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PubMed1990

Cell recognition and pattern formation in the developing nervous system.

The topographic map of cell position in the avian retina is conserved and inverted when retinal ganglion neurons synapse with neurons in the optic tectum. Developmental mechanisms based on molecular gradients that specify positional information and pattern formation have been postulated in the establishment of these topographic maps of cells in retina and optic tectum. Two cell surface proteins in retina, TOP(DV) and TOP(AP), are distributed in dorsoventral and anteroposterior topographic gradients, respectively. Corresponding gradients of TOP molecules present in the tectum are inverted with respect to the retinal gradients. These orthogonal gradients of TOP(DV) and TOP(AP) molecules provide a possible Cartesian coordinate system for designation of cell position at all points in the retinotectal map.

Animals↗
PubMed1997

Application of rapid scanning retinal thickness analysis in retinal diseases.

PURPOSE: The authors have further developed their method of retinal thickness analysis to rapidly generate multiple optical cross sections of the retina and provide thickness maps at the posterior pole. The potential use of this method was evaluated in a number of macular disorders. METHODS: A commercial prototype of the scanning retinal thickness analyzer was used to examine patients with a variety of macular diseases. A laser slit beam was projected on the retina and scanned across a 2- X 2-mm retinal area in 200 to 400 msec. The images of the intersection of the laser slit beam with the retina were recorded digitally and used for visualization of disease. Nine scans were combined, and an operator-free algorithm generated a three-dimensional thickness map at the posterior pole. RESULTS: Cysts could be visualized in macular edema associated with diabetes mellitus and with retinal vein occlusion. The retinal thickness map quantitated the location, extent, and height of the edema. In serous detachment, the extent and the height of the retinal pigment epithelial elevation could be documented. In cases of suspected macular holes and pseudoholes, the diagnosis was considered more reliable than with conventional biomicroscopy. The extent of epiretinal membranes, the sites of adherence, and associated intraretinal cystic changes were identified. In glaucoma, the anatomic course of localized loss of neuronal retinal tissue could be traced. CONCLUSIONS: Scanning retinal thickness analysis provided multiple optical cross sections of the retina and yielded information useful in the diagnosis and monitoring of macular diseases. The three-dimensional thickness map provided quantitative information that may be useful for clinical management.

Anatomy, Cross-Sectional↗
PubMed1980

Retention of topographic addresses by reciprocally translocated tectal re-implants in adult goldfish.

1. The topographic pattern of retinotectal projections re-established after reciprocal translocation of two tectal re-implants within a whole tectum was studied in adult goldfish with neurophysiological mapping methods. 2. Reciprocal translocations of tectal re-implants along the rostrocaudal axis resulted in retinotectal projections on to these re-implants that showed corresponding reciprocal transpositions of receptive fields along the nasotemporal axis. 3. Similarly, reciprocal translocations of tectal re-implants along the mediolateral axis resulted in retinotectal projections on to these re-implants that showed corresponding reciprocal transpositions of receptive fields along the superoinferior axis. Some regenerating optic fibres in the operated tectum abruptly changed the directions of their courses, as if they were taking direct paths towards their displaced, previous target zones in the tectum. 4. Reciprocal translocation of tectal re-implants either along the rostrocaudal or mediolateral axis, accompanied by 180 degree rotation of the re-implants about the dorsoventral axis, resulted in retinotectal projections on to the re-implants that showed not only the corresponding reciprocal transpositions along the nasotemporal or superoinferior axis but also a localized 180 degree rotation in the order of the receptive fields within these re-implants. The same results were also observed after regeneration of the optic fibres following section of the contralateral optic nerve. 5. These results indicate that translocated pieces of tectal tissue retain not only the topographic polarity indicative of their normal orientation but also the topographic addresses indicative of their original positions in the tectum, with respect to their selective reinnervation by particular groups of optic fibres.

Animals↗
PubMed1982

Retinotopic organization of lateral eye input to Limulus brain.

1. The retinotopic organization of retinal inputs from the lateral eye of Limulus to the optic ganglia of the brain was determined from microelectrode recordings of nerve impulses. 2. The central connections of the natural subunits of the lateral optic nerve were determined using cobalt impregnation of cut axons. 3. Complete retinal maps exist in both the lamina and medulla. The laminar map is a simple rotation and folding of the retinal array. The medullar map is more complex as a result of the combined effects of the chiasma and the basic subunit structure of the optic nerve, which is preserved in the lamina and medulla. 4. The chiasma between the lamina and medulla reverses the anterior-posterior axis of the retinal map. There is no corresponding reversal in the dorsal-ventral axis.

Animals↗
PubMed2002

Correspondence between odorant-evoked patterns of receptor neuron input and intrinsic optical signals in the mouse olfactory bulb.

We compared odorant-evoked patterns of receptor neuron input to the mouse olfactory bulb, imaged with a calcium-sensitive dye, with those of intrinsic optical signals imaged from the same preparations. Both methods yielded patterns of glomerular activity that showed a strong concentration dependence, a loosely organized chemotopy, and involved widely distributed glomeruli. Presynaptic calcium and intrinsic signals showed similar odorant concentration thresholds. Intrinsic signal foci were larger than their corresponding calcium signals, and input to multiple adjacent glomeruli often appeared as a single intrinsic focus. Nonetheless, at near-threshold concentrations, the correspondence between the glomerular calcium and intrinsic signals averaged 75%, with a 71% correspondence between the most strongly activated glomeruli. The correspondence between strongly activated glomeruli decreased as odorant concentration increased, dropping to 51% at 5- to 15-fold higher concentrations. Intrinsic signal foci often saturated at lower concentrations than the calcium signal, implying a smaller dynamic range, and suprathreshold concentrations could recruit strong intrinsic signals in areas showing little or no calcium signal. These differences were such that, at suprathreshold concentrations, the chemotopy of calcium and intrinsic signal response maps often differed. These results suggest that intrinsic optical signals closely reflect receptor neuron input to glomeruli at low odorant concentrations but reflect additional processes at higher concentrations (activation of second-order neurons, centrifugal input, or constraints on the coupling between neuronal activity and hemodynamic changes). Intrinsic signals that are not associated with receptor neuron input have the potential to impact the interpretation of spatial coding strategies in the olfactory bulb.

Animals↗
PubMed2004

Congenital abnormalities of cranial nerve development: overview, molecular mechanisms, and further evidence of heterogeneity and complexity of syndromes with congenital limitation of eye movements.

PURPOSE: The clinical and molecular genetic classification of syndromes with congenital limitation of eye movements and evidence of cranial nerve dysgenesis continues to evolve. This monograph details clinical and molecular genetic data on a number of families and isolated patients with congenital fibrosis of the extraocular muscles (CFEOM) and related disorders, and presents an overview of the mechanisms of abnormal patterns of motor and sensory cranial nerve development in these rare syndromes. METHODS: Clinical examination of one patient with CFEOM1, one family with clinical features of CFEOM2, one family with recessive CFEOM3, one family with horizontal gaze palsy and progressive scoliosis (HGPPS), and four patients with various combinations of congenital cranial nerve abnormalities. Genotyping of families with CFEOM and HGPPS for polymorphic markers in the regions of the three known CFEOM loci and in the HGPPS region, and mutation analysis of the ARIX and KIF21A genes in patients with CFEOM were performed according to standard published protocols. RESULTS: The patient with CFEOM1 had the second most common mutation in KIF21A, a 2861 G>A mutation that resulted in an R954Q substitution. The family with CFEOM2 phenotype did not map to the CFEOM2 locus. The family with recessive CFEOM3 did not map to any of the known loci. The HGPPS family mapped to 11q23-q25. One patient had optic nerve hypoplasia and fifth nerve dysfunction. Two patients had the rare combination of Möbius syndrome and CFEOM. One patient had Möbius syndrome and fifth nerve dysfunction. CONCLUSIONS: There is genetic heterogeneity in CFEOM2 and CFEOM3. Abnormalities in sensory nerves can also accompany abnormalities of motor nerves, further substantiating the effect of individual mutations on developing motor as well as sensory cranial nerve nuclei.

Adenine↗
PubMed1990

Ipsilateral retinofugal projections in a percomorph bony fish: their experimental induction, specificity and maintenance.

Adult bony fish possess only a small ipsilateral retinofugal projection, if any. Experimental manipulation, such as unilateral enucleation, can lead to an enhancement of this projection. We examined the patterns of, as well as the conditions for the development and maintenance of an enhanced ipsilateral retinofugal projection (EIRP) after nerve crush, after enucleation, and after various combinations of both types of surgery in juvenile and adult Haplochromis burtoni (Cichlidae). Retinal projections were labeled either unilaterally with horseradish perixodase, or with the lipophilic fluorescent dye DiI in aldehyde-fixed animals, or bilaterally with differently colored fluorescent dextran amines. Unilateral nerve crush always leads to the regeneration of retinofugal fibers to the contralateral tectum but spares some contralateral diencephalic nuclei. In addition, unilateral or bilateral nerve crush in many cases, and unilateral enucleation in some cases, leads to the development of an EIRP to the ipsilateral diencephalon and tectum. This EIRP persists (4 months and longer postoperatively) in only 10% of the unilaterally enucleated animals, in none of the animals subjected to unilateral nerve crush and in 79% of the animals subjected to bilateral nerve crush. All unilaterally enucleated animals in which the remaining, contralateral optic nerve was crushed develop and maintain an EIRP. These data suggest that nerve crush alone is sufficient to cause regenerating fibers to project, at least transiently, to the ipsilateral side of the brain. When the normal contralateral projection is either absent or in the process of regeneration, an EIRP can be maintained. In the latter case, alternate bands or patches of ipsi- and contralateral fibers in the tectum may result. Ipsilateral fibers follow unusual pathways by recrossing at the rostral diencephalon. Likewise, regenerating contralateral retinal fibers grow differently in this area; here, where the optic-nerve projection is reorganized into the optic tract, many regenerating fibers are deflected to the ipsilateral side of the brain. Despite atypical routes taken by some fibers, the EIRP nevertheless ends only in specific retinorecipient areas. An EIRP develops independently of the age of the animal, independently of the time lapse between enucleation and nerve lesion, and independently of persisting debris. However, in animals receiving an optic nerve lesion a long time after unilateral enucleation, the size of the EIRP and its tectal extent are reduced compared to that in animals enucleated around the same time as receiving the crush of the contralateral optic nerve.

Animals↗
PubMed2005

A system for real-time XMR guided cardiovascular intervention.

The hybrid magnetic resonance (MR)/X-ray suite (XMR) is a recently introduced imaging solution that provides new possibilities for guidance of cardiovascular catheterization procedures. We have previously described and validated a technique based on optical tracking to register MR and X-ray images obtained from the sliding table XMR configuration. The aim of our recent work was to extend our technique by providing an improved calibration stage, real-time guidance during cardiovascular catheterization procedures, and further off-line analysis for mapping cardiac electrical data to patient anatomy. Specially designed optical trackers and a dedicated calibration object have resulted in a single calibration step that can be efficiently checked and updated before each procedure. An X-ray distortion model has been implemented that allows for distortion correction for arbitrary c-arm orientations. During procedures, the guidance system provides a real-time combined MR/X-ray image display consisting of live X-ray images with registered recently acquired MR derived anatomy. It is also possible to reconstruct the location of catheters seen during X-ray imaging in the MR derived patient anatomy. We have applied our registration technique to 13 cardiovascular catheterization procedures. Our system has been used for the real-time guidance of ten radiofrequency ablations and one aortic stent implantation. We demonstrate the real-time guidance using two exemplar cases. In a further two cases we show how off-line analysis of registered image data, acquired during electrophysiology study procedures, has been used to map cardiac electrical measurements to patient anatomy for two different types of mapping catheters. The cardiologists that have used the guidance system suggest that real-time XMR guidance could have substantial value in difficult interventional and electrophysiological procedures, potentially reducing procedure time and delivered radiation dose. Also, the ability to map measured electrical data to patient specific anatomy provides improved visualization and a path to investigation of cardiac electromechanical models.

Cardiac Catheterization↗
PubMed2004

Pax6 interacts with cVax and Tbx5 to establish the dorsoventral boundary of the developing eye.

Dorsoventral pattern formation of the optic cup is essential for vertebrate eye morphogenesis and retinotectal topographic mapping. Dorsal and ventral aspects of the eye are distinct at early stages of development; cVax homeodomain protein expression is confined to the ventral optic cup, whereas Tbx5 (T-box transcription factor) expression domain becomes restricted to the dorsal region. Misexpression of cVax or Tbx5 induces profound defects in eye morphology and abnormal visual projections. In the Pax6-/- mutant Tbx5 fails to be expressed, and Vax1 and -2 are abnormally present in the entire optic vesicle. During eye development Pax6 becomes expressed in a gradient at the optic cup stage due to the specific activation of a highly conserved intronic alpha enhancer in the Pax6 locus. We observed that the highest level of Pax6 in the optic cup corresponds to the boundary between non-overlapping cVax and Tbx5 territories. To further investigate how these transcription factors control the patterning of the eye, we overexpressed Pax6 in the chick optic cup (E2) using in ovo electroporation. We observed that overexpression of Pax6 extends the Tbx5 and Bmp4 domains but reduces the cVax expression domains in the E3 chick eye. This results in an abnormal eye phenotype at E4. In addition, we showed that cVax and Tbx5 interact with Pax6 and modulate in an opposite manner the activity of the Pax6 alpha enhancer. Moreover, the Pax6/cVax interaction inhibits the transactivation properties of Pax6. These results demonstrate that Pax6 together with cVax and Tbx5 mediate dorsoventral patterning of the eye.

Animals↗
PubMed1983

Crossed and uncrossed visual topography in dorsal lateral geniculate nucleus of the pigmented rat.

1. The representation of the retinocentric visual field within the dorsal lateral geniculate nucleus (dLGN) was assessed electrophysiologically by recording multicellular responses from anesthetized pigmented rats. Separate experiments examined the representation through either the contralateral or ipsilateral eye along the dorsoventral, mediolateral, and rostrocaudal dimensions of the nucleus. 2. The crossed projection displays an orderly representation of the visual field, mapping eccentricities out to 100 degrees from the optic disk. There is, however, a marked absence of eccentricities greater than 60 degrees representing upper nasal visual space. The uncrossed projection also displays an orderly representation of the visual field but is limited in extent to upper nasal visual space at far eccentricities of 50-90 degrees. 3. The ipsilateral projection, which represents far eccentric upper nasal visual space, occupies a region in the contralateral representation corresponding with upper nasal visual space at reduced eccentricity. It is these two regions that are considered binocularly conjugate: the temporal crescent of each eye with another crescent (the conjugate central crescent) lying between the optic disk and the temporal crescent of the opposite eye. It is suggested that the crossed and uncrossed representations are aligned in the dLGN so that projection lines for discrete regions of the binocular visual field course through the nucleus from rostroventral to caudodorsal. Although the dLGN of the rat lacks the cytoarchitecturally distinct laminae associated with the regions of afferent input from each eye, as is seen in the primate and cat dLGN, the organizing principle of apposing the representation of the visual field through each eye is similar.

Animals↗
PubMed1981

Retinal projection in a non-visual area after bilateral tectal ablation in goldfish.

If, in the adult goldfish, one optic tectum is ablated, the regenerating optic axons from the contralateral retina innervate the remaining tectum, where they form a retinotopically ordered map. The pathway for this induced ipsilateral projection coincides with many of the pathways which normally connect the two tecta, but early in regeneration the optic fibres also enter non-visual centres to which there are degenerating tectal efferent pathways to follow. We have therefore now investigated the fate of regenerating optic axons in goldfish from which both optic tecta have been removed; they are found to innervate non-visual centres, where again they generate a retinotopic map.

Animals↗
PubMed2003

Grouping of odorant receptors: odour maps in the mammalian olfactory bulb.

The olfactory system is unique in that the sensory input is in the form of molecular information carried in a vast variety of odorants. Nearly 1000 types of odorant receptors mediate the initial detection and discrimination of odorants at the molecular-feature level. The discrimination at the molecular level is converted into that at the cellular level (olfactory sensory neurons) by the one sensory neuron-one odorant receptor rule, and then into that at the neuronal circuit level in the olfactory bulb by the specific olfactory axon connectivity pattern. Individual glomeruli in the olfactory bulb represent a single odorant receptor, and the glomerular sheet at the olfactory bulb surface forms odorant receptor maps. This review focuses on the spatial organization of the glomerular sensory map in the olfactory bulb. The analysis using the optical imaging method suggests that odorant receptors having a common molecular-feature receptive site are grouped together and represented by glomeruli that are localized in topographically fixed domains in the olfactory bulb. The domain organization may be a structural unit for the spatial organization of the glomerular sensory map, and might relate to the olfactory submodality.

Animals↗
PubMed1995

Initial assessment of a simple system for frequency domain diffuse optical tomography.

Diffuse optical tomography is an imaging technique whereby spatial maps of absorption and scattering coefficients are derived from the characteristics of multiply scattered light transmitted through the object. The system described here used four intensity-modulated light sources and measurements of the intensity and phase (relative to each source) at 16 or 20 detectors on the surface of a 10 cm diameter cylinder. An iterative Newton-Raphson algorithm was used to estimate the absorption and scattering coefficients at each pixel in a 17 x 17 array minimizing the difference between measured and calculated values of the intensity and phase at the measurement sites. Forward calculations of the intensity and phase were based on a multigrid finite-difference solution of the frequency domain diffusion equation. Numerical simulations were used to examine the resolution, contrast, and accuracy of the reconstructions as well as the effects of measurement noise, systematic uncertainties in source-detector location, and accuracy of the initial estimates for the optical properties. Experimental tests also confirmed that the system could identify and locate both scattering and absorbing inhomogeneities in a tissue-simulating phantom.

Algorithms↗
PubMed1984

The mormyrid mesencephalon. III. Retinal projections in a weakly electric fish, Gnathonemus petersii.

The optic nerve and the retinal projections were studied in a mormyrid fish, Gnathonemus petersii, by using Fink-Heimer, HRP, cobalt labeling, and autoradiographic tracing techniques. The retinal fibers terminate bilaterally in the following places: suprachiasmatic nucleus, dorsolateral optic nucleus, optic nucleus of the posterior commissure, cortical nucleus, ventral pretectal area, optic tectum, and the accessory optic terminal field. The number of uncrossed fibers is relatively high in the suprachiasmatic nucleus, but negligibly small in the other retinal terminal fields. In the lateral geniculate nucleus and pretectal nucleus only crossed retinal fibers could be detected. The visual system of Gnathonemus is compared to that of other fishes, amphibians, and reptiles and the possible homologies are proposed. The comparison points to the conclusion that the visual system is less developed in Gnathonemus. This nocturnal species lives in turbid waters and has a special electric sense which may permit compensation for the reduced visual capacity.

Animals↗
PubMed2000

Mapping the air in real-time to visualize the flow of gases and vapors: occupational and environmental applications.

This article describes a new method for measuring and mapping pollutants in air in real-time which can be used for visualizing the flow of gases and vapors in both indoor industrial and outdoor environmental applications. This method uses open-path Fourier Transform Infrared (OP-FTIR) spectrometry and computed tomography for real-time mapping of concentrations of chemicals in air. These maps may be used to evaluate human exposures, source emissions and air dispersion models; thus, this method can be used for both industrial and environmental sampling. It is being developed using computer simulations, and chamber and field studies. Computer simulations used simulated test concentration data to create maps; the original maps of concentrations were compared with the tomographic reconstructed maps. In the chamber studies, tracer gas was released into the chamber and measurements from a tomographic system were compared with point sample measurements taken at the same time. When sulfur hexafluoride was injected in a stable flow field position in the chamber, the concentrations reconstructed by the concentration maps were within +/- 15.9 percent of the measured point samples; overall, they were within +/- 27 percent of the measured point samples. On a 12-foot by 14-foot grid of cells used to model the chamber, the average peak location error was within one foot. The peak location error refers to the error involved in locating the point of highest concentration in the plume. For the field study, field-generated tomographic maps were compared with concentrations estimated using the Industrial Source Complex-Short Term (ISCST) model. Fairly good correlation (R2 = 0.67) was found between the five-minute overall-average cell concentrations in the tomographic and ISCST model maps. Overall, the tomographic map concentrations over-predicted the ISCST model concentrations by 24 percent. Optical remote sensing and computed tomography shows promise as a method to produce spatially and temporally resolved two-dimensional concentration maps indoors and outdoors. These maps would provide near real-time visualization of contaminant generation, movement, concentrations, and emission rates for multiple chemicals simultaneously at low limits of detection.

Air Pollution↗
PubMed1991

Tectectomy in the cyclopean salamander.

In an Ambystoma larva with both natural eyes removed and one eye grafted atop the head (Cyclops preparation), vision-dependent behavior usually recovers from the enucleation inherent in the operation, but the optically activated skin blanching reaction reappears in a very small number of instances. In the present studies, while the latter trend continued for the conventional Cyclops preparation, tectectomy concurrent with the ectopic eye transplantation resulted in a several-fold increase in the recovery of blanching competency. Some 60 percent of the tectectomized Cyclops animals exhibited the same Hogben-Slome pigmentation indices as larvae with one natural eye intact (controls). As measured planimetrically with an image analyzer, the pigment spots (melanosome containing portions of dermal melanocytes) contracted to the same extent in the blanch-competent Cyclops animals as in controls with a single natural eye.

Ambystoma↗