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Spatially specific expression of Hoxb4 is dependent on the ubiquitous transcription factor NFY.

Understanding how boundaries and domains of Hox gene expression are determined is critical to elucidating the means by which the embryo is patterned along the anteroposterior axis. We have performed a detailed analysis of the mouse Hoxb4 intron enhancer to identify upstream transcriptional regulators. In the context of an heterologous promoter, this enhancer can establish the appropriate anterior boundary of mesodermal expression but is unable to maintain it, showing that a specific interaction with its own promoter is important for maintenance. Enhancer function depends on a motif that contains overlapping binding sites for the transcription factors NFY and YY1. Specific mutations that either abolish or reduce NFY binding show that it is crucial for enhancer activity. The NFY/YY1 motif is reiterated in the Hoxb4 promoter and is known to be required for its activity. As these two factors are able to mediate opposing transcriptional effects by reorganizing the local chromatin environment, the relative levels of NFY and YY1 binding could represent a mechanism for balancing activation and repression of Hoxb4 through the same site.

Animals↗

The influence of spatial contrast on the frequency-dependent nature of vibration sensitivity.

Several stimulus configurations have been described for measuring the threshold for vibration perception. One such configuration, used primarily for screening for peripheral nervous system function, for example, consists of a matrix of 24 rows and 6 columns of tiny pins vibrating at 230 Hz, with the even rows of pins vibrating in opposite phase to the uneven rows. In order to determine which class of mechanoreceptors is being tested with such a stimulus, the frequency dependence of the threshold for vibration perception was measured with a similar stimulus configuration in a group of younger subjects and in a group of older subjects. Moreover, the stimulus configuration could be changed from opposite phase stimulation to equal phase stimulation, wherein all pins vibrated with equal phase. In the range above 160 Hz, it appeared that in younger subjects the threshold of the Pacinian receptor system was evaluated with both modes of stimulation, although the sensitivity for opposite phase stimulation was reduced relative to the sensitivity for equal phase stimulation. In the older subjects, equal phase stimulation also appeared to evaluate the Pacinian receptor system. However, with the opposite phase stimulation, the non-Pacinian receptors tended to be evaluated. Below 100 Hz, sensitivity was greater for opposite phase than for equal phase stimulation in both groups. Moreover, with both modes of stimulation, a sensitivity maximum at 40 Hz could be obtained, which was tentatively ascribed to the rapidly adapting class of mechanoreceptors.

Adult↗

[Asymmetry of the amplitude-temporal properties of visually-guided saccades in monkeys depending on the complexity of the spatial scheme of the visual stimulation].

The properties of visually-guided saccades were studied in three monkeys (Macaca rhesus). Traditional single-step GAP-OVERLAP temporal paradigms were used. Target stimuli were presented in accordance with two spatial stimulation schemes: (i) along the horizontal meridian (one-dimensional scheme) and (ii) within rectangle part of the visual field (two-dimensional scheme). We revealed asymmetric focuses of short- and long-latency saccades in the two-dimensional scheme of stimulation. The MANOVA revealed that the factor of dimensionality influenced saccadic latency to a greater extent than the factor of lateralization of stimuli (presenting in the right or left visual hemifields). Accuracy of saccades decreased with increasing in their eccentricity in both spatial schemes of stimulation.

Animals↗

Spatial summation determines the contrast response of displacement threshold hyperacuity.

The effect of line length on displacement threshold hyperacuity at various levels of contrast was investigated. At high contrasts there was no significant effect of line length, but as contrast was reduced thresholds for shorter line lengths increased rapidly. Thresholds at longer line lengths demonstrated a form of contrast saturation which differed from vernier acuity whose thresholds increased consistently with a reduction in contrast. As line length in the displacement threshold task was reduced, the amount of contrast saturation became less and displacement thresholds therefore resembled the contrast response of vernier acuity. Results are explained in terms of spatial summation along the length of the lines, the effects of which depend upon the spatial configuration of the hyperacuity stimulus under consideration.

Contrast Sensitivity↗

Spatial-frequency response of a photoreceptor and its wavelength dependence. I. Coherent sources.

The response of an isolated model foveal cone to a coherent sinusoidal intensity source is explored with use of the methods of photoreceptor optics. The dielectric waveguide model of a foveal cone that was previously used to explain the Stiles-Crawford effect and its wavelength dependence [Vision Res. 13, 1115 (1973)] is applied to photoreceptor excitation by coherent gratings with variable spatial frequency and light wavelength. The results indicate that the photoreceptors themselves contribute to visual acuity through a wavelength-dependent response at each spatial frequency. In particular, the isolated photoreceptor has a characteristic low-pass spatial-frequency-filter effect for wavelengths between 410 and 654 nm (where two waveguide modes are carried) and a flat response for wavelengths greater than 654 nm (the single-mode region).

Fovea Centralis↗

Impairments in spatial learning and memory: ethanol, allopregnanolone, and the hippocampus.

Acute ethanol administration impairs performance in many cognitive tasks that are dependent on hippocampal function. For example, acute ethanol administration produces dose-dependent impairments in spatial learning. Ethanol also decreases the spatial specificity of hippocampal place cells. Such findings raise the possibility that ethanol affects learning and memory by altering, either directly or indirectly, neuronal activity in the hippocampus and related structures. Acute ethanol administration induces a dose- and time-dependent increase in brain concentration of the neuroactive steroid allopregnanolone. Allopregnanolone is a potent GABAA receptor agonist and produces effects similar to the effects produced by ethanol. Blockade of de novo biosynthesis of allopregnanolone alters many of ethanol's effects including ethanol-induced suppression of spontaneous activity in medial septum/diagonal band of Broca neurons and hippocampal pyramidal neurons. These findings suggest that ethanol-induced increases in allopregnanolone levels might play a central role in the effects of acute ethanol on cognitive processing and hippocampal function. The impact of ethanol on spatial cognitive processing and hippocampal function will be reviewed. In addition, the possibility that ethanol-induced changes in neuroactive steroid levels contribute to the impact of ethanol on spatial learning and hippocampal function will be explored.

Animals↗

Dissociating visual attention and effector selection in spatial precuing tasks.

In this study the authors tested and rejected a recent proposal that response precuing effects depend on the spatial extent of the precues rather than on the number of response choices. Moreover, the authors tested and supported the hypothesis that the number of effectors in the response set is an important determinant of spatial precuing effects. Results of 4 experiments consistently showed that keypress responses generated a qualitatively different pattern of precuing effects than did pointing and detection responses. Together, the results establish a strong dissociation between planning pointing responses and planning keypress responses and suggest that precuing effects in 1-effector and multiple-effector visuomotor tasks are dominated by distinct and separate mechanisms, visual attention and effector selection, respectively.

Adolescent↗

Signal transfer from photoreceptors to bipolar cells in the retina of the tiger salamander.

Under conditions of dark-adaptation, in response to weak stimuli, the distal retina behaves as a linear system. During the process of voltage transfer from the rods to the bipolar cells the information encoded in the rod responses is spatially filtered. The spatial filtering is determined by the spatial properties of the receptive field of the bipolar cell. These, in turn, depend upon the spatial properties of three syncytia, those of the receptors, the horizontal cells and the bipolar cells themselves. The response of the bipolar cell to these weak stimuli is a linear difference of two components; a component generated by the receptive field center and a component generated by the receptive field surround. The receptive field surround is misnamed since it extends throughout the receptive field center and contributes to the response of the bipolar cell to stimuli located anywhere within the receptive field. The receptive field surround has the spatial properties that would be expected if it were generated by an input from the horizontal cells to the receptive field center of the bipolar cell. The cellular pathway mediating this input remains unclear though we have evidence that it involves, at least in part, a feedforward pathway from horizontal cells to bipolar cells. If a feedback pathway also exists it is not mediated by the GABAA synapse on the synaptic terminals of the cones.

Animals↗

Spatial localization after excision of human auditory cortex.

Neurophysiological and animal ablation studies concur that primary auditory cortex is necessary for computation of the spatial coordinates of a sound source. Human studies have reported conflicting findings but have often suffered from inadequate psychophysical measures and/or poor lesion localization. We tested patients with unilateral temporal lobe excisions either encroaching on or sparing Heschl's gyrus (HG), quantifying lesion extent using anatomical magnetic resonance imaging measures. Subjects performed two tasks. In the localization task, they heard single clicks in a free-field spatial array subtending 180 degrees of azimuth and indicated the perceived location with a laser pointer. In the discrimination task, two clicks were presented, and subjects indicated if they were in the same or different position. As a group, patients with right temporal excision, either encroaching onto HG or not, were significantly impaired in both hemifields in both tasks, although this was not true for all individuals. Patients with left temporal resections generally performed normally, although some of the patients with left HG excision showed impaired performance bilaterally, especially in the discrimination task. This pattern stands in marked contrast to previous studies showing significant preservation of localization in hemispherectomized patients. We conclude that (1) contrary to hypotheses derived from animal studies, human auditory spatial processes are dependent primarily on cortical areas within right superior temporal cortex, which encompass both spatial hemifields; (2) functional reorganization may not take place after restricted focal damage but only after more extensive early damage; and (3) the existence of individual differences likely illustrates differential patterns of functional lateralization and/or recovery.

Acoustic Stimulation↗

Direct cytochemical localization of catalytic subunits dissociated from cAMP-dependent protein kinase in Reuber H-35 hepatoma cells. II. Temporal and spatial kinetics.

The activation of cyclic AMP-dependent protein kinase has been found to be the predominant mode by which cyclic AMP (cAMP) leads to alterations of a large variety of cellular functions. The activation of the kinase results in the release of the catalytic subunit which as the free enzyme possesses phosphotransferase activity for a variety of specific protein substrates. Using a sensitive and specific cytofluorometric technique we monitored the appearance of free catalytic subunit in Reuber H35 hepatoma cells in culture after incubation with N6-1'-O-dibutyryl-cyclic AMP (DBcAMP), 8-bromoadenosine-3':5'-cyclic monophosphate (8-BrcAMP), and glucagon. The cytochemical method employs the heat-stable inhibitor of the free catalytic subunit which has been conjugated to fluorescein isothiocyanate (F:PKI) and was validated as described in the companion paper (Fletcher and Byus. 1982. J. Cell Biol. 93:719-726). Here we studied the temporal and spatial kinetics of the free catalytic subunit following activation of cAMP-dependent protein kinase by increasing concentrations of DBcAMP,8-BrcAMP, and glucagon. Under similar conditions protein kinase activation was also assessed biochemically in H35 cell supernatants by assaying the protein kinase activity ratio. Incubation of the hepatoma cells with DBcAMP (0.1 mM) led to an increase in the activity ratio from 0.2 in control cultures to a value of nearly 1.0 within a 1- to 2-h period. During this same period using the F:PKI probe, a significant increase in cytoplasmic and nucleolar fluorescence indicative of the release of the free catalytic subunit was coincidentally observed. In contrast to the rapid appearance of catalytic subunit in the cytoplasm and nucleolus of the cell within 5-15 min of the addition of DBcAMP, discernible nucleoplasmic fluorescence did not occur until after 1 h. H35 cell cultures incubated with 8-BrcAMP (0.01-1.0 mM) exhibited a more rapid activation of the protein kinase measured cytochemically compared to the cells treated with DBcAMP. Cultures incubated with 8-BrcAMP had significantly increased cytoplasmic and nucleolar fluorescence compared to unstimulated cells within 1 min of the addition of the analogue and reached a maximal level within 15 min. By employing a microspectrophotometer a distinct dose-dependent increase in cellular fluorescence (i.e., free catalytic subunit) was observed as the concentration of 8-BrcAMP was increased from 0.01 to 1.0 mM at 1, 5, 15, and 60 min following stimulation. The addition of glucagon (10(-6) M) to the culture also led to the activation of cAMP-dependent protein kinase as determined by an increase in the activity ratio. This increase was paralleled throughout the incubation period by a marked elevation in cytoplasmic and nucleolar fluorescence. The results reported herein suggest that both cyclic nucleotide analogues and a polypeptide hormone lead to the activation of cAMP-dependent protein kinase in similar intracellular compartments in Reuber H35 hepatoma cells...

Adenosine Monophosphate↗

Circuits for local and global signal integration in primary visual cortex.

Contrast-dependent changes in spatial summation and contextual modulation of primary visual cortex (V1) neuron responses to stimulation of their receptive field reveal long-distance integration of visual signals within V1, well beyond the classical receptive field (cRF) of single neurons. To identify the cortical circuits mediating these long-distance computations, we have used a combination of anatomical and physiological recording methods to determine the spatial scale and retinotopic logic of intra-areal V1 horizontal connections and inter-areal feedback connections to V1. We have then compared the spatial scales of these connectional systems to the spatial dimensions of the cRF, spatial summation field (SF), and modulatory surround field of macaque V1 neurons. We find that monosynaptic horizontal connections within area V1 are of an appropriate spatial scale to mediate interactions within the SF of V1 neurons and to underlie contrast-dependent changes in SF size. Contrary to common beliefs, these connections cannot fully account for the dimensions of the surround field. The spatial scale of feedback circuits from extrastriate cortex to V1 is, instead, commensurate with the full spatial range of center-surround interactions. Thus these connections could represent an anatomical substrate for contextual modulation and global-to-local integration of visual signals. Feedback projections connect corresponding and equal-sized regions of the visual field in striate and extrastriate cortices and cover anisotropic parts of visual space, unlike V1 horizontal connections that are isotropic in the macaque. V1 isotropic connectivity demonstrates that anisotropic horizontal connections are not necessary to generate orientation selectivity. Anisotropic feedback connections may play a role in contour completion.

Animals↗

Spatial-frequency characteristics of neurones of area 18 in the cat: dependence on the velocity of the visual stimulus.

The spatial and temporal response properties of neurones of areas 17 and 18 were studied in single units (165) of anaesthetized and paralysed cats. The visual stimuli were drifting or alternating gratings. We confirmed and extended the observation by Tolhurst & Movshon (1975) showing that the spatial-frequency characteristics of neurones of area 17 are largely independent of the temporal parameters of drifting or alternating gratings. The spatial-frequency tuning curves of neurones of area 18 shift along the spatial-frequency axis when the velocity or the temporal frequency of the drifting grating are changed. The effect of an increase either of velocity or temporal frequency is to shift the cell spatial-frequency tuning curve down the spatial-frequency scale, keeping relatively constant the strength and band width of the response. The spatial-frequency tuning curves of neurones of area 18 do not show this temporal-frequency-dependent phenomenon when the stimuli are gratings alternated in phase. In this case neurones of areas 17 and 18 show a similar behaviour. The response properties of neurones of area 18 are compared with recent psychophysical results obtained in similar experimental conditions. The hypothesis is advanced that both areas 17 and 18 are devoted to the processing of spatial information. Area 17 would be responsible for the processing of patterns in stationary or quasi-stationary situations while area 18 would be responsible for that of patterns moving at high velocities.

Animals↗

A unified functional/anatomic substrate for circus movement atrial flutter: activation and refractory patterns in the canine right atrial enlargement model.

OBJECTIVES: This study was designed to test the concept of a functional/anatomic interaction in a canine model of reentry based on right atrial enlargement and to elucidate the electrophysiologic basis for functional conduction block. BACKGROUND: The monotonic feature of atrial flutter suggests a uniform substrate for the arrhythmia. Atrial flutter in the sterile pericarditis model is due to single-loop circus movement around a functional or a functional/anatomic obstacle near the atrioventricular (AV) ring. Sustained circus movement requires a critical interaction of a functional arc of block, a natural obstacle, the AV ring and a zone of slow conduction. The location of the inferior vena cava predisposes the lower right atrium to single-loop reentry. METHODS: In 11 dogs with right atrial enlargement, 127 bipolar epicardial electrograms were obtained during atrial flutter. For correlation of activation and refractory maps, the effective refractory period under each electrode was determined using the extrastimulus technique. RESULTS: Atrial flutter was due to single-loop reentry around functional arcs of block near the AV ring (n = 2) or around functional/anatomic obstacles (n = 8) involving the inferior vena cava. A slow zone was located between the arc and the AV ring and between the inferior vena cava and AV ring, respectively. During initiation, the arc joined the AV ring, forcing activation to proceed around the free end of the arc before breaking through the arc near the AV ring. Arrhythmia termination required the arc of block to rejoin the AV ring. Inducibility of sustained atrial flutter was associated with a marked spatial dispersion of refractoriness. The configuration of the functional arc of block was critically dependent on the spatial pattern of refractoriness. CONCLUSIONS: Atrial flutter requires a similar functional or functional/anatomic substrate independent of the underlying etiology. The spatial distribution of refractoriness in enlarged canine atria provides an adequate substrate for the development of functional conduction block.

Animals↗

Cortical dynamics of lateral inhibition: metacontrast masking.

The dynamic properties of a neural network model of visual perception, called the boundary contour system, explain characteristics of metacontrast visual masking. Computer simulations of the model, with a single set of parameters, demonstrate that it accounts for 9 key properties of metacontrast masking: Metacontrast masking is strongest at positive stimulus onset asynchronies (SOAs); decreasing target luminance changes the shape of the masking curve; increasing target duration weakens masking; masking effects weaken with spatial separation; increasing mask duration leads to stronger masking at shorter SOAs; masking strength depends on the amount and distribution of contour in the mask; a second mask can disinhibit the masking of the target; such disinhibition depends on the SOA of the 2 masks; and such disinhibition depends on the spatial separation of the 2 masks. No other theory provides a unified explanation of these data sets. Additionally, the model suggests a new analysis of data related to the SOA law and makes several testable predictions.

Attention↗

Spatial spread of in-field afferent inhibition in the cat's spinocervical tract.

1. Extracellular microelectrode recordings were made from twenty-three spinocervical tract (SCT) cells in the lumbar spinal cord of cats anaesthetized with chloralose and paralysed with gallamine triethiodide. Excitation and inhibition of the cells were elicited by applying small brief (4 mN, 60 ms) localized jets of air to the clipped hair in and around the receptive fields. 2. Receptive field extents ranged from 40 to 180 mm. Excitation occurred in the period 30-130 ms after the start of the stimulus, and in-field afferent inhibition from 130 ms up to 700 ms or more. The inhibition was manifest as a reduction in background discharge and as a reduction in responsiveness to a test stimulus which followed a conditioning stimulus. 3. When the conditioning stimulus was spatially separated from the test stimulus, the degrees of in-field afferent inhibition depended on the spatial separation, even when both were within the excitatory receptive field. The spatial spread of in-field afferent inhibition was limited to 100 mm or less. 4. In two units only, afferent inhibition was produced from a narrow strip just outside the excitatory receptive field. In the other units, it could only be produced from within the excitatory receptive field. 5. The results suggest that the inhibitory input to SCT cells is organized in subdomains no more than 100 mm across, which may correspond to the receptive fields of interneurones between the primary afferent fibres and the SCT cells.

Afferent Pathways↗

[Dependence of "macroscopic fluctuations" from cosmophysical factors. Spatial anisotropy].

It was shown in experiments with collimators that the changes with time in the shape of histograms constructed from the measurements of the alpha-activity of 239Pu microsamples depend on the direction of the flow alpha-particles. If the flow of alpha-particles was directed to the Polar Star, the dependence of the probability of the realization of histograms of similar shape on time disappeared. The measurements of alpha-particle flows directed to the East and West revealed a high probability of the repeated realization of histograms of similar shape in 1436 min, i.e., in a sederal day. A comparison of "west" and "east" histograms showed a high probability of the realization of similar "west" histograms 718 min (half a sideral day) later than "east" histograms. The results suggest that the shape of histograms depends on the pattern of the starry sky and the space-time inhomogeneity corresponding to this pattern.

Plutonium↗