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On the spatial mismatch of rod and cone mediated inputs to cat retinal ganglion cells.

The determination of threshold sensitivities of cat retinal ganglion cells to 452 nm-blue and 578 nm-yellow narrow-band lights were undertaken prior to the mapping of the rod- and cone-mediated receptive field centres. In some brisk sustained on-centre retinal ganglion cells two distinct and spatially separated regions were noted such that one region was maximally sensitive to 452 nm-blue and the other to 578 nm-yellow lights. The two wavelength-dependent regions of maximal sensitivity are presumably related to asymmetries between rod- and cone-mediated inputs, rather than between inputs mediated by different classes of cones and correspond, respectively, to the loci of the rod- and cone-mediated centres.

Action Potentials↗

Chemometrical exploration of the wet precipitation chemistry from the Austrian Monitoring Network (1988-1999).

The present paper deals with the application of different chemometric methods to an environmental data set derived from the monitoring of wet precipitation in Austria (1988-1999). These methods are: principal component analysis (PCA); projection pursuit (PP); density-based spatial clustering of application with noise (DBSCAN); ordering points to identify the clustering structures (OPTICS); self-organizing maps (SOM), also called the Kohonen network; and the neural gas (NG) network. The aim of the study is to introduce some new approaches into environmetrics and to compare their usefulness with already existing techniques for the classification and interpretation of environmental data. The density-based approaches give information about the occurrence of natural clusters in the studied data set, which, however, do not occur in the case presented here; information about high-density zones (very similar samples) and extreme samples is also obtained. The partitioning techniques (clustering, but also neural gas and Kohonen networks) offer an opportunity to classify the objects of interest into several defined groups, the patterns of ionic concentration of which can be studied in detail. The visual aids, such as the color map and the Kohonen map, for each site are very helpful in understanding the relationships between samples and between samples and variables. All methods, and in particular projection pursuit, give information about samples with extreme characteristics.

Austria↗

Local networks in visual cortex and their influence on neuronal responses and dynamics.

Networks of neurons in the cerebral cortex generate complex outputs that are not simply predicted by their inputs. These emergent responses underlie the function of the cortex. Understanding how cortical networks carry out such transformations requires a description of the responses of individual neurons and of their networks at multiple levels of analysis. We focus on orientation selectivity in primary visual cortex as a model system to understand cortical network computations. Recent experiments in our laboratory and others provide significant insight into how cortical networks generate and maintain orientation selectivity. We first review evidence for the diversity of orientation tuning characteristics in visual cortex. We then describe experiments that combine optical imaging of orientation maps with intracellular and extracellular recordings from individual neurons at known locations in the orientation map. The data indicate that excitatory and inhibitory synaptic inputs are summed across the cortex in a manner that is consistent with simple rules of integration of local inputs. These rules arise from known anatomical projection patterns in visual cortex. We propose that the generation and plasticity of orientation tuning is strongly influenced by local cortical networks-the diversity of these properties arises in part from the diversity of neighbourhood features that derive from the orientation map.

Animals↗

Functional representation of the finger and face in the human somatosensory cortex: intraoperative intrinsic optical imaging.

We applied the intrinsic optical imaging technique to the human primary somatosensory cortex during brain tumor/epilepsy surgery for nine patients. The cortical surface was illuminated with a Xenon light through an operating microscope, and the reflected light, which passed through a 605 nm bandpass filter, was detected by a CCD camera-based optical imaging system. Individual electrical stimulation of five digits induced changes in the reflected light intensities. Visualizing the intrinsic optical responses, we constructed maps of finger representation in Brodmann's area 1. In the maps, response areas of Digits I to V were sequentially aligned along the central sulcus in the crown of the postcentral gyrus from the latero-inferior region (Digit I) to the medio-superior region (Digit V). The neighboring response areas partially overlapped each other, as previously described in the monkey somatosensory cortex. Similar results were obtained in the face region with stimulation of the three branches of the trigeminal nerve. These results suggest that the overlap of the response areas is a common feature in the somatosensory cortex not only in monkeys, but also in humans.

Adult↗

Equilibrium unfolding of a small bacterial cytochrome, cytochrome c551 from Pseudomonas aeruginosa.

The unfolding of the small cytochrome c551 from the bacterium Pseudomonas aeruginosa has been characterized at equilibrium by circular dichroism (CD) and fluorescence spectroscopy. The process can be described by a two state mechanism and the thermodynamic stability of cytochrome c551 is found to be smaller than that of the larger horse cytochrome c (deltaGw = -8.2 vs. -9.7 kcal/mol); we propose that this finding is related to the absence of an 'omega' loop in the bacterial cytochrome. Cytochrome c551 loses most of its secondary structure at pH 1.5. The acid transition (pKA approximately 2) is highly cooperative (n > or =2); analysis of optical titrations and contact map suggests that (at least) His-16 (proximal Fe3+ ligand) and Glu-70 are both involved in the acid transition. The role of selected hydrophobic, electrostatic and conformational contributions to the overall stability has been investigated by protein engineering. The equilibrium characterization of wild-type and mutant cytochrome c551 supports the view that this small cytochrome is an interesting protein to analyze the thermodynamics and the kinetics of folding in comparison with the widely studied horse cytochrome c.

Acids↗

Corneal topography of excimer laser photorefractive keratectomy using a 6-mm beam diameter. Summit PRK Topography Study Group.

OBJECTIVE: The purpose of the study is to define qualitative patterns of corneal topography after excimer laser photorefractive keratectomy (PRK) using a 6-mm beam diameter, investigate changes in patterns over time, and identify associations of topography patterns with clinical outcomes. DESIGN: Multicenter, prospective cohort study. PARTICIPANTS: Ninety-eight eyes of 90 patients with myopia who had undergone PRK using the Summit Technology, Inc., excimer laser with a 6-mm beam diameter. INTERVENTION: Computer-assisted videokeratography data were analyzed for eyes having undergone PRK. Topography patterns at 3, 6, and 12 months after surgery were classified and associations with clinical outcomes assessed. MAIN OUTCOMES MEASURED: Topography patterns after PRK were determined at 3, 6, and 12 months after surgery. Associations with preoperative characteristics of age and attempted correction, and postoperative outcomes of uncorrected and spectacle-corrected visual acuity, predictability, astigmatism, corneal haze, glare, halo, and patient satisfaction were analyzed. RESULTS: At 1 year, 21.4% of corneas showed a homogeneous topography, 27.6% showed a toric-with-axis configuration, 10.2% showed a toric-against-axis configuration, 7.1% showed an irregularly irregular topography, 24.5% showed a keyhole/semicircular pattern, and 9.2% showed focal topographic variants. From 3 to 6 months, 40.1% of maps changed; from 6 to 12 months, 53.1% of maps changed, generally to optically smoother, regular patterns. Older age and higher attempted correction were associated with the development of more irregular patterns. The irregular groups showed worse predictability than did the regular groups and a tendency for slight overcorrection. The average reported glare/halo of 1.33 (scale = 0 to 5) in this study was less than in a previous study of the 4.5- to 5-mm treatment zone. However, of six patients expressing dissatisfaction with the results of surgery, three ranked their glare or halo at the maximum level. CONCLUSIONS: Topography patterns using a 6-mm beam diameter are identifiable, improve with time, and may affect clinical outcomes after photorefractive keratectomy (PRK). The keyhole/semicircular pattern is more prevalent with a 6 mm treatment zone than with smaller treatment zones. Although optical side effects of glare and halo appear to be reduced with the 6-mm treatment, a small number of patients still report substantial glare or halo after the procedure.

Astigmatism↗

Study of transfer ribonucleic acid unfolding by dynamic nuclear magnetic resonance.

Nuclear magnetic resonance (NMR) measurements of proton exchange were performed on yeast tRNAPhe, and in much less detail on Escherichia coli tRNAfMet, over a range of Mg2+ concentrations and temperatures, at neutral pH and 0.1 M NaCl. The resonances studied were those of ring nitrogen protons, resonating between 10 and 15 ppm downfield from sodium 3-(trimethylsilyl)-1-propanesulfonate, which partake in hydrogen bonding between bases of secondary and tertiary pairs. Methods include saturation--recovery, line width, and real-time observation after a change to deuterated solvent. The relevant theory is briefly reviewed. We believe that most of the higher temperature rates reflect major unfolding of the molecule. For E. coli tRNAfMet, the temperature dependence of the rate for the U8--A14 resonance maps well onto previous optical T-jump studies for a transition assigned to tertiary melting. For yeast tRNAPhe, exchange rates of several resolved protons could be studied from 30 to 45 degrees C in zero Mg2+ concentration and had activation energies on the order of 40 kcal/mol. Initially, the tertiary structure melts, followed shortly by the acceptor stem. At high Mg2+ concentration, relatively few exchange rates are measurable below the general cooperative melt at about 60 degrees C; these are attributed to tertiary changes. Real-time observations suggest a change in the exchange mechanism at room temperature with a lower activation energy. The results are compared with those obtained by other methods directed toward assaying ribonucleic acid dynamics.

Escherichia coli↗

Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation.

Modern functional neuroimaging methods, such as positron-emission tomography (PET), optical imaging of intrinsic signals, and functional MRI (fMRI) utilize activity-dependent hemodynamic changes to obtain indirect maps of the evoked electrical activity in the brain. Whereas PET and flow-sensitive MRI map cerebral blood flow (CBF) changes, optical imaging and blood oxygenation level-dependent MRI map areas with changes in the concentration of deoxygenated hemoglobin (HbR). However, the relationship between CBF and HbR during functional activation has never been tested experimentally. Therefore, we investigated this relationship by using imaging spectroscopy and laser-Doppler flowmetry techniques, simultaneously, in the visual cortex of anesthetized cats during sensory stimulation. We found that the earliest microcirculatory change was indeed an increase in HbR, whereas the CBF increase lagged by more than a second after the increase in HbR. The increased HbR was accompanied by a simultaneous increase in total hemoglobin concentration (Hbt), presumably reflecting an early blood volume increase. We found that the CBF changes lagged after Hbt changes by 1 to 2 sec throughout the response. These results support the notion of active neurovascular regulation of blood volume in the capillary bed and the existence of a delayed, passive process of capillary filling.

Animals↗

Attentional modulation of receptive field structure in area 7a of the behaving monkey.

Spatial attention modulates the activity of inferior parietal neurons. A statistically rigorous approach to classical retinotopic mapping was used to quantify the receptive fields of area 7a neurons under 2 attentional conditions. Measurements were made with retinal stimulation held constant and the locus of attention manipulated covertly. Both tasks required central fixation but differed in the locus of covert attention (either on the center fixation point or on a peripheral square target in one of 25 locations). The neuron's identity over the recording session was confirmed using chaos theory to characterize unique temporal patterns. Sixty-six percent of the neurons changed prestimulus activity based on task state. Retinotopic mapping showed no evidence for foveal sparing. Attentional factors influenced visual responses for approximately 30% of the neurons. Two types of modulation were equally observed. One group of cells had a multiplicative scaling of response, with equal instances of enhancement and suppression. A second group of cells had a complex interaction of visual and attentional signals, such that spatial tuning was subject to a nonlinear modulation across the visual field based on attentional constraints. These 2 cell groups may have different roles in the shift of attention preceding motor behaviors and may underlie shifts in parietal retinotopic maps observed with intrinsic optical imaging.

Algorithms↗

Intraoperative optical imaging of human face cortical topography: a case study.

We used intrinsic signal optical imaging to obtain maps of human somatosensory cortex during electrocutaneous stimulation of the face during a neurosurgical procedure for epilepsy. We found that human face somatotopy is organized like the macaque or cebus monkey, with peri-orbital skin located medial to peri-buccal skin, and that cortical magnification in the human is comparable to that in non-human primates. This study demonstrates that intrinsic signal imaging can be performed on humans during operative procedures with sufficient spatial resolution to reveal high-resolution topographic maps.

Adult↗

Differential responses of single reticulospinal cells to spatially localized stimulation of the optic tectum in a teleost fish, Salmo trutta.

To determine whether the topographically organized retinal input to the optic tectum is subsequently mapped onto the reticular formation, the responses of antidromically identified reticulospinal cells to tectal surface stimulation were investigated in 45 decerebrated, paralysed trout. The tectum was stimulated through a silver ball surface electrode at 24 different locations, and extracellular recordings were made from the rhombencephalic brainstem with glass microelectrodes filled with a 10% solution of horseradish peroxidase (HRP) in Tris buffer (pH 7.4). After recording, the HRP was, in some cases, iontophoretically expelled from the pipette to identify its location and visualized in histological sections by a modified Hanker-Yates method. Individual reticulospinal neurons discharged 1-4 spikes at short latency in response to stimulation of each of the 24 tectal locations. From one tectal location per cell, this initial response was followed by a late, sustained burst. With a short stimulus train (6 pulses, 55 Hz) the burst could last for over a second with discharge rates of up to 500 Hz. Sometimes this burst could be evoked from neighbouring tectal locations, but only by greatly increasing the stimulus strength. We conclude that the reticular formation receives a highly divergent monosynaptic connection from all locations of the tectum and that the longer latency, sustained burst response is due to a mapped connection between the tectum and the reticular formation. Since the late burst could be preceded by a silent period lasting for approximately 32 ms, we cannot rule out a dependence on interneurons situated between the tectum and the reticulospinal cells.

Animals↗

Spontaneous atrial fibrillation initiated by triggered activity near the pulmonary veins in aged rats subjected to glycolytic inhibition.

Aging and glycolytic inhibition (GI) are known to alter intracellular calcium ion (Ca(i)(2+)) handling in cardiac myocytes, causing early afterpotentials (EADs) and delayed afterpotentials. We hypothesized that aging and GI interact synergistically in intact hearts to generate EADs and triggered activity leading to atrial fibrillation (AF). We studied isolated and Langendorff-perfused hearts of young (age 3-5 mo, N = 8) and old (age 27-29 mo, N = 14) rats subjected to GI (0 glucose + 10 mmol/l pyruvate). Epicardial atrial activation maps were constructed using optical action potentials, while simultaneously monitoring Ca(i)(2+) by means of dual-voltage and calcium-sensitive fluorescent dyes. During GI, spontaneous AF occurred in 13 of 14 old but in no young rats. AF was initiated by EAD-induced triggered activity at the left atrial pulmonary vein junction (LA-PVJ). The triggered activity initially propagated as single wave front, but within 1 s degenerated into multiple wavelets. The EADs and triggered activity in the old atria were associated with significantly elevated diastolic Ca(i)(2+) levels at the LA-PVJ, where the time constant tau of the Ca(i)(2+) transient decline and action potential duration were significantly (P < 0.01) prolonged compared with atrial sites 5 mm away from LA-PVJ. During GI and rapid atrial pacing, spatially discordant APD and Ca(i)(2+) transient alternans developed in the old but not young atria, leading to AF. Atria in old rats had significantly more fibrotic tissue than atria in young rats. We conclude that GI interacts with the aged and fibrotic atria to amplify Ca(i)(2+) handling abnormalities that facilitate EAD-mediated triggered activity and AF.

Action Potentials↗

Subthreshold stimulation of Purkinje fibers interrupts ventricular tachycardia in intact hearts. Experimental study with voltage-sensitive dyes and imaging techniques.

The effects of subthreshold stimulation (STS) delivered during right atrial pacing and ventricular tachycardia (VT) were investigated in Langendorff-perfused guinea pig hearts. The hearts were stained with a voltage-sensitive dye (RH 421) to map the propagation of optical action potentials. Sustained VT was reliably induced by 5-second trains (cycle length [CL], 25 to 50 milliseconds; duration, 0.5 to 10 milliseconds; and voltage, 2x threshold voltage) of impulses (n = 12 hearts) or a single premature beat (n = 6). The location of extrastimuli was not critical to the induction of VT, but the diameter of the heart had to be > or = 14.5 mm. During VT, heart rate increased from 200 to 600 beats per minute; action potential durations decreased from 112 to 175 milliseconds to 60 to 105 milliseconds, with no diastolic interval. Activation on the epicardium spread anisotropically, but VT decreased the "apparent" maximum conduction velocity (theta max) by 68% and altered the orientation of the major axis from beat to beat. Activation patterns and theta max measured during VT were similar to patterns recorded during direct pacing of the ventricle and indicated that Purkinje fibers no longer propelled ventricular excitation. STS (CL, 25 to 50 milliseconds; duration, 0.5 to 25 milliseconds; and voltage, 0.5x to 0.8x threshold; trains of 2.0 to 2.5 seconds) interrupted VT when applied to Purkinje fibers lining the endocardium (n = 6) but failed to interrupt VT when applied to the epicardium (n = 8). In atrial pacing, STS delivered to the endocardium increased theta max from 2.44 +/- 0.32 (mean +/- SEM) to 3.63 +/- 0.21 m/s in a local region surrounding the first activation sites (n = 4). Alternatively, VT could be terminated by reducing theta max (approximately 55%) with procainamide (10 mumol/L) (n = 6). STS terminates VT by synchronizing ventricular excitation most likely by increasing local conduction and/or improving the coupling between Purkinje and ventricular cells.

Action Potentials↗

Analysing one isolated single walled carbon nanotube in the near-field domain with selective nanovolume Raman spectroscopy.

In this paper, we describe a new method to the selective nanovolume analysing of one isolated single walled carbon nanotube (SWNT). This concept is based on actually available imaging micro-spectrometry systems for working in near-field domain combined with a stigmatic solid immersion lens. This combination of different analytical methods, and modified and configured equipment entitles us to expand the functionality toward a three-dimensional (3D) nanovolume Raman mapping and photoluminescence intensity with a possible discrimination in polarization, as well as photoluminescence decaytime constant mapping with their unique combination. Subsequently, selective spectra can be acquired from the same location on the samples. By spectrally selecting a SWNT, we registered the spatial distribution of the emitted photons in x, y, z vectors to determine the position of a SWNT in the near-field domain. For the SWNTs that are localized with an accuracy better than 18 nm in the x, y and <1 nm in the z directions, we demonstrate an analytical sensitivity close to a single nanotube with unity throughput. This near-field capability is applied to resolve local variations unambiguously in the Raman spectrum along one single SWNT. Finally, in this paper, we report what we believe to be the first evidence of Raman mapping and 3D real optical imaging of carbon nanotubes with near-field resolution.

Image Processing, Computer-Assisted↗

Kinetics of retinal lipoprotein precipitation and elimination after closure of subretinal new vessels.

PURPOSE: To study the kinetics of retinal precipitation and elimination of lipoprotein in relation to photodynamic therapy of subretinal new vessels. METHODS: This was a retrospective observational study of subretinal precipitate before and after photodynamic therapy for subfoveal new vessels secondary to age-related macular degeneration in 14 eyes demonstrating precipitate at one or more visits, using digital red-free gray-scale fundus photography, intravenous fluorescein angiography, optical coherence tomography, and morphometric mapping. RESULTS: In 14 eyes of 14 patients, the area covered by lipoprotein precipitate increased from a mean of 0.54 optic disc areas (range, 0-2.61) before treatment to a mean of 0.65 optic disc areas (range, 0.01-3.04) at 45 d after treatment (P = 0.18). Eyes with a serous detachment at baseline, before the initial treatment (n = 10) demonstrated more treatment-related precipitation than eyes without a serous detachment at baseline (n = 4; P = 0.034). Two eyes with a large amount of precipitate and a long follow-up demonstrated net elimination of precipitate from approximately 100 days after the initial treatment, with uniexponential precipitate half-lives of 43 and 32 days. CONCLUSIONS: Photodynamic therapy for subfoveal new vessels may be associated with retinal precipitation of lipoprotein, presumably because early extraction of water and salts from the subretinal fluid increases the concentration of leaked plasma proteins. Despite reperfusion of the subretinal vessels, macromolecular leakage appears to cease within 100 days, indicating that functional maturation of the new vessels has occurred, with an associated decrease in pore size.

Aged↗