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Analysis of mouse EphA knockins and knockouts suggests that retinal axons programme target cells to form ordered retinotopic maps.

I present a novel analysis of abnormal retinocollicular maps in mice in which the distribution of EphA receptors over the retina has been modified by knockin and/or knockout of these receptor types. My analysis shows that in all these cases, whereas the maps themselves are discontinuous, the graded distribution of EphA over the nasotemporal axis of the retina is recreated within the pattern of axonal terminations across rostrocaudal colliculus. This suggests that the guiding principle behind the formation of ordered maps of nerve connections between vertebrate retina and superior colliculus, or optic tectum, is that axons carrying similar amounts of Eph receptor terminate near to one another on the target structure. I show how the previously proposed marker induction model embodies this principle and predicts these results. I then describe a new version of the model in which the properties of the markers, or labels, are based on those of the Eph receptors and their associated ligands, the ephrins. I present new simulation results, showing the development of maps between two-dimensional structures, exploring the role of counter-gradients of labels across the target and confirming that the model reproduces the retinocollicular maps found in EphA knockin/knockout mice. I predict that abnormal distributions of label within the retina lead to abnormal distributions of label over the target, so that in each of the types of knockin/knockout mice analysed, there will be a different distribution of labels over the target structure. This mechanism could be responsible for the flexibility with which neurons reorganise their connections during development and the degree of precision in the final map. Activity-based mechanisms would play a role only at a later stage of development to remove the overlap between individual retinal projection fields, such as in the development of patterns of ocular dominance stripes.

Animals↗

Differential effects of ocular BDNF-injections onto the development of tectal cells characterized by calcium-binding proteins in pigeons.

The optic tectum of vertebrates bears a set of visual neurons which can be differentiated by the expression of distinct calcium-binding proteins (CaBPs). Using immunohistochemistry, we mapped the distribution of the CaBPs calbindin (CB) and parvalbumin (PV) in the pigeon's optic tectum and examined if their differentiation is affected by retinal brain-derived neurotrophic factor (BDNF)-injections. CB-immunoreactive (ir) and PV-ir cells displayed a lamination pattern which differed from other birds. While PV-ir cells were present in several retinorecipient tectal laminae, CB-ir cells were confined to layer 3 and 5 and - as a specialization of pigeons - were also detected in a subpopulation of layer 13 neurons. Comparison of saline- and BDNF-injected animals revealed that this general expression pattern was not affected by ocular BDNF-injections. In contrast, the size of tectal cells was differentially modulated. While CB-ir cells in layers 3 and 13 were unaffected by retinal BDNF, cells in layer 5 developed enlarged cell bodies. The PV-ir cells displayed smaller soma sizes within both tectal hemispheres suggesting also an indirect effect of retinal BDNF. These data indicate a differential sensitivity of tectal cell types to retinal BDNF, which might be one mechanism by which retinal input modulates tectal circuitries.

Animals↗

The pretectal complex in the opossum: projections from the striate cortex and correlation with retinal terminal fields.

Two terminal fields were revealed in the pretectal complex of the opossum by the Fink-Heimer method after striate cortical lesions. A rostral field is located within a rostrolateral strip of the compact part of the anterior pretectal nucleus, where a partial topographic arrangement of this projection is present. A caudal field is located within the sub-brachial nucleus of the optic tract, located between the brachium of the superior colliculus and the posterior pretectal nucleus. The corticotopic projection to this field is mirror-symmetric to that found in the superior colliculus and overlaps a bilateral projection from the retina. Based on neural pathway evidence, it is concluded that the nucleus of the optic tract in the opossum can be subdivided in (a) an intrabrachial nucleus receiving a direct projection from the contralateral retina and (b) a sub-brachial nucleus receiving projections from both retinae and from the striate cortex. The pretectal complex, as the superior colliculus, can be anatomically subdivided in a superficial region receiving visual input (the optic pretectum) and a deep region only remotely connected to the visual system. The optic pretectum, however, differs from the superior colliculus in displaying a multiple-map arrangement within its constituent nuclei, instead of a single continuous representation of the visual field.

Animals↗

Quantitative phase-contrast imaging of cells with phase-sensitive optical coherence microscopy.

We describe a method for en face phase-contrast imaging of cells with a fiber-based differential phase-contrast optical coherence microscopy system. Recorded en face images are quantitative phase-contrast maps of cells due to spatial variation of the refractive index and (or) thickness of various cellular components. Quantitative phase-contrast images of human epithelial cheek cells obtained with the fiber-based differential phase-contrast optical coherence microscopy system are presented.

Cheek↗

Quantitative point source photoacoustic inversion formulas for scattering and absorbing media.

We present here an expression for the photoacoustic contribution of an optical point source in a diffusive and absorbing medium. By using this measurement as a reference, we present a direct inversion formula that recovers the absorption map quantitatively, at the same time accounting for instrumental factors such as the source strength, the shape of the optical pulse, and the impulse response and finite size of the transducers. We further validate this expression through accurate numerical simulations showing that the absorption map is recovered quantitatively in the presence of a rotating geometry. We finally discuss how the presented solutions for point sources within the photoacoustic problem enable the use of concurrent fluorescence and ultrasound measurements as appropriate for a hybrid tomographic system. The proposed system could retrieve absorption information using photoacoustic measurements, and use these data to more accurately describe the fluorescence problem and improve reconstruction fidelity.

Absorption↗

Histological evidence for direct connections between the optic lobes of the cockroach Leucophaea maderae.

Heretofore, descriptions of direct interconnections between insect optic lobes have been based on histological examinations of normal brains or on inference from electrophysiological or behavioral data. We present here what we believe to be the first demonstration of such monosynaptic connections by techniques of experimental neuroanatomy. Twenty-four to 39 h after extirpation of the left optic lobe, degenerating axons and axon terminals, as silvered by a modified Nauta technique, were abundant in the central portion of the medulla of the right optic lobe. The periphery of the medulla was free of argyrophilic debris as were the lobula and lamina. The distribution of neuronal somata with processes terminating in the the left optic lobe was established by retrograde axonal transport of horseradish peroxidase injected into the left lobe and by the development of distinctive perinuclear rings of RNA (a 'chromatolytic' reaction) by some cells within 1-2 weeks following amputation of the left lobe. Both techniques revealed distinct clusters of cells in the anteroventral and posterior regions of the right optic lobe, and in the medial portion of the right protocerebrum. The cells which interconnect the two optic lobes may be involved not only in the bilateral representation of visual information, but also in the coordination of optic lobe pacemakers which control a circadian rhythm of locomotory activity.

Animals↗

[Visual projections into the telencephalon and diencephalon of the teleost fish Serranus scriba (electrophysiologic study)].

In acute experiments on Serranus scriba, two discrete foci of visual activity in the telencephalon were shown--in the dorsal pallium and in the central telencephalic area. The latency of focal potentials evoked by optic tectum stimulation was at least 2 msec shorter than that of the responses elicited by optic nerve stimulation. In the region of nucleus rotundus and some other thalamo-pretectal structures, focal potentials and single unit reactions to both types of stimulation were registered. Responses to optic tectum stimulation in nucleus pretectalis exhibited the shortest latency. It is suggested that visual impulses to the central telencephalic area are relayed consequently in the optic tectum and probably in more than one thalamo-pretectal nucleus.

Animals↗

Global and regional detection of induced optic disc change by digitized image analysis.

OBJECTIVE: To evaluate two new strategies for the detection of optic disc change within individual eyes by digitized image analysis. METHODS: Eleven normal optic discs of 11 monkeys were imaged with a digital imaging system (Topcon Imagenet, Topcon Instrument Corporation of America, Paramus, NJ) at two intraocular pressures (10 and 45 mm Hg). To detect global change in the disc, we compared conventional optic disc parameters with a new optic disc parameter: mean position of the disc. To detect regional change, the 95% confidence interval for change was calculated for each data point and mapped for each disc. RESULTS: Posterior deformation of the disc surface was detected in seven of 11 eyes using conventional parameters and in 10 of 11 eyes using mean position of the disc. Regions of posterior deformation were detected by 95% confidence interval for change mapping in all 11 discs as localized areas of confluent, posteriorly displaced points. CONCLUSIONS: Mean position of the disc outperformed conventional measurements in the detection of global optic disc change. Ninety-five percent confidence interval for change mapping may allow individual data point-based focal and regional analysis of the disc.

Animals↗

A chamber and artificial dura method for long-term optical imaging in the monkey.

Optical imaging over extended periods of time in non-human primates presents serious challenges because the dura mater must be removed to expose the cortical surface. We present a novel nylon imaging chamber with a transparent artificial dura implant, which allows repeated, long-term optical recordings from the cortex. The cylinder of the chamber is inserted into a cranial trephination and held in place with a minimum of screws and acrylic cement. A round patch of artificial dura with a perpendicular wall protects the cortical surface and slows re-growth of dural tissue within the chamber. A cap, manufactured from the same material as the cylinder, is screwed into the chamber and seals it completely. Over a period of 1-4 months, the chamber required a minimum of maintenance and stayed infection-free without local antibiotic application. We repeatedly performed optical imaging in the same animal with the advantages of shortened preparation time. To permit precise alignment and comparison of maps obtained from different imaging sessions, we developed a program that calculated a 2-dimensional spatial transformation between maps of different magnifications, translations, and distortions. We suggest that these methods provide a practical solution to long-term optical imaging in the anesthetized or alert monkey. The exclusive use of non-metallic materials offers the benefit of a lighter and more compact implant, and the possibility to perform MRI scans after chamber implantation.

Anesthesia↗

Measurement of retinal thickness in normal subjects with retinal thickness analyzer.

The retinal thickness at posterior pole of normal subjects was measured by using retinal thickness analyzer (RTA) to determine the values of retinal thickness and to establish map of retinal thickness in normal subjects. The retina of 6 mm x 6 mm in size (approximately 20 degrees, centered on the macula) at the posterior pole was scanned by using RTA to obtain images of 116 normal eyes of 77 cases of various age group. The images were processed by a computer to obtain the retinal thickness values and the thickness map of this location. The data were analyzed with SAS software package. The mean retinal thickness was 171.77 +/- 26.13 microns with no significant difference among the various age groups (P > 0.05). The thickness maps of the retina of 6 mm x 6 mm size at the posterior pole around the macula rendered a "U"-shaped pattern, extending from the disc to the superior and inferior of the fovea. The retina was found to be thin at temporal side of the fovea, with the thinnest area being at the macula central fovea. The U-shaped pattern of the retinal thickness maps was well in agreement with the topography of the ganglion cells and the retinal nerve fibers in human retina. The measurement of the retinal thickness by RTA reflected the changes in the layers of ganglion cells and the retinal nerve fiber. Each scanning session of RTA examination can yield multiple optical cross-section images of the retina and obtain retinal thickness maps of posterior pole of living eyes.

Humans↗

The diencephalon of the channel catfish, Ictalurus punctatus. II. Retinal, tectal, cerebellar and telencephalic connections.

In a companion paper, the nuclear organization of the diencephalon of the channel catfish, Ictalurus punctatus, was described and compared to that of other teleosts. The present paper describes the connections of the diencephalon with the retina, optic tectum, corpus of the cerebellum and telencephalon. The principal tracer employed is the indocarbocyanine dye DiI which diffuses along neuronal membranes in fixed tissues. Almost all of the nuclei that were recognized as distinct in the companion study are found to also exhibit distinct sets of connections. Most of these connections have not been described previously in catfishes or other teleosts. When combined with connectional data from the existing literature, the results of the present study allow one to recognize a great number of distinct pathways through the diencephalon of channel catfish, including several visual, auditory, gustatory, electrosensory and mechanosensory pathways to the telencephalon. Almost all of the species differences in diencephalic organization noted in the companion study can be accounted for by changes in one of the major sensory pathways. In contrast, the multimodal and integrative areas of the diencephalon appear to be relatively conservative. A comparison between the diencephalon of teleosts and that of other vertebrates suggests that the dorsal thalamus, the ventral thalamus and the posterior tuberculum are homologous, at least in part, to the dorsal thalamus, the zona incerta and the subthalamic nucleus of mammals, respectively. All three areas project to the telencephalon in both mammals and teleosts. In most vertebrates, however, the dorsal thalamus provides the dominant input to the telencephalon, whereas in teleosts the main telencephalic input derives instead from the posterior tuberculum.

Animals↗

Mapping of the retinal pigment epithelium in exudative age related macular degeneration.

PURPOSE: To evaluate a novel technique for three-dimensional mapping of the retinal pigment epithelium (RPE) layer in patients with subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration. METHODS: Scanning with a recent generation retinal thickness analyzer (RTA) was performed in consecutive patients undergoing fluorescein angiography. From a 3 x 3 mm area centered on the fovea, three-dimensional area maps of the RPE level were calculated by external spreadsheet software. Included were 18 eyes with classic CNV, 18 eyes with occult CNV and 18 eyes from age-matched normal subjects. Repeatability was assessed by measuring 17 eyes with CNV 3 times. In ten additional patients, RTA imaging results were compared with cross-sections obtained by optical coherence tomography. RESULTS: By both methods, distinctive changes in RPE level maps were observed in classic and occult CNV. In classic CNV with the lesion extending over the RPE, only focal irregularities in the anteriorly displaced RPE surface were observed. In contrast, mapping of occult CNV showed a more irregular displacement of the RPE layer. The RPE map standard deviation indicating surface irregularity differed statistically significantly between the groups, with coefficients of variance of 5.9% for controls, 6.1% for classic and 8.8% for occult CNV (P < 0.001). Regarding repeatability, RPE level maps showed 1.2% coefficient of variance and an intra-class correlation coefficient of 0.87 for triplicate measurements in CNV patients. CONCLUSIONS: Topographic mapping of CNV lesions offers a fast, reproducible method for obtaining three-dimensional morphometric information on the RPE level and to quantify changes.

Adult↗

Mapping of the water quality of Lake Erken, Sweden, from imaging spectrometry and Landsat Thematic Mapper.

Hyperspectral data have been collected by the Compact Airborne Spectrographic Imager (CASI) and multispectral data by the Landsat Thematic Mapper (TM) instrument for the purpose of mapping lake water quality. Field campaigns have been performed on Lake Erken in Sweden during the summer of 1997. Water samples have been collected and analysed in laboratory. Continuously measured variables from a boat have added a spatial dimension to the ground truth dataset. The data have been used to construct algorithms, based on remotely sensed data, for the retrieval of water quality parameters. The correlation between the continuous data and the collected CASI data has been investigated. Algorithms using both the point sampling results and the continuous data have been developed. Maps based on data from each instrument, showing the distribution of chlorophyll, are presented. Problems of having few water sampling stations, and the potential of using sub-water optics models are addressed as well. Tests were performed on MERIS bands and found useful for mapping chlorophyll and turbidity, and algorithms have been suggested for future use with MERIS.

Algorithms↗

Infantile bilateral striatal necrosis maps to chromosome 19q.

BACKGROUND: Infantile bilateral striatal necrosis (IBSN) encompasses several syndromes of bilateral symmetric degeneration of the caudate nucleus, putamen, and globus pallidus. Autosomal recessive IBSN is characterized clinically by developmental arrest beginning at age 7 to 15 months, dysphagia, choreoathetosis, pendular nystagmus and optic atrophy, and severe progressive atrophy of the basal ganglia on MRI. OBJECTIVE: To map the gene causing IBSN. METHODS: A 10-cM genome-wide linkage scan was initially performed on five affected and five unaffected individuals. The extended family was included in the analysis to narrow the candidate region. Logarithm of odds (LOD) score was calculated using the SUPERLINK program. RESULTS: Linkage to the chromosomal region 19q13.32-13.41 was established (Z(max) = 6.27 at theta = 0.02 at locus D19S412). Recombination events and a common disease-bearing haplotype defined a critical region of 1.2 Mb between the loci D19S596 proximally and D19S867 distally. CONCLUSION: IBSN maps to the chromosomal region 19q13.32-13.41. The presence of a common haplotype in all the patients suggests that the disease is caused by a single mutation derived from a single ancestral founder in all the families.

Age of Onset↗

Evaluation of four blood pump geometries: the optical tracer technique.

Artificial blood pump assistance of the failing human heart can allow it to recover. Analysis of blood pump fluid flow is a useful tool for design development and thrombosis minimization. The aim of this study was to investigate fluid flow, particularly ventricular clearance rate and stagnation areas, in four different blood pump geometries and to determine the best design. The blood pumps consisted of a polyurethane ventricle, and combinations of inlet/outlet pipe angles and compression plate shapes. A video camera recorded the motion of fluid labelled with an optical tracer (Methyl Blue histological dye). A novel processing method was developed to produce colour maps of tracer concentration, experimentally calibrated. An overall picture of fluid flow in each pump geometry was generated by considering clearance curves, tracer concentration maps and inflow jet animations. Overall and local mixing coefficients are calculated for each pump. The best geometry featured straight inlet/outlet pipes and a domed compression plate. This optical tracer technique has proven convenient, economical, sensitive to low concentrations of tracer and provides instantaneous pictures of tracer distribution in a ventricle.

Benzenesulfonates↗

Multiple sites of adaptive plasticity in the owl's auditory localization pathway.

In the midbrain auditory localization pathway of the barn owl, a map of auditory space is relayed from the external nucleus of the inferior colliculus (ICX) to the deep and intermediate layers of the optic tectum (OT) and from these layers to the superficial layers. Within the OT, the auditory space map aligns with a visual map of space. Raising young barn owls with a prismatic displacement of the visual field leads to progressive changes in auditory tuning in the OT that tend to realign the auditory space map with the prismatically displaced visual space map. The only known site of this adaptive plasticity is in the ICX, in which the auditory system first creates a map of space. In this study, we identified an additional site of plasticity in the OT. In owls that experienced prisms beginning late in the juvenile period, adaptive shifts in auditory tuning in the superficial layers of the OT exceeded the adaptive shifts that occurred in the deep layers of the OT or in the ICX. Anatomical results from these owls demonstrated that the topography of intrinsic OT connections was systematically altered in the adaptive direction. In juvenile owls, plasticity in the OT increased as plasticity in the ICX decreased. Because plasticity at both sites has been shown to decline substantially in adults, these results suggest that an age-dependent decrease in auditory map plasticity occurs first in the ICX and later at the higher level, in the OT.

Acoustic Stimulation↗

Three-dimensional surface contouring of macroscopic objects by means of phase-difference images.

We report a technique to determine the 3D contour of objects with dimensions of at least 4 orders of magnitude larger than the illumination optical wavelength. Our proposal is based on the numerical reconstruction of the optical wave field of digitally recorded holograms. The required modulo 2pi phase map in any contouring process is obtained by means of the direct subtraction of two phase-contrast images under different illumination angles to create a phase-difference image of a still object. Obtaining the phase-difference images is only possible by using the capability of numerical reconstruction of the complex optical field provided by digital holography. This unique characteristic leads us to a robust, reliable, and fast procedure that requires only two images. A theoretical analysis of the contouring system is shown, with verification by means of numerical and experimental results.

Journal Article↗

[Retinotopic organization in the development of the young trout Salmo gairdneri Rich].

The progression of the retinotopic organization in the optic nerve projections to the contralateral thalamus and tectum was studied in Salmo gairdneri from hatching stage to 3 month old stage. After quadratic lesions of the temporal, dorsal, nasal, or ventral retina, the animals were separated in two groups: one used for Fink and Heimer method or electron microscopic observation and the other one for radioautography after injection in the operated eye of 14C or 3H proline. The analysis of the projections of each retinal quadrant shows that: Projections to thalamus and pretectum are ignorganized and appear progressively during development. On the contrary in tectum and corpus geniculatum, the visual projections are retinotopically organized since hatching. In the whole retino-tectal system, two subsystems develop differently: the naso-ventral retina reaches precociously its permanent target (the posterior tectum), the temporo-dorsal part of the retina links to the anterior tectum and shifts laterally during the first month after hatching, from medial to antero-lateral tectum for temporal projections. The shifting of projections is correlated with development of the medial fascicle of the optic tract. So it appears that the pathways play an important role in the spatio-temporal ordered pattern of terminations of retinal fibers on the tectal surface during development.

Aging↗