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At least 631 records · Page 35

Callosally projecting neurons in the macaque monkey V1/V2 border are enriched in nonphosphorylated neurofilament protein

Previous immunohistochemical studies combined with retrograde tracing in macaque monkeys have demonstrated that corticocortical projections can be differentiated by their content of neurofilament protein. The present study analyzed the distribution of nonphosphorylated neurofilament protein in callosally projecting neurons located at the V1/V2 border. All of the retrogradely labeled neurons were located in layer III at the V1/V2 border and at an immediately adjacent zone of area V2. A quantitative analysis showed that the vast majority (almost 95%) of these interhemispheric projection neurons contain neurofilament protein immunoreactivity. This observation differs from data obtained in other sets of callosal connections, including homotypical interhemispheric projections in the prefrontal, temporal, and parietal association cortices, that were found to contain uniformly low proportions of neurofilament protein-immunoreactive neurons. Comparably, highly variable proportions of neurofilament protein-containing neurons have been reported in intrahemispheric corticocortical pathways, including feedforward and feedback visual connections. These results indicate that neurofilament protein is a prominent neurochemical feature that identifies a particular population of interhemispheric projection neurons at the V1/V2 border and suggest that this biochemical attribute may be critical for the function of this subset of callosal neurons.

Non-NASA Center↗

Yaw sensory rearrangement alters pitch vestibulo-ocular reflex responses

Ten male subjects underwent two types of adaptation paradigm designed either to enhance or to attenuate the gain of the canal-ocular reflex (COR), before undergoing otolith-ocular reflex (OOR) testing with constant velocity, earth horizontal axis and pitch rotation. The adaptation paradigm paired a 0.2 Hz sinusoidal rotation about an earth vertical axis with a 0.2 Hz optokinetic stimulus that was deliberately mismatched in peak velocity or phase and was designed to produce short-term changes in the COR. Preadaptation and postadaptation OOR tests occurred at a constant velocity of 60 degrees/sec in the dark and produced a modulation component of the slow phase velocity with a frequency of 0.16 Hz due to otolithic stimulation by the sinusoidally changing gravity vector. Of the seven subjects who showed enhancement of the COR gain, six also showed enhancement of the OOR modulation component. Of the seven subjects who showed attenuation of the COR gain, five also showed attenuation of the OOR modulation component. The probability that these two cross-axis adaptation effects would occur by chance is less than 0.02. This suggests that visual-vestibular conditioning of the yaw axis COR also induced changes in the pitch axis OOR. We thus postulate that the central nervous system pathways that process horizontal canal yaw stimuli have elements in common with those processing otolithic stimuli about the pitch axis.

NASA Discipline Neuroscience↗

Combined influences of gravitoinertial force level and visual field pitch on visually perceived eye level

Psychophysical measurements of the level at which observers set a small visual target so as to appear at eye level (VPEL) were made on 13 subjects in 1.0 g and 1.5 g environments in the Graybiel Laboratory rotating room while they viewed a pitched visual field or while in total darkness. The gravitoinertial force was parallel to the z-axis of the head and body during the measurements. The visual field consisted of two 58 degrees high, luminous, pitched-from-vertical, bilaterally symmetric, parallel lines, viewed in otherwise total darkness. The lines were horizontally separated by 53 degrees and presented at each of 7 angles of pitch ranging from 30 degrees with the top of the visual field turned away from the subject (top backward) to 30 degrees with the top turned toward the subject (top forward). At 1.5 g, VPEL changed linearly with the pitch of the 2-line stimulus and was depressed with top backward pitch and elevated with top forward pitch as had been reported previously at 1.0 g (1,2); however, the slopes of the VPEL-vs-pitch functions at 1.0 g and 1.5 g were indistinguishable. As reported previously also (3,4), the VPEL in darkness was considerably lower at 1.5 g than at 1.0 g; however, although the y-intercept of the VPEL-vs-pitch function in the presence of the 2-line visual field (visual field erect) was also lower at 1.5 g than at 1.0 g as it was in darkness, the G-related difference was significantly attenuated by the presence of the visual field. The quantitative characteristics of the results are consistent with a model in which VPEL is treated as a consequence of an algebraic weighted average or a vector sum of visual and nonvisual influences although the two combining rules lead to fits that are equally good.

Non-NASA Center↗

Kinematic principles of primate rotational vestibulo-ocular reflex. II. Gravity-dependent modulation of primary eye position

The kinematic constraints of three-dimensional eye positions were investigated in rhesus monkeys during passive head and body rotations relative to gravity. We studied fast and slow phase components of the vestibulo-ocular reflex (VOR) elicited by constant-velocity yaw rotations and sinusoidal oscillations about an earth-horizontal axis. We found that the spatial orientation of both fast and slow phase eye positions could be described locally by a planar surface with torsional variation of <2.0 +/- 0.4 degrees (displacement planes) that systematically rotated and/or shifted relative to Listing's plane. In supine/prone positions, displacement planes pitched forward/backward; in left/right ear-down positions, displacement planes were parallel shifted along the positive/negative torsional axis. Dynamically changing primary eye positions were computed from displacement planes. Torsional and vertical components of primary eye position modulated as a sinusoidal function of head orientation in space. The torsional component was maximal in ear-down positions and approximately zero in supine/prone orientations. The opposite was observed for the vertical component. Modulation of the horizontal component of primary eye position exhibited a more complex dependence. In contrast to the torsional component, which was relatively independent of rotational speed, modulation of the vertical and horizontal components of primary position depended strongly on the speed of head rotation (i.e., on the frequency of oscillation of the gravity vector component): the faster the head rotated relative to gravity, the larger was the modulation. Corresponding results were obtained when a model based on a sinusoidal dependence of instantaneous displacement planes (and primary eye position) on head orientation relative to gravity was fitted to VOR fast phase positions. When VOR fast phase positions were expressed relative to primary eye position estimated from the model fits, they were confined approximately to a single plane with a small torsional standard deviation ( approximately 1.4-2.6 degrees). This reduced torsional variation was in contrast to the large torsional spread (well >10-15 degrees ) of fast phase positions when expressed relative to Listing's plane. We conclude that primary eye position depends dynamically on head orientation relative to space rather than being fixed to the head. It defines a gravity-dependent coordinate system relative to which the torsional variability of eye positions is minimized even when the head is moved passively and vestibulo-ocular reflexes are evoked. In this general sense, Listing's law is preserved with respect to an otolith-controlled reference system that is defined dynamically by gravity.

NASA Discipline Neuroscience↗

Kinematic principles of primate rotational vestibulo-ocular reflex. I. Spatial organization of fast phase velocity axes

The spatial organization of fast phase velocity vectors of the vestibulo-ocular reflex (VOR) was studied in rhesus monkeys during yaw rotations about an earth-horizontal axis that changed continuously the orientation of the head relative to gravity ("barbecue spit" rotation). In addition to a velocity component parallel to the rotation axis, fast phases also exhibited a velocity component that invariably was oriented along the momentary direction of gravity. As the head rotated through supine and prone positions, torsional components of fast phase velocity axes became prominent. Similarly, as the head rotated through left and right ear-down positions, fast phase velocity axes exhibited prominent vertical components. The larger the speed of head rotation the greater the magnitude of this fast phase component, which was collinear with gravity. The main sequence properties of VOR fast phases were independent of head position. However, peak amplitude as well as peak velocity of fast phases were both modulated as a function of head orientation, exhibiting a minimum in prone position. The results suggest that the fast phases of vestibulo-ocular reflexes not only redirect gaze and reposition the eye in the direction of head motion but also reorient the eye with respect to earth-vertical when the head moves relative to gravity. As further elaborated in the companion paper, the underlying mechanism could be described as a dynamic, gravity-dependent modulation of the coordinates of ocular rotations relative to the head.

Non-NASA Center↗

Life and death of neurons in the aging brain

Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.

Review, Tutorial↗

Cortical neuronal cytoskeletal changes associated with FIV infection

HIV-1 infection is often complicated by central nervous system (CNS) dysfunction. Degenerative neuronal changes as well as neuronal loss have been documented in individuals with AIDS. Feline immunodeficiency virus (FIV) infection of cats provides a model for both the immune and the central nervous system manifestations of HIV infection of humans. In this study we have examined neurons in the frontal cortex of feline immunodeficiency virus-infected cats and controls for immunoreactivity with SMI 32, an antibody recognizing a non-phosphorylated epitope on neurofilaments. We noted a significant increase in the number of immunoreactive pyramidal cells in infected animals compared to controls. The changes seen in the neuronal cytoskeleton as a consequence of the inoculation with FIV were similar to those seen in humans undergoing the normal aging process as well as those suffering from neurological diseases, including Alzheimer's and dementia pugilistica. The changes we noted in the feline brain were also similar to that reported in animals with traumatic injuries or with spontaneously occurring or induced motor neuron diseases, suggesting that the increase in reactivity represents a deleterious effect of FIV on the central nervous system.

Non-NASA Center↗

Structural and functional analyses of human cerebral cortex using a surface-based atlas

We have analyzed the geometry, geography, and functional organization of human cerebral cortex using surface reconstructions and cortical flat maps of the left and right hemispheres generated from a digital atlas (the Visible Man). The total surface area of the reconstructed Visible Man neocortex is 1570 cm2 (both hemispheres), approximately 70% of which is buried in sulci. By linking the Visible Man cerebrum to the Talairach stereotaxic coordinate space, the locations of activation foci reported in neuroimaging studies can be readily visualized in relation to the cortical surface. The associated spatial uncertainty was empirically shown to have a radius in three dimensions of approximately 10 mm. Application of this approach to studies of visual cortex reveals the overall patterns of activation associated with different aspects of visual function and the relationship of these patterns to topographically organized visual areas. Our analysis supports a distinction between an anterior region in ventral occipito-temporal cortex that is selectively involved in form processing and a more posterior region (in or near areas VP and V4v) involved in both form and color processing. Foci associated with motion processing are mainly concentrated in a region along the occipito-temporal junction, the ventral portion of which overlaps with foci also implicated in form processing. Comparisons between flat maps of human and macaque monkey cerebral cortex indicate significant differences as well as many similarities in the relative sizes and positions of cortical regions known or suspected to be homologous in the two species.

NASA Discipline Neuroscience↗

Evidence for the involvement of carbonic anhydrase and urease in calcium carbonate formation in the gravity-sensing organ of Aplysia californica

To better understand the mechanisms that could modulate the formation of otoconia, calcium carbonate granules in the inner ear of vertebrate species, we examined statoconia formation in the gravity-sensing organ, the statocyst, of the gastropod mollusk Aplysia californica using an in vitro organ culture model. We determined the type of calcium carbonate present in the statoconia and investigated the role of carbonic anhydrase (CA) and urease in regulating statocyst pH as well as the role of protein synthesis and urease in statoconia production and homeostasis in vitro. The type of mineral present in statoconia was found to be aragonitic calcium carbonate. When the CA inhibitor, acetazolamide (AZ), was added to cultures of statocysts, the pH initially (30 min) increased and then decreased. The urease inhibitor, acetohydroxamic acid (AHA), decreased statocyst pH. Simultaneous addition of AZ and AHA caused a decrease in pH. Inhibition of urease activity also reduced total statoconia number, but had no effect on statoconia volume. Inhibition of protein synthesis reduced statoconia production and increased statoconia volume. In a previous study, inhibition of CA was shown to decrease statoconia production. Taken together, these data show that urease and CA play a role in regulating statocyst pH and the formation and maintenance of statoconia. CA produces carbonate ion for calcium carbonate formation and urease neutralizes the acid formed due to CA action, by production of ammonia.

Non-NASA Center↗

Calbindin and parvalbumin are early markers of non-mitotically regenerating hair cells in the bullfrog vestibular otolith organs

Earlier studies have demonstrated hair cell regeneration in the absence of cell proliferation, and suggested that supporting cells could phenotypically convert into hair cells following hair cell loss. Because calcium-binding proteins are involved in gene up-regulation, cell growth, and cell differentiation, we wished to determine if these proteins were up-regulated in scar formations and regenerating hair cells following gentamicin treatment. Calbindin and parvalbumin immunolabeling was examined in control or gentamicin-treated (GT) bullfrog saccular and utricular explants cultured for 3 days in amphibian culture medium or amphibian culture medium supplemented with aphidicolin, a blocker of nuclear DNA replication in eukaryotic cells. In control cultures, calbindin and parvalbumin immunolabeled the hair bundles and, less intensely, the cell bodies of mature hair cells. In GT or mitotically-blocked GT (MBGT) cultures, calbindin and parvalbumin immunolabeling was also seen in the hair bundles, cuticular plates, and cell bodies of hair cells with immature hair bundles. Thus, these antigens were useful markers for both normal and regenerating hair cells. Supporting cell immunolabeling was not seen in control cultures nor in the majority of supporting cells in GT cultures. In MBGT cultures, calbindin and parvalbumin immunolabeling was up-regulated in the cytosol of single supporting cells participating in scar formations and in supporting cells with hair cell-like characteristics. These data provide further evidence that non-mitotic hair cell regeneration in cultures can be accomplished by the conversion of supporting cells into hair cells.

Non-NASA Center↗

The role of reafference in recalibration of limb movement control and locomotion

The reafference model has frequently been used to explain spatial constancy during eye and head movements. We have found that its basic concepts also form part of the information processing necessary for the control and recalibration of reaching movements. Reaching was studied in a novel force environment--a rotating room that creates centripetal forces of the type that could someday substitute for gravity in space flight, and Coriolis forces which are side effects of rotation. We found that inertial, noncontacting Coriolis forces deviate the path and endpoint of reaching movements, a finding that shows the inadequacy of equilibrium position models of movement control. Repeated movements in the rotating room quickly lead to normal movement patterns and to a failure to perceive the perturbing forces. The first movements made after rotation stops, without Coriolis forces present, show mirror-image deviations and evoke perception of a perturbing force even though none is present. These patterns of sensorimotor control and adaptation can largely be explained on the basis of comparisons of efference copy, reafferent muscle spindle, and cutaneous mechanoreceptor signals. We also describe experiments on human locomotion using an apparatus similar to that which Mittelstaedt used to study the optomotor response of the Eristalis fly. These results show that the reafference principle relates as well to the perception of the forces acting on and exerted by the body during voluntary locomotion.

NASA Discipline Neuroscience↗

Saccule contribution to immediate early gene induction in the gerbil brainstem with posterior canal galvanic or hypergravity stimulation

Immunolabeling patterns of the immediate early gene-related protein Fos in the gerbil brainstem were studied following stimulation of the sacculus by both hypergravity and galvanic stimulation. Head-restrained, alert animals were exposed to a prolonged (1 h) inertial vector of 2 G (19.6 m/s2) head acceleration directed in a dorso-ventral head axis to maximally stimulate the sacculus. Fos-defined immunoreactivity was quantified, and the results compared to a control group. The hypergravity stimulus produced Fos immunolabeling in the dorsomedial cell column (dmcc) of the inferior olive independently of other subnuclei. Similar dmcc labeling was induced by a 30 min galvanic stimulus of up to -100 microA applied through a stimulating electrode placed unilaterally on the bony labyrinth overlying the posterior canal (PC). The pattern of vestibular afferent firing activity induced by this galvanic stimulus was quantified in anesthetized gerbils by simultaneously recording from Scarpa's ganglion. Only saccular and PC afferent neurons exhibited increases in average firing rates of 200-300%, suggesting a pattern of current spread involving only PC and saccular afferent neurons at this level of stimulation. These results suggest that alteration in saccular afferent firing rates are sufficient to induce Fos-defined genomic activation of the dmcc, and lend further evidence to the existence of a functional vestibulo-olivary-cerebellar pathway of adaptation to novel gravito-inertial environments.

NASA Discipline Neuroscience↗

Targeted gene expression without a tissue-specific promoter: creating mosaic embryos using laser-induced single-cell heat shock

We have developed a method to target gene expression in the Drosophila embryo to a specific cell without having a promoter that directs expression in that particular cell. Using a digitally enhanced imaging system to identify single cells within the living embryo, we apply a heat shock to each cell individually by using a laser microbeam. A 1- to 2-min laser treatment is sufficient to induce a heat-shock response but is not lethal to the heat-shocked cells. Induction of heat shock was measured in a variety of cell types, including neurons and somatic muscles, by the expression of beta-galactosidase from an hsp26-lacZ reporter construct or by expression of a UAS target gene after induction of hsGAL4. We discuss the applicability of this technique to ectopic gene expression studies, lineage tracing, gene inactivation studies, and studies of cells in vitro. Laser heat shock is a versatile technique that can be adapted for use in a variety of research organisms and is useful for any studies in which it is desirable to express a given gene in only a distinct cell or clone of cells, either transiently or constitutively, at a time point of choice.

Non-NASA Center↗

Light microscopic image analysis system to quantify immunoreactive terminal area apposed to nerve cells

The present report describes a desktop computer-based method for the quantitative assessment of the area occupied by immunoreactive terminals in close apposition to nerve cells in relation to the perimeter of the cell soma. This method is based on Fast Fourier Transform (FFT) routines incorporated in NIH-Image public domain software. Pyramidal cells of layer V of the somatosensory cortex outlined by GABA immunolabeled terminals were chosen for our analysis. A Leitz Diaplan light microscope was employed for the visualization of the sections. A Sierra Scientific Model 4030 CCD camera was used to capture the images into a Macintosh Centris 650 computer. After preprocessing, filtering was performed on the power spectrum in the frequency domain produced by the FFT operation. An inverse FFT with filter procedure was employed to restore the images to the spatial domain. Pasting of the original image to the transformed one using a Boolean logic operation called 'AND'ing produced an image with the terminals enhanced. This procedure allowed the creation of a binary image using a well-defined threshold of 128. Thus, the terminal area appears in black against a white background. This methodology provides an objective means of measurement of area by counting the total number of pixels occupied by immunoreactive terminals in light microscopic sections in which the difficulties of labeling intensity, size, shape and numerical density of terminals are avoided.

Non-NASA Center↗

Short latency vestibular evoked potentials in the Japanese quail (Coturnix coturnix japonica)

Short-latency vestibular-evoked potentials to pulsed linear acceleration were characterized in the quail. Responses occurred within 8 ms following the onset of stimuli and were composed of a series of positive and negative peaks. The latencies and amplitudes of the first four peaks were quantitatively characterized. Mean latencies at 1.0 g ms-1 ranged from 1265 +/- 208 microseconds (P1, N = 18) to 4802 +/- 441 microseconds (N4, N = 13). Amplitudes ranged from 3.72 +/- 1.51 microV (P1/N1, N = 18) to 1.49 +/- 0.77 microV (P3/N3, N = 16). Latency-intensity (LI) slopes ranged from -38.7 +/- 7.3 microseconds dB-1 (P1, N = 18) to -71.6 +/- 21.9 microseconds dB-1 (N3, N = 15) and amplitude-intensity (AI) slopes ranged from 0.20 +/- 0.08 microV dB-1 (P1/N1, N = 18) to 0.07 +/- 0.04 microV dB-1 (P3/N3, N = 11). The mean response threshold across all animals was -21.83 +/- 3.34 dB re: 1.0 g ms-1 (N = 18). Responses remained after cochlear extirpation showing that they could not depend critically on cochlear activity. Responses were eliminated by destruction of the vestibular end organs, thus showing that responses depended critically and specifically on the vestibular system. The results demonstrate that the responses are vestibular and the findings provide a scientific basis for using vestibular responses to evaluate vestibular function through ontogeny and senescence in the quail.

NASA Discipline Neuroscience↗

The effect of optokinetic stimulation on daytime sleepiness

This study examined the effect of optokinetic stimulation on objective sleepiness, as measured by the Multiple Sleep Latency Test (MSLT). The Nightcap, a portable sleep monitor, was used in a novel way to perform MSLTs, as well as record sleep in the home. Subjects wore the Nightcap for seven consecutive nights. On days 3 and 5 of the protocol, subjects came into the lab for an MSLT. On the experimental day, subjects underwent 10 minutes optokinetic stimulation (OKS), resulting in moderate motion sickness prior to each MSLT trial. Although subjects in the OKS condition reported significantly more drowsiness than controls, this did not result in significantly reduced sleep latencies.

NASA Discipline Neuroscience↗

Contrast affects flicker and speed perception differently

We have previously shown that contrast affects speed perception, with lower-contrast, drifting gratings perceived as moving slower. In a recent study, we examined the implications of this result on models of speed perception that use the amplitude of the response of linear spatio-temporal filters to determine speed. In this study, we investigate whether the contrast dependence of speed can be understood within the context of models in which speed estimation is made using the temporal frequency of the response of linear spatio-temporal filters. We measured the effect of contrast on flicker perception and found that contrast manipulations produce opposite effects on perceived drift rate and perceived flicker rate, i.e., reducing contrast increases the apparent temporal frequency of counterphase modulated gratings. This finding argues that, if a temporal frequency-based algorithm underlies speed perception, either flicker and speed perception must not be based on the output of the same mechanism or contrast effects on perceived spatial frequency reconcile the disparate effects observed for perceived temporal frequency and speed.

NASA Center ARC↗

Postural perturbations: new insights for treatment of balance disorders

This article reviews the neural control of posture as understood through studies of automatic responses to mechanical perturbations. Recent studies of responses to postural perturbations have provided a new view of how postural stability is controlled, and this view has profound implications for physical therapy practice. We discuss the implications for rehabilitation of balance disorders and demonstrate how an understanding of the specific systems underlying postural control can help to focus and enrich our therapeutic approaches. By understanding the basic systems underlying control of balance, such as strategy selection, rapid latencies, coordinated temporal spatial patterns, force control, and context-specific adaptations, therapists can focus their treatment on each patient's specific impairments. Research on postural responses to surface translations has shown that balance is not based on a fixed set of equilibrium reflexes but on a flexible, functional motor skill that can adapt with training and experience. More research is needed to determine the extent to which quantification of automatic postural responses has practical implications for predicting falls in patients with constraints in their postural control system.

Review↗