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Wide-field nondirectional visual units in the pretectum: do they suppress ocular following of saccade-induced visual stimulation.

1. Direction-selective neurons in the nucleus of the optic tract (NOT) provide motion signals for controlling ocular following responses. When stimulated at low temporal and high spatial frequencies of motion (slow speeds), these retinal-slip neurons produce directional responses. When stimulated by motion at high temporal and low spatial frequencies (the visual conditions during saccades) the spontaneous activities of the neurons are inhibited by motion in all directions. A second class of neurons in, or near, the NOT have large receptive fields, are nondirectional, and are tuned to detect the same spatial and temporal stimuli that induce nondirectional inhibition in the retinal-slip neurons. We suggest that the nondirectional cells provide an inhibitory input for the retinal-slip neurons and therefore prevent ocular following of the visual displacements that accompany saccades.

Animals↗

The L1 cell adhesion molecule is essential for topographic mapping of retinal axons.

The retinocollicular projection is a preferred axon guidance pathway for investigating molecular mechanisms of synaptic targeting in the mammalian CNS. Here we identify a previously unrecognized role of the L1 cell adhesion molecule in topographic mapping of retinal ganglion cell (RGC) axons to their targets in the mouse superior colliculus (SC). L1 was transiently expressed on RGC axons during axon growth and targeting. DiI labeling of retinal axons revealed that temporal axons of L1-minus mice bypassed correct target locations in the anterior SC, forming termination zones at incorrect posterior sites, which were often skewed along the mediolateral axis. During development of the retinotopic map L1-minus temporal axons extended across the anteroposterior axis of the SC like wild-type axons but failed to arborize at normal anterior target sites. L1-minus RGC axons exhibited normal crossing at the optic chiasm and fasciculation of the optic nerve. Results suggest that retinal axons require the function of L1 in addition to repellent EphA guidance receptors to achieve proper topographic mapping.

Animals↗

The functional organization of the isthmo-optic nucleus in the pigeon.

1. Extracellular single unit records were taken from the isthmo-optic nucleus of the pigeon, locating the nucleus by the antidromic field potential resulting from electrical stimulation of the isthmo-optic tract.2. Visual receptive fields were investigated for 248 units, and were classed into three types: directionally selective, directionally non-selective, and posterior minimum. They ranged from 3 to 10 degrees in extent.3. The topographical representation of the visual field in the nucleus was investigated by histological verification of electrode tracks, and a correlation with the receptive field sequences. Vertical descent through the nucleus resulted in an upwards progression of receptive field locations. Lateromedial passage through the nucleus resulted in a forwards progression of receptive field locations.4. The representation of the lower visual field is greater than that of the superior visual field: that for the central parts of the inferior field is greater than that for the periphery, and the representation of the anterior inferior quadrant is greater than that of the posterior inferior quadrant.

Animals↗

The role of the posterior parietal lobe in prism adaptation: Failure to adapt to optical prisms in a patient with bilateral damage to posterior parietal cortex.

We studied a patient (J.J.) with bilateral damage to those regions of the posterior parietal cortex (PPC) thought to be involved in prism adaptation. We demonstrated, for the first time in a parietal patient, that J.J. was unable to adapt to the visual perturbation induced by the optical prisms with either hand within four times the number of trials required by healthy adult subjects. We offer a novel account for the role of the PPC in prism adaptation: that the reach direction to the veridical target location specified in extrinsic limb-based coordinates must be de-coupled from the gaze direction to the perceived target location specified by intrinsic oculocentric coordinates in order to produce spatially accurate movements. This spatial discrepancy between gaze direction and reach direction may provide the necessary training signal required by the cerebellum to update the current internal model used to maintain spatial congruency between visual and proprioceptive maps of peripersonal space. The hypothesis is discussed in relation to recent disconnectionist accounts of optic ataxia.

Adaptation, Physiological↗

Axodendritic contacts onto calcium/calmodulin-dependent protein kinase type II-expressing neurons in the barn owl auditory space map.

In the owl midbrain, a map of auditory space is synthesized in the inferior colliculus (IC) and conveyed to the optic tectum (OT). Ascending auditory information courses through these structures via topographic axonal projections. Little is known about the molecular composition of projection neurons or their postsynaptic targets. To visualize axodendritic contacts between identified cell types, we used double-label immunohistochemistry, in vivo retrograde tracing, in vitro anterograde tracing, high-resolution confocal microscopy, three-dimensional reconstruction and fly-through visualization. We discovered a major class of IC neurons that strongly expressed calcium/calmodulin-dependent protein kinase type II, alpha subunit (CaMKII). The distribution of these cells within the IC was mostly restricted to the external nucleus of the IC (ICX), in which the auditory space map is assembled. A large proportion of ICX-OT projection neurons were CaMKII positive. In addition to being the principal outputs, CaMKII cells were in direct contact with axonal boutons emanating from the main source of input to ICX, the lateral shell of the central nucleus of the inferior colliculus (ICCls). Numerous sites of putative synaptic contact were found on the somata, proximal dendrites, and distal dendrites. Double-label immunoelectron microscopy confirmed the existence of synapses between ICCls axons and the dendrites of CaMKII cells. Collectively, our data indicate that CaMKII ICX neurons are a cellular locus for the computation of auditory space-specific responses. Because the ICCls-ICX projection is physically altered during experience-dependent plasticity, these results lay the groundwork for probing microanatomical rearrangements that may underlie plasticity and learning.

Animals↗

Topography of orientation centre connections in the primary visual cortex of the cat.

The functional topography of lateral connections to orientation-centre zones was studied by optical imaging of intrinsic signals in combination with tracer injections (fluorescent beads and biocytin) and electrophysiological recordings. Three-dimensional reconstruction of anterogradely labelled axon terminals and retrogradely labelled somata revealed a uniform distribution across all orientations in a non-patchy manner. The overall lateral extent of the labelling was 3-4 mm in layer 3, that is about half of the extent observed for orientation domain connections in the same layer. These bulk injection data are in contrast with the reportedly sharp orientation tuning of neurons of centre zones and suggest that orientation specificity here does not require highly specific connections. Nonetheless, another plausible scenario is that orientation centre connections are orientation specific but their specificity present at the single cell level cannot be revealed by bulk labelling due to their large spatial overlap.

Animals↗

Electrophysiological evidence for transient topographic organization of retinotectal projections during optic nerve regeneration in the lizard, Ctenophorus ornatus.

In the lizard, Ctenophorus ornatus, anatomical studies have revealed that optic axons regenerate to visual centers within 2 months of nerve crush but that, from the outset, the regenerated projections lack topographic order (Beazley et al., 1997; Dunlop et al., 1997b). Here we assess the functional topography of the regenerated retinotectal projections by electrophysiological recording of extracellular multiunit responses to visual stimulation and by observing the lizards' ability to capture live prey. At the completion of the electrophysiology, DiI was applied locally to the retina and the topography of the tectal projection later assessed. Electrophysiology revealed that, at 2-4.2 months, responses were weak and habituated readily; no retinotopic order was detected. Between 4.5-6 months, responses were more reliable and the majority of lizards displayed a crude retinotopic order, especially in the ventro-temporal to dorso-nasal retinal axis. Although responses were variable between 6-9 months, they tended to be more reliable again thereafter. However, from 6-18 months, the projection consistently lacked topography with many retinal regions projecting to each tectal locus. Lizards, including those with electrophysiological evidence of crude retinotopy, were consistently unable to capture live prey using the experimental eye. Labelling with DiI confirmed the absence of anatomical retinotopy throughout. Taken together, the electrophysiological and anatomical data indicate that retinotopically appropriate axon terminals (or parts thereof) are transiently active whilst inappropriately located ones are silent. Presumably in lizard map-making cues fade with time and/or the mechanisms are lacking to stabilize and refine the ephemeral map. Moreover, the transient retinotopy is insufficient for useful visual function.

Animals↗

Spreading of hemiretinal projections in the ipsilateral tectum following unilateral enucleation: a study of optic nerve regeneration in Xenopus with one compound eye.

Right compound eyes were formed in Xenopus embryos at stages 32-33 by the fusion of two nasal (NN), two ventral (VV) or two temporal (TT) halves. Shortly after metamorphosis the optic nerve from the compound eye was sectioned and the left intact eye removed. The retinotectal projections from the compound eye to the contralateral and ipsilateral tecta were studied by [3H]proline autoradiography and electrophysiological mapping between 6 weeks and 5 months after the postmetamorphic surgery. The results showed that NN and VV eyes projected to the entire extent of both tecta. In contrast, optic fibre projection from TT eyes, although more extensive than the normal temporal hemiretinal projection, failed to cover the caudomedial portion of the tecta. The visuotectal projections in all three combinations corresponded to typical reduplicated maps to be expected from such compound eyes, where each of the hemiretinae projected across the contralateral and ipsilateral tecta in an overlapping fashion. The rapid expansion of the hemiretinal projections of the compound eyes in the ipsilateral tectum following the removal of the resident optic fibre projection suggests that tectal markers may be carried and deployed by the incoming optic fibres themselves.

Action Potentials↗

Superoxide dismustase mimetic tempol decreases blood pressure by increasing renal medullary blood flow in hyperinsulinemic-hypertensive rats.

Insulin resistance and compensatory hyperinsulinemia often coexist in hypertensive patients, which may play a role in the development of hypertension. Because medullary blood flow (MBF), which is strongly influenced by the nitric oxide (NO) system, is thought to be an important component of blood pressure and sodium balance, we focused particularly on MBF in fructose-induced hypertensive rats. Moreover, it has been reported that the increased reactive oxygen species (ROS) in the kidney may contribute to the development of hypertension. Our study was thus designed to test the hypotheses that MBF is diminished in fructose-hypertensive rats (FFR) and that administration of tempol, a membrane-permeable mimetic of superoxide dismutase (SOD), decreases mean arterial pressure (MAP) by increasing MBF. Male Sprague-Dawley rats (180 to 200 g) were divided into 6 groups: control untreated (C, n = 5), control tempol-treated (in drinking water) (CT, n = 4), control L-arginine-treated (in drinking water) (CA, n = 6), fructose-fed untreated (F, n = 7), fructose-fed tempol-treated (FT, n = 7), and fructose-fed L-arginine-treated rats (in drinking water) (FA, n = 6). MAP and 24-hour urine samples were measured weekly over a 4-week test period. Changes in MBF, cortical blood flow (CBF), and renal blood flow (RBF) were determined by implanted optical fiber-, laser- and pulse-Doppler flow measurement techniques 4 weeks after starting the diet. Fructose feeding resulted in hyperinsulinemia, significantly elevated MAP, decreased MBF without changes in RBF or CBF, and decreased sodium excretion in the F group compared to the C group. Administration of tempol significantly decreased MAP and plasma insulin in contrast to increased MBF and sodium excretion in the FT group compared to those in the F group. Results indicated that MBF played an important role in the development of hypertension in the F group. Impairment of renal medullary NO systems may induce sustained elevation of blood pressure and retention of sodium in fructose-fed rats. The decrease in MAP with an increase of MBF in the FT group is consistent with the hypothesis that tempol increases the level of NO available to influence mechanisms involved in the control of MBF.

Animals↗

Optical verification of a technique for in situ ultrasonic measurement of articular cartilage thickness.

Several investigators have used pulse-echo ultrasonics to measure the thickness of articular cartilage in situ. The underlying assumption in all measurements was that the second reflection used in thickness calculations was from the calcified-cartilage/cartilage boundary (tidemark). To investigate this assumption, the thickness of 24 cartilage plugs excised from a human femoral head was measured both ultrasonically and optically. Measurements established that the second reflection was from the tidemark and validated the ultrasonic technique as a method of mapping the thickness distribution of articular cartilage in synovial joints in situ.

Acetabulum↗

Organic alternatives to quantum dots for intraoperative near-infrared fluorescent sentinel lymph node mapping.

Intraoperative near-infrared (NIR) fluorescence imaging provides the surgeon with real-time image guidance during cancer and other surgeries. We have previously reported the use of NIR fluorescent quantum dots (QDs) for sentinel lymph node (SLN) mapping. However, because of concerns over potential toxicity, organic alternatives to QDs will be required for initial clinical studies. We describe a family of 800 nm organic heptamethine indocyanine-based contrast agents for SLN mapping spanning a spectrum from 775 Da small molecules to 7 MDa nanocolloids. We provide a detailed characterization of the optical and physical properties of these contrast agents and discuss the advantages and disadvantages of each. We present robust methods for the covalent conjugation, purification, and characterization of proteins with tetra-sulfonated heptamethine indocyanines, including mass spectroscopic site mapping of highly substituted molecules. One contrast agent, NIR fluorescent human serum albumin (HSA800), emerged as the molecule with the best overall performance with respect to entry to lymphatics, flow to the SLN, retention in the SLN, fluorescence yield and reproducibility. This preclinical study, performed on large animals approaching the size of humans, should serve as a foundation for future clinical studies.

Chromatography, Gel↗

Evaluation of optical source-detector configurations for tomographic reconstruction of chemical concentrations in indoor air.

This article reports on numerical studies to evaluate and compare optical remote sensing configurations for tomographically reconstructing pollutant concentrations in indoor air. With a remote sensing/computed tomography system, two-dimensional maps of pollutant concentrations with good spatial resolution can be created for an entire room. The successful use of such a system for exposure assessment, ventilation assessment, or source monitoring depends on the remote sensing configuration. A systematic method was developed to evaluate the performance of 10 configurations. One hundred and twenty test maps were reconstructed with an algebraic reconstruction method using all 10 configurations; reconstruction quality was evaluated using 4 criteria. Reconstruction quality was related to the number and location of detectors in the room and the complexity of the test maps. Configurations using the same number of detectors placed in different locations resulted in reconstructions that differed in quality. The effect of reducing the number density of rays on reconstruction quality was studied. Based on these simulations, two configurations that used four detectors to scan the room were selected, and their performance was evaluated in the presence of various levels of measurement noise. Two configurations that used four detectors were most suited for exposure assessment. It was found that when designing a configuration, the number and independence of rays should be maximized. Results underscored the need to thoroughly test configurations through numerical studies prior to field implementation; a wide variety of concentration maps, relevant to the application, should be tested under both ideal and nonideal sampling conditions.

Air Pollutants↗

Population magnitudes and distribution of the major modal classes of cat retinal ganglion cell as estimated from HRP filling and a systematic survey of the soma diameter spectra for classical neurones.

A survey of diameter spectra in presented for classic neurones of the cat retinal ganglion cell layer. From these, with the aid of retrograde HRP filling for central retina, a set of density distribution maps has been prepared for each of the major modes of the neuronal diameter spectrum. The total population of classical neurones, the presumed ganglion cells of Hughes ('75), confirms published values with a minimum of some 207,000 comprised 5,600 cells in the alpha mode, 80,700 cells in the beta mode, and 120,700 cells in the gamma mode. A proportion of classical neurones in the gamma mode do not fill by retrograde transport of HRP from either optic nerve or superior colliculus. Their morphology is characteristic and includes a conspicuous basophilic nuclear bar or fold; they remain subsequent to ganglion cell retrograde degeneration and resemble some profiles of the amacrine layer. It is presumed that they represent a class of displaced amacrine cells. Estimates based on ganglion cell identification by HRP filling indicate populations of about 80,000 cells in both the gamma and the beta modes and a total count of about 170,000 ganglion cells; a good agreement with Hughes and Wässle's ('76) optic nerve fibre count, but lower than the classic neurone count. It is concluded that the distribution maps for ganglion cells in each of the three modes of the soma diameter spectra are similar in form and resemble that of the total neurone density map. The ganglion cell population of the gamma mode in the visual streak is not found to increase in proportion relative to that of the beta mode, as has been reported elsewhere.

Animals↗

Visual discrimination impairments after lesions in zona incerta or lateral terminal nucleus of accessory optic tract.

Possible visual functions of zona incerta (ZI) and lateral terminal nucleus of the accessory optic tract (LTN) in rats were investigated by comparing the effects of localized lesions on a series of discrimination learning tasks. In Experiment 1 animals with ZI lesions were impaired on a simultaneous black versus white (BW) discrimination but not on a simultaneous horizontal versus vertical (HV) task. Animals with LTN lesions were impaired on HV but not on BW. Rats with ZI lesions were impaired on a successive bright versus dim but not a successive HV discrimination when subsequently tested in Experiment 2. Animals with LTN lesions were impaired on both tasks. The results are related to the possibility that visual intensity information gains access to the motor system through a pathway running from the ventral lateral geniculate nucleus to the basal ganglia via ZI. Since LTN lesions impaired acquisition of a HV discrimination, a task highly susceptible to the effects of geniculostriate ablation, it is suggested that such lesions impair the use of visual information without distroying the sensory channels mediating the discrimination.

Animals↗

New insights into the hemodynamic blood oxygenation level-dependent response through combination of functional magnetic resonance imaging and optical recording in gerbil barrel cortex.

Fast, low-angle shoot functional magnetic resonance imaging (fMRI), based on the blood oxygenation level-dependent (BOLD) effect, was combined with optical recording of intrinsic signals (ORIS) and 2-deoxyglucose labeling in gerbil barrel cortex. We observed over the activated barrel a positive BOLD signal and increased levels of deoxyhemoglobin and total hemoglobin during each period of prolonged (30 sec) D2 vibrissal stimulation. These data show that the hemodynamic basis of this fMRI signal is not necessarily a washout of deoxyhemoglobin, as generally assumed. Instead, they suggest that a positive BOLD signal can also be caused by a local increase of blood volume, even if deoxyhemoglobin levels are persistently elevated. We also show that this alternative interpretation is consistent with theoretical models of the BOLD signal. The changes in BOLD signal and blood volume, which are most tightly correlated with the periodic stimulation, peak at the site of neuronal activation. These results contribute to the understanding of the hemodynamic mechanisms underlying the BOLD signal and also suggest analysis methods, which improve the spatial localization of neuronal activation with both fMRI and ORIS.

Animals↗

BDNF modulates, but does not mediate, activity-dependent branching and remodeling of optic axon arbors in vivo.

The proper development of axon terminal arbors and their recognition of target neurons depend, in part, on neuronal activity. Neurotrophins are attractive candidate signals to participate in activity-dependent development and refinement of neuronal connectivity. In the visual system, brain-derived neurotrophic factor (BDNF) has been shown to modulate the elaboration and refinement of axonal arbors and to participate in the establishment of topographically ordered visual maps. By examining in vivo with time-lapse microscopy the effects of activity blockade and BDNF on optic axon arborization, I show that the dynamic mechanisms by which neurotrophins and neuronal activity regulate axon arborization differ. Acute retinal activity blockade by intraocular injection of tetrodotoxin (TTX) rapidly and significantly increased branch addition and elimination, thus interfering with axon branch stabilization. The effects of activity blockade on branch dynamics resulted in increased arbor complexity in the long term and were prevented by altering endogenous BDNF levels at the target. BDNF promoted axon arborization by increasing branch addition and lengthening, without affecting branch elimination. Activity blockade, however, did not prevent the growth-promoting effects of BDNF, indicating that BDNF can affect axon arborization even in the absence of activity. Together this evidence indicates that BDNF acts as a modulator, but not as a direct mediator, of activity during the morphological development of neurons. Consequently, neuronal activity and BDNF use distinct but interactive mechanisms to control the development of neuronal connectivity; BDNF modulates axon arborization by promoting growth, neuronal activity participates in axon branch stabilization, and together these two signals converge to shape axon form.

Action Potentials↗

Spectral Fraunhofer regime: time-to-frequency conversion by the action of a single time lens on an optical pulse.

We analyze a new regime in the interaction between an optical pulse and a time lens (spectral Fraunhofer regime), where the input pulse amplitude is mapped from the time domain into the frequency domain (time-to-frequency conversion). Here we derive in detail the conditions for achieving time-to-frequency conversion with a single time lens (i.e., for entering the spectral Fraunhofer regime) as well as the expressions governing this operation. Our theoretical findings are demonstrated both numerically and experimentally. A comparative study between the proposed single-time-lens configuration and the conventional dispersion + time-lens configuration for time-to-frequency conversion is also conducted. Time-to-frequency conversion with a single time lens can be used for applications similar to those previously proposed for the conventional time-to-frequency converters, e.g., high-resolution measurement of fast optical temporal waveforms. Moreover, our results also indicate that the spectral Fraunhofer regime provides additional capabilities for controlling and processing optical pulses.

Journal Article↗