunoreactivity mapping, we showed that the number of neurons strongly responding to the exposed orientation was 3 times larger in a goggle-reared cat than the number of neurons responding to the vertical orientation in a normal cat. Taken together, these results suggest that the reorganization of orientation maps was caused by the expansion of domains maximally responding to exposed orientation as well as the strong reduction of responses to unexposed orientations.

Algorithms↗
PubMed2006

Mapping iso-orientation columns by contrast agent-enhanced functional magnetic resonance imaging: reproducibility, specificity, and evaluation by optical imaging of intrinsic signal.

Activation resembling ocular dominance or orientation columns has been mapped with high-resolution functional magnetic resonance imaging (fMRI). However, the neuronal interpretation of these functional maps is unclear because of the poor sensitivity of fMRI, unknown point spread function (PSF), and lack of comparison with independent techniques. Here we show that cerebral blood volume (CBV)-weighted fMRI with a blood plasma contrast agent (monocrystalline iron oxide nanoparticles), in combination with continuous temporally encoded stimulation, can map columnar neuronal activity in the cat primary visual cortex with high sensitivity, selectivity, and reproducibility. We examined hemodynamic response PSF by comparing these CBV-based signals with oxygen metabolism-based negative blood oxygenation level-dependent signals. A significant positive correlation exists between CBV- and metabolism-based iso-orientation maps, suggesting that the hemodynamic PSF is narrower than intercolumn distances. We also compared CBV-based fMRI with optical intrinsic signal (OIS) imaging, a technique that identifies sites of increased neuronal activity, to investigate neuronal correlation. Iso-orientation maps obtained by fMRI and OIS were well matched, indicating that areas of the highest orientation-selective CBV signals correspond to sites of increased neural activity. Using CBV-based fMRI, we successfully mapped orientation-selective functional architecture in the medial bank of the visual cortex, an area inaccessible to OIS imaging. Thus, we conclude that contrast agent-based fMRI, in combination with continuous temporally encoded stimulation, is a highly sensitive technique capable of mapping neural activity at the resolution of functional columns without depth limitation.

Animals↗
PubMed1982

Retinotopic and temporal organization of the optic nerve and tracts in the adult goldfish.

In order to investigate the role of the different factors controlling the pathways and termination sites of growing axons, selected optic fibers were traced from the eye to the tectum in adult goldfish either by filling them with HRP, or by severing a group of fibers and tracing their degeneration in 2 micrometers plastic sections stained with toluidine blue. Some fish received more than one lesion and others received both lesions and HRP applications. Two major rearrangements of the optic fibers were identified, one at the exit from the eye, the other within the optic tracts. Near the eye the optic fibers appear to be guided by the conformation of the underlying tissue planes that they encounter. The most recently added fibers, from the peripheral retina, grow over the vitread surface of the older fibers toward the blood vessel in the center of the optic nerve head. Behind the eye the fibers follow this blood vessel until it leaves the side of the optic nerve, and the fibers from peripheral retina are left as a single group on the ventral edge of the optic nerve cross section. As a consequence of this pattern of fiber growth the fibers form an orderly temporal sequence in the optic nerve, with the oldest fibers from the central retina on one side of the nerve and the youngest from peripheral retina on the other. In addition, the fibers are ordered topographically at right angles to this central-to-peripheral axis, with fibers from ventral retina on each edge of the nerve, dorsal fibers in the center, and nasal and temporal fibers in between. This arrangement of the optic fibers continues with only a little loss of precision up to the optic tracts. A more radical fiber rearrangement, seemingly incompatible with the fibers simply following tissue planes occurs within the optic tracts. Each newly arriving set of fibers grows over the surface of the optic tracts so that the older fibers come to lie deepest in the tracts. This segregation of fibers of different ages ensures that the rearrangement is limited to each layer of fibers. The abrupt reorganization of the fibers occurs as the tracts split around the nucleus rotundus to form the brachia of the optic tracts. The fibers are then arranged with temporal fibers nearest the nucleus rotundus and nasal fibers on the opposite edges of the brachia. From this point the fibers grow out over the tectal surface to their termination sites with only minimal rearrangements. Therefore the optic fiber rearrangements show evidence of several different sorts of constraints acting on the fibers at separate points in the optic pathway, each contributing to the final orderly arrangement of the fibers on the optic tectum.

Animals↗
PubMed2006

Electrical-contact-free readout of the response of superconductive bolometer arrays using thermal cross talk.

We utilized and investigated the unique dependence of the magnitude and phase of the response on thermal cross talk between bolometer pixels in an array to measure the response of the devices through fewer monitoring devices. We show the feasibility of the proposed readout technique by use of two source pixels in an array, as the image-mapping devices, and one optically shielded pixel as the readout device. While the sensing pixels were electrical-contact free, the readout device was current biased in 4-probe current-bias configuration. Both the phase and the magnitude of the response due to the cross talk in the array were found to be strongly dependent on the modulation frequency and the distance between the sensing and the readout pixels. A series of measurements were designed to extract the response of each single-sensing pixel. By combining the measured data, the response of individual pixels could be extracted through the interpolation of the mapped responses.

Journal Article↗
PubMed2005

Mapping of stimulus energy in primary visual cortex.

A recent optical imaging study of primary visual cortex (V1) by Basole, White, and Fitzpatrick demonstrated that maps of preferred orientation depend on the choice of stimuli used to measure them. These authors measured population responses expressed as a function of the optimal orientation of long drifting bars. They then varied bar length, direction, and speed and found that stimuli of a same orientation can elicit different population responses and stimuli with different orientation can elicit similar population responses. We asked whether these results can be explained from known properties of V1 receptive fields. We implemented an "energy model" where a receptive field integrates stimulus energy over a region of three-dimensional frequency space. The population of receptive fields defines a volume of visibility, which covers all orientations and a plausible range of spatial and temporal frequencies. This energy model correctly predicts the population response to bars of different length, direction, and speed and explains the observations made with optical imaging. The model also readily explains a related phenomenon, the appearance of motion streaks for fast-moving dots. We conclude that the energy model can be applied to activation maps of V1 and predicts phenomena that may otherwise appear to be surprising. These results indicate that maps obtained with optical imaging reflect the layout of neurons selective for stimulus energy, not for isolated stimulus features such as orientation, direction, and speed.

Animals↗
PubMed1992

The Critical Period for Experience-dependent Plasticity in a System of Binocular Visual Connections in Xenopus laevis: Its Temporal Profile and Relation to Normal Developmental Requirements.

A commissural system of 'intertectal' connections in Xenopus mediates the registration of binocular visual maps at the midbrain optic tectum. Following surgical eye rotation in larval animals, the system can completely alter its pattern of connectivity to restore binocular visual registration at the tectum. This experimentally induced plasticity is known to require visual experience and thought to be subject to an age-related restriction: eye rotation in adult animals is reported to provoke no subsequent intertectal alteration. In this paper we describe the detailed age-dependence of this plasticity. One eye was rotated in 238 animals of various developmental stages between mid-larval and adult life. At each age, different animals received rotations of different sizes, ranging from 20 to 180 degrees. The pattern of intertectal connectivity was mapped electrophysiologically 1 - 2 years postoperatively. A 'critical' period was defined around the time of metamorphosis: the vast majority of animals receiving a rotation in larval life (up to approximately 2 weeks before metamorphic climax) showed altered intertectal connections, whereas none of the animals operated upon at 3 months or more postmetamorphosis displayed the plasticity. At intervening ages, altered intertectal connections were found only in response to progressively smaller eye rotations. The profile of this critical period was further shown to mirror temporal features of the changes in eye position that occur in Xenopus as natural consequences of head growth, and which themselves impose a normal developmental requirement for intertectal plasticity. We conclude that the capacity of the Xenopus intertectal system for plasticity in response to abnormal experience undergoes a progressive age-dependent decline, and that the profile of this decline is delimited by normal requirements.

Journal Article↗
PubMed1989

Anterograde labelling from the optic nerve reveals multiple central targets in teleost, Lethrinus chrysostomus (Perciformes).

Cobaltous-lysine is transported anterogradely from the optic nerve of the teleost, Lethrinus chrysostomus (Lethrinidae, Perciformes). The marginal optic tract is labelled in longitudinal bands of light and dark staining fibres which persists caudally within the ventral division but not in the dorsal division. This species possesses multiple central targets in the contralateral preoptic, diencephalic, pretectal, periventricular and tectal regions of the brain. In addition, a greater subdivision of the marginal optic tract is found to project to various nuclei. Ipsilateral projections are found in the suprachiasmatic nucleus and in the region of the horizontal commissure. Projections are also found in the telencephalic region of the nucleus olfactoretinalis and the thalamic region of the nucleus thalamoretinalis. The retinotopicity of some of these nuclei, found in previous studies, is discussed in relation to the possibility of specific sub-populations of retinal ganglion cells having different central targets.

Animals↗
PubMed1982

An electrophysiological study of early retinotectal projection patterns during optic nerve regeneration in Hyla moorei.

The sequence of regeneration of the optic nerve into the tectum has been studied using electrophysiological visual mapping in the frog. Hyla moorei. Some individuals were remapped to confirm the sequential nature of the changes described. The projection was retinotopic throughout regeneration. Multiunit receptive field sizes were initially large but progressively decreased to normal over approximately 30 days. The differences between these results and earlier studies are discussed.

Animals↗
PubMed1998

Axon order in the visual pathway of the quokka wallaby.

Axon order throughout the visual pathway of the quokka wallaby (Setonix brachyurus) was determined after localised retinal applications of the tracers DiI and/or DiASP. Postnatal days (P) 22-90 were studied to encompass the development and refinement of retinal projections. Order was essentially similar at all stages. Axons entered the optic nerve head true to their sector of retinal origin. In the optic nerve, nasal and temporal axons continued to reflect their retinal origin, dominating, respectively, the medial and lateral halves. By contrast, dorsal and ventral axons exchanged locations between the retrobulbar level and one-third the distance along the nerve; thus, the inversion of the dorsoventral retinal axis, imposed by the lens, was corrected. Decussating axons maintained their relative locations through the chiasm. At the base of the optic tract, nasal and temporal axons underwent an axial rotation to lie on the medial and lateral sides, respectively; thus nasal overlapped with ventral axons and temporal with dorsal axons. Axons maintained their alignments throughout the tract, and as a result, nasal and ventral axons invaded the superior colliculus medially, whereas temporal and dorsal axons invaded laterally. Each retinal quadrant terminated preferentially in its retinotopically appropriate sector of the colliculus. The arrangement of axons in the quokka visual pathway displays several novel features. Axon order is distinct throughout, involving a well-demarcated exchange of dorsal and ventral axons in the nerve and an axial rotation of nasal and temporal axons at the base of the tract; these relocations suggest decision regions for growing axons. The organisation presumably underlies the less extensive searching within the developing superior colliculus to generate retinotopic maps in the quokka and also in tammar wallaby [Marotte, J. Comp Neurol. 293:524-539, 1990] than in the rat [Simon and O'Leary, J. Neurosci. 12:1212-1232, 1992].

Animals↗
PubMed2000

A site of auditory experience-dependent plasticity in the neural representation of auditory space in the barn owl's inferior colliculus.

The barn owl's optic tectum contains a map of auditory space that is based, in part, on a map of interaural time difference (ITD). Previous studies have shown that this ITD map is shaped by auditory experience. In this study, we investigated whether the plasticity responsible for experience-induced changes in ITD tuning in the tectum occurs within the tectum itself or at an earlier stage in the auditory pathway. We altered auditory experience in young owls by implanting an acoustic filtering device in one ear that caused frequency-dependent changes in sound timing and level. We analyzed the representation of ITD in normal and device-reared owls in two nuclei in the ascending pathway: the external nucleus of the inferior colliculus (ICX), the primary source of ascending auditory input to the tectum, and the lateral shell of the central nucleus of the inferior colliculus (ICCls), the primary source of input to the ICX. In the ICX, device rearing caused adaptive, frequency-dependent changes in ITD tuning, as well as changes in frequency tuning. These changes in tuning were similar to changes that occurred in the optic tectum in the same owls. In contrast, in the ICCls, tuning for ITD and frequency was unaffected by device rearing. The data indicate that plasticity at the level of the ICX is largely responsible for the adaptive adjustments in ITD tuning and frequency tuning that are observed in the optic tecta of owls raised with abnormal auditory experience.

Acoustic Stimulation↗