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Spatial distribution of blastomeres is dependent on cell division order and interactions in mouse morulae.

Spatial distribution of blastomeres was examined in 16- to 30-cell morulae obtained from aggregates of 1/2----1/2 and 1/2----2/4 blastomeres. The advanced blastomeres (2/4) contributed disproportionately more inner cells while there was a corresponding decline in the contribution from the delayed blastomere (1/2) so that a balance between the total number of inner and outer cells was retained. There was, however, no marked change in the relative number of outer cells. It is suggested that once formed, the inner more adhesive cells divide relatively faster than the outer cells whose behaviour is dictated by the inner cells. The outer less adhesive cells spread over the inner cells; cell spreading is incompatible with division. The degree to which cell spreading and retardation of division of outer cells occurs may be dictated by the number of inner cells present at any one time and this partly determines the entry of further cells inside. The suggested mechanism for cell allocation is highly flexible and, indeed, essential to encompass the wide variety of patterns of cell interactions and distribution observed in morulae. It is also proposed that the retardation of division of outer cells may trigger differentiation of trophectoderm by inducing endoreduplication and the blastomeres delayed from dividing for the longest period of time may mark down the abembryonic pole and establish the embryonic-abembryonic axis.

Animals↗

The push-pull action of dopamine on spatial tuning of the monkey retina: the effects of dopaminergic deficiency and selective D1 and D2 receptor ligands on the pattern electroretinogram.

Retinal dopamine depletion in monkeys using either systemic MPTP or 6-OHDA results in attenuated electroretinographic (ERG) responses to peak spatial frequency stimuli. Diverse dopamine receptors have been identified in the primate retina. ERG studies performed using Haloperidol (a mixed antagonist), L-Sulpiride (D2 antagonist) and CY 208-243 (a D1 agonist) cause spatial frequency dependent diverse effects. 'Tuning' of the normal spatial contrast response PERG, was quantified by dividing the amplitude of the response at the peak spatial frequency with the amplitude to the low spatial frequency response yielding a number greater than one. Tuning for the pharmacological experiments was defined by dividing the actual amplitude obtained at the normal peak response with the actual amplitude at the low spatial frequency response. The PERG spatial contrast response function is discussed as the envelope output of retinal ganglion cells or the average or 'equivalent' retinal ganglion cell. However, we postulate the existence of two dopamine sensitive pathways with different weights for two classes of ganglion cells. It is inferred that D1 receptors are primarily affecting the 'surround' organization of ganglion cells with large centers, while D2 post-synaptic receptors contribute to 'center' response amplification of ganglion cells with smaller centers. These inferences are consistent with some lower vertebrate data. It is also inferred that low affinity D2 autoreceptors may be involved in the D1 'surround' pathway. An understanding of the logic performed by retinal D1 and D2 receptors may be useful to discern the functional role of diverse dopamine receptors in DA circuits elsewhere in the CNS.

Animals↗

Characterization of measurement system effects in ultrasonic scattering experiments.

A general model is developed to characterize the effect of an ultrasonic measurement system on the experimental determination of ultrasonic scattering as a function of angle and frequency. The model includes arbitrary emitter beams and detector apertures as angular spectra of plane waves. Arbitrary emitted pulses and detector time gates are incorporated through frequency spectra of temporal harmonics. A transformation of variables is employed to express the spectrum of the measured pressure as a product in wave space of a system function and the Fourier transform of the medium variations. The mean-square value of the measured pressure spectrum is similarly expressed as a product of the squared magnitude of the system function and the power spectrum of the medium variations. The measured quantities are shown to become scaled values of intrinsic scattering characteristics when the system function weight is concentrated relative to the medium characteristics in wave space. The assumption of an indefinitely long detector gate is used to represent the system function as a product in which one factor is a beam function dependent on spatial frequency and the other factors are dependent on temporal frequency. Beam-function calculations as well as calculations of second moments and overall beam weight are made for identical Gaussian-shaped emitter and detector apertures to illustrate the blurring and weighting effects of measurement system beam patterns as a function of scattering angle. The moment calculations are shown to identify circumstances when the medium variation function can be factored out from under the integral and the measurement represented as a simple product of the medium properties and a measurement system weight. The results may be used to design scattering experiments in which degradations due to system effects are within acceptable limits.

Computer Simulation↗

Functional activation using apparent diffusion coefficient-dependent contrast allows better spatial localization to the neuronal activity: evidence using diffusion tensor imaging and fiber tracking.

Recent studies suggested that functional activation using apparent diffusion coefficient (ADC) contrast can be used to detect synchronized functional MRI (fMRI) signal changes during brain activation. Such changes may reflect better spatial localization to the smaller vessels, which are closely coupled to the true neuronal activation. Since it is generally believed that there are neural pathways among neuronally relevant areas, methods that would allow clear delineation of such pathways could help validate the neuronal relevance of the activated functional areas. The development of diffusion tensor imaging (DTI) has shown promise in detailed nerve fiber tracking. In this report, DTI was adopted to track the fiber connections among the discrete areas determined using the ADC contrast, in an effort to confirm the neuronal origin of these activated areas. As a comparison, activated areas using blood oxygenation level-dependent (BOLD) contrast were also obtained. Our results showed that the areas determined by the ADC contrast consistently allowed better fiber tracking within, while the BOLD-activated areas were more spatially diffused due to the smearing effect of brain vasculature, rendering the task of fiber tracking more difficult. This observation provides converging evidence that the activated areas using ADC contrast are more closely coupled to the neuronal activity than those using BOLD contrast.

Brain↗

Binocular interactions in striate cortical neurons of cats reared with discordant visual inputs.

The postnatal development of cortical binocularity is known to be adversely affected by early abnormal visual experience. However, little information exists on how the signals from the two eyes are combined in individual cortical neurons of animals reared with early discordant binocular visual experience. Since this is a fundamental issue in understanding visual cortical development, we used extracellular single-unit recording methods to study binocular integration in striate cortical neurons of strabismic cats. Specifically, we measured the sensitivity of individual cells to the relative interocular spatial phase of dichoptically presented drifting sinusoidal gratings (i.e., to binocular retinal image disparity). Clear alterations in ocular dominance were observed in all strabismic subjects. Nevertheless, the majority of cortical neurons exhibited some form of binocular interactions when both eyes were stimulated together. The most prominent aspect of cortical physiology in the strabismic animals was the relatively high prevalence of suppressive binocular interactions. Suppression was most frequently found in kittens reared with 2 weeks of early optical dissociation and among adult cats that received 2 weeks of early optical dissociation and a prolonged recovery period. However, substantial excitatory binocular interactions were also maintained in these animals. With an extended period of interocular misalignment (3 or 8 months), all forms of binocular interactions, excitatory and suppressive, were drastically reduced and a greater number of neurons were truly monocular. Although the reduction in the strength of binocular interactions occurred in all units irrespective of their monocular spatial properties, the effect was more pronounced among those units tuned to higher spatial frequencies and this spatial-frequency-dependent effect was larger in the subjects receiving longer periods of binocular dissociation. The results suggest that the "breakdown" of cortical binocular properties in strabismic subjects is not an all-or-none process, and that suppressive binocular interactions may be closely associated with the abnormal binocular interactions exhibited by strabismic humans. Furthermore, our findings are consistent with the notion that cortical disparity-detecting mechanisms are spatial-frequency dependent and, thus, can be selectively altered depending on an animal's early visual experience.

Animals↗

Time-dependent effects of discrete spatial cues on the planning of directed movements.

The degree of preparation of a motor response varies with the information available regarding the response that will need to be executed and with the time provided to process that information. In experiment 1 we investigated the time-course of processing the information specified by discrete spatial cues regarding the upcoming target of directed movements. For this purpose we varied the number of cues that indicated the possible locations of the target and the duration of the cue period preceding the target. The results showed that the effects of processing the information provided by the cues developed progressively and stabilized after 0.2 s. In addition, the level of motor preparation reached was a function of number of cues. However, the effect of number of cues occurred even in the no cue period condition, i.e. when subjects could not have benefited from the information provided by the cues to prepare the response. Further analyses suggested the hypothesis that, in the no cue period condition, the effect of number of cues resulted from the cues acting as distractors (i.e., interference) whereas, with longer cue periods, the effect resulted from the motor preparatory process (i.e., facilitation). This hypothesis was tested in experiment 2 where the number of cues and the number of distractors were varied inversely. Cues and distractors were the same type of stimuli and differed only in their relation to the time of presentation of the target. Subjects performed in a directed response task and in a control detection task. It was predicted that the facilitatory effect of the cues and the interference effect of the distractors on the planning of the directed response would oppose each other and produce a non-monotonic change of RT across conditions. The results conformed to the prediction and, therefore, supported the hypothesis of independent effects of facilitation and interference. In addition, we found that the pattern of RT across conditions in the detection task differed radically with that in the directed response task. This result indicates that the time-dependent effects of cues and distractors are contingent on the type of motor response required in the task, and, in particular on the spatial requirement on the motor response.

Adult↗

The effect of spatial attention on contrast response functions in human visual cortex.

Previous electrophysiology data suggests that the modulation of neuronal firing by spatial attention depends on stimulus contrast, which has been described using either a multiplicative gain or a contrast-gain model. Here we measured the effect of spatial attention on contrast responses in humans using functional MRI. To our surprise, we found that the modulation of blood oxygenation level-dependent (BOLD) responses by spatial attention does not greatly depend on stimulus contrast in visual cortical areas tested [V1, V2, V3, and MT+ (middle temporal area)]. An additive model, rather than a multiplicative or contrast-gain model best describes the attentional modulations in V1. This inconsistency with previous single-unit electrophysiological data has implications for the population-based neuronal source of the BOLD signal.

Adult↗

Is impaired memory for spatial location in Parkinson's disease domain specific or dependent on 'strategic' processes?

Spatial memory has been found to be impaired in Parkinson's disease (PD). To determine the nature of the deficit, we compared the performance of'standard' levodopa-treated patients with PD to that of matched control subjects in different situations: (i) spatial versus verbal conditional associative learning; (ii) 'global' versus 'local' contextual encoding; (iii) pattern span and related supraspan learning. The relationship between dopaminergic depletion, which characterizes the disease, and the impaired memory processes was investigated by comparing the performance of 'de novo' not yet treated PD patients to that of matched control subjects. Both groups of PD patients were impaired in all situations requiring strategic processes, shared a decreased pattern span and had a normal visuospatial learning once the pattern span was taken into account. All these results suggest that the memory deficit for spatial location observed in PD results mainly from a disturbance of strategic processes and from decreased attentional resources, which may be due, at least in part, to the dopaminergic depletion and related striatofrontal dysfunction.

Aged↗

Representational momentum in spatial hearing does not depend on eye movements.

The perceived final position of a moving object usually seems to be displaced in the direction of motion. This displacement effect, termed representational momentum, has been reported for both visual and acoustic targets. This study investigated whether representational momentum in the auditory modality depends on oculomotor behavior during target presentation. In a dark anechoic environment, subjects localized the final position of a horizontally moving acoustic target (continuous noise) by using a hand pointer. Subjects were instructed to pursue the acoustic target with their eyes, to maintain central gaze direction, or to fixate a central visual fixation point. Forward displacements of the perceived final target position occurred irrespective of the eye-movement condition. This result is not consistent with previous findings in the visual modality indicating a reduction of forward displacement for continuously moving targets with fixation. It is suggested that factors other than oculomotor behavior are the source of representational momentum in spatial hearing.

Acoustic Stimulation↗

The early facilitatory effect of a peripheral spatially noninformative prime stimulus depends on target stimulus features.

We investigated the dependency of the early facilitatory effect of a prime stimulus (S1) on the physical characteristics of the target stimulus (S2). A go-no go reaction time paradigm was used. The S1 was a gray ring and the S2s were a white vertical line, a white horizontal line, a white cross and a white small ring, all inside a white ring with the same dimensions as the S1. S1 onset-S2 onset asynchrony was 100 ms. The stimuli appeared randomly in any one of the quadrants of a monitor screen. The S2 could occur at the same position as the S1 or at a different one. We observed a strong facilitatory effect when the vertical line or the horizontal line was the go stimulus and no effect when the cross was the go stimulus. These results show that the features of the target stimulus can be decisive for the appearance of the facilitatory effect of a peripheral spatially noninformative prime stimulus.

Adult↗

Dopamine depletion, stimulation or blockade in the rat disrupts spatial navigation and locomotion dependent upon beacon or distal cues.

Rats depleted of dopamine by intraventricular or nigrostriatal bundle 6-hydroxydopamine injection were compared with normal rats on acquisition and retention of place and cue navigation in the Morris swimming pool test and on a battery of sensorimotor tests. Rats with extensive bilateral dopamine depletions were able to swim vigorously, but were unable to acquire either the place or cue task. Rats with unilateral lesions, although impaired in the rate of acquisition were eventually able to learn both tasks to close to normal levels. Animals pretrained on the tasks prior to the lesions displayed retention deficits that were related to the extent of dopamine depletion: after extensive depletions, performance on both tasks deteriorated until successful navigation was abolished, whereas incomplete depletions impaired but did not abolish performance on either task. In separate groups of pretrained animals, both dopamine antagonists (haloperidol, alpha-flupenthixol) and agonists (apomorphine, metamphetamine) blocked performance on both place and cue tasks, although there were individual differences in sensitivity of the rats. Performance on the place task was more sensitive to disruption than the cue task both by the lesions and by haloperidol, alpha-flupenthixol or apormorphine but not by metamphetamine. On the sensorimotor tests dopamine-depleted rats were impaired at visual but not contact placing, they oriented weakly to snout touches and surfaces but not to distal stimuli, and they were akinetic on a number of tests of motor function but when wet they displayed as many grooming movements and groomed as long as did normal rats. The results suggest that dopamine depletion may impair spatial navigation by a disruption of their ability to use distal cues for guidance.

Animals↗

On the evolution of density dependent dispersal in a spatially structured population model.

A simple metapopulation lattice model of two competing phenotypes is presented, where one phenotype reacts more sensitively to overcrowding by migrating to neighbouring local habitats. The sensitivity is formulated by means of a threshold density of the subpopulations, above which dispersal is triggered off. If this threshold density is not very far from the local carrying capacity, an increased mobility provides benefits on the metapopulation level. At a surprisingly small difference between migrational triggering thresholds, the phenotype of larger mobility (or lower threshold) squeezes out the less mobile one from the whole system in a wide parameter range. Evolutionary considerations give an optimal threshold level for our model metapopulation.

Animals↗

Experience-dependent maturation of the spatial and temporal characteristics of the cell receptive fields in the kitten visual cortex.

The development of contrast sensitivity to spatial and temporal frequencies was studied in the visual cortex of 6-week-old kittens reared from birth in three conditions: normal, dark-reared (DR) and dark-reared after 6 h of visual experience. Receptive fields of cells recorded in area 17 were quantitatively analysed using drifting sine-wave gratings. Compared to the low values obtained in the DR kittens, we observed after 6 h of visual experience: (1) an adult-like detection of higher spatial frequencies, (2) an increase of contrast sensitivity at low temporal frequencies; (3) a shift of the cell optimum towards 3 Hz, all values close to the normal ones. Unlike the spatial frequency selectivity, contrast sensitivity and detection of higher temporal frequencies continue to develop with age and visual experience.

Animals↗

Hippocampally dependent and independent chronic spatial navigational deficits following parasagittal fluid percussion brain injury in the rat.

Previous reports have documented spatial navigational deficits following experimental traumatic brain injury (TBI), although the majority of the work to date has involved assessment at acute intervals following TBI, and has focused on tasks sensitive to hippocampal dysfunction. The present experiments were designed to investigate the chronic consequences of TBI, and the possible contribution of extrahippocampal dysfunction to TBI-induced spatial navigational deficits, in a moderate parasagittal fluid percussion TBI model. In Experiment 1, animals were pre-trained in a water maze, subjected to TBI or sham procedures, and re-evaluated in the water maze 48 h following the insult. Six to 8 weeks following TBI, the same animals were required to navigate to a different platform location. TBI animals exhibited significant deficits in retention of previously learned spatial information at the 48 h interval, and marginally impaired acquisition of a novel platform location during the chronic test sessions. In Experiment 2, animals were required to navigate to novel spatial locations using cued (to evaluate extrahippocampal function) as well as non-cued variants of the water maze task during the 8 week period following the insult. Injured animals exhibited deficits in both tasks which gradually diminished over the course of testing. The results of these experiments indicate that moderate TBI is accompanied by both retention and acquisition deficits, and that some of the navigational deficits observed in the water maze can be attributed to extrahippocampal damage. The possible recovery of spatial navigational ability following parasagittal TBI at moderate intensities is also discussed.

Acute Disease↗

Task-dependent strain difference of spatial learning in C57BL/6N and BALB/c mice.

In the present study, we used a dry maze task to assess the spatial learning ability of C57BL/6N and BALB/cA mice besides the water maze task. In Experiment 1, the performance of C57BL/6N and BALB/cA mice in the water maze task and dry maze task were investigated. In the former task, the mice had to learn the position of a hidden platform submerged below the water surface and they had to learn the position of a baited hole on the circular maze in the latter task. C57BL/6N mice showed significant learning in both maze tasks, whereas BALB/cA mice showed learning in a dry maze but not in water maze as reported before. In Experiment 2, a dry maze task was conducted on a circular open field which contained 16 holes arranged symmetrically and which was put on the same height as the surface of the water maze. In Experiment 2, BALB/cA mice showed significant improvement in latency and path length to reach the food hole. The poor performance of the BALB/cA in the water maze task may reflect a weak motivation, escaping from water, rather than the poor spatial memory in this strain.

Animals↗

Age and experience-dependent representational reorganization during spatial learning.

Previously, we found that aged rats showed a significant enhancement of hippocampal CA1 place cell spatial specificity, as well as a reduction of hilar place cell spatial specificity, during asymptote performance of a spatial memory task. Because such an age effect was not observed when animals performed a nonspatial task, the present study tested the hypothesis that the different patterns of spatial selectivity observed in memory and nonmemory tests reflected a redistribution of spatial representations that occurred in response to changing task demands. In the present experiment, after animals became familiar with the test environment and motor demands of performance on a radial maze, CA1 and hilar place cells were recorded as they learned a spatial memory task. CA1 place cells recorded from unimpaired old, but not impaired old or young, animals became more spatially selective as animals learned the task. Hilar spatial selectivity for both age groups was not significantly related to choice accuracy. These data support the hypothesis that at least a subpopulation of aged rats may benefit from reorganization of spatial representations in such a way that the normal age-related spatial learning deficit is attenuated.

Aging↗

A nonlinear spatially variant object-dependent system model for prediction of partial volume effects and scatter in PET.

Accurate quantitation of small lesions with positron emission tomography (PET) requires correction for the partial volume effect. Traditional methods that use Gaussian models of the PET system were found to be insufficient. A new approach that models the non-Gaussian object-dependent scatter was developed. The model consists of eight simple functions with a total of 24 parameters. Images of line and disk sources in circular and elliptical cylinders, and an anthropomorphic chest phantom were used to determine the parameter values. Empirical rules to determine these parameter values for various objects based on those for a reference object, a 21.5-cm circular cylinder, were also proposed. For seven spheroids and a 3.4-cm cylinder, pixel values predicted by the model were compared with the measured values. The model-to-measurement-ratio was 1.03+/-0.07 near the center of the spheroids and 0.99+/-0.03 near the center of the 3.4-cm cylinder. In comparison, the standard single Gaussian model had corresponding ratios of 1.27+/-0.09 and 1.24+/-0.03, respectively, and the corresponding ratios for a double Gaussian model were 1.13+/-0.09 and 1.05+/-0.01. Scatter fraction (28.5%) for a line source in the 21.5-cm cylinder was correctly estimated by our model. Because of scatter, we found that errors in the measurement of activity in spheroids with diameters from 0.6 to 3.4 cm were more significant than previously appreciated.

Algorithms↗

Spatial distribution and frequency dependence of arrhythmogenic vagal effects in canine atria.

INTRODUCTION: Prior studies in isolated canine atria demonstrated that acetylcholine-induced reentrant atrial fibrillation (AF) was triggered by multifocal activity in the area of normal impulse origin (sinus node-crista terminalis). The aim of this study was to investigate the activation sequence in AF induced by vagal stimulation (VS) in intact dog hearts. METHODS AND RESULTS: VS (10 to 50 Hz, 1 msec, 15 V, 5-sec trains) induced single or multiple atrial premature depolarizations (APDs), and/or AF in 8 of 10 open chest dogs. Occurrence of APDs and AF increased with increasing VS intensity. Epicardial mapping (254 unipolar electrodes) of both atria showed that APDs as a rule emerged from ectopic sites, often from the right atrial appendage. Activation mapping of the first 10 cycles of AF showed that only a small number (<3 to 4) of unstable reentrant circuits were possible at the same moment. Moreover, most sustained VS-induced AFs were accounted for by a single leading stable reentrant circuit that activated the remainder of the atria. CONCLUSION: (1) Occurrence of vagally induced APDs and AF increases with increasing frequency of VS. (2) VS-induced focal ectopic APDs are widely distributed over the atria. (3) A single APD can be sufficient for initiation of reentrant AF. (4) Despite its high rate of sustained AF, it may be maintained by single stable reentrant circuit. (5) The atrial septum can play an important role in both the initiation and the maintenance of VS-induced AF.

Animals↗