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A L Pearlman

Publications and source records attributed to A L Pearlman.

At least 19 recordsLinked to original sources
PubMed1992

EMA: a developmentally regulated cell-surface glycoprotein of CNS neurons that is concentrated at the leading edge of growth cones.

To identify cell-surface molecules that mediate interactions between neurons and their environment during neural development, we used monoclonal antibody techniques to define a developmentally regulated antigen in the central nervous system of the mouse. The antibody we produced (2A1) immunolabels cells throughout the central nervous system; we analyzed its distribution in the developing cerebral cortex, where it is expressed on cells very soon after they complete mitosis and leave the periventricular proliferative zone. Expression continues into adult life. The antibody also labels the epithelium of the choroid plexus and the renal proximal tubules, but does not label neurons of the peripheral nervous system in the dorsal root ganglia. In dissociated cell culture of embryonic cerebral cortex, 2A1 labels the surface of neurons but not glia. Immunolabeling of neurons in tissue culture is particularly prominent on the edge of growth cones, including filopodia and the leading edge of lamellipodia, when observed with either immunofluorescence or freeze-etch immunoelectron microscopy. Immunopurification with 2A1 of a CHAPS-extracted membrane preparation from brains of neonatal mice produces a broad (32-36 kD) electrophoretic band and a less prominent 70 kD band that are sensitive to N-glycosidase but not endoglycosidase H. Thus the 2A1 antibody recognizes a developmentally regulated, neuronal cell surface glycoprotein (or glycoproteins) with complex N-linked oligosaccharide side chains. We have termed the glycoprotein antigen EMA because of its prominence on the edge membrane of growth cones. EMA is similar to the M6 antigen (Lagenaur et al: J. Neurobiol. 23:71-88, 1992) in apparent molecular weight, distribution in tissue sections, and immunoreactivity on Western blots, suggesting that the two antigens are similar or identical. Expression of EMA is a very early manifestation of neuronal differentiation; its distribution on growth cones suggests a role in mediating the interactions between growth cones and the external cues that guide them.

Animals↗
PubMed1992

Extension of filopodia by motor-dependent actin assembly.

A variety of mechanisms have been proposed to explain the forward extension of cytoplasm in advancing cells and axonal growth cones, including actin polymerization and osmotic swelling. Based on our observations of the filopodia of cultured neuronal growth cones, we propose a mechanism involving motor-induced extension and retraction. We observed that filopodia (actin-based protrusions 0.2-0.5 mu in diameter) extend and retract from growth cone lamellae at the same rate. Further, force is generated at the tips of filopodia which is sufficient to produce compressive buckling of the proximal portion of the filopodium. From our analysis of these movements we suggest that a motor protein powers both the extension and retraction of filopodia.

Actins↗
PubMed1991

Changes in the distribution of extracellular matrix components accompany early morphogenetic events of mammalian cortical development.

As a step in defining the molecular environment for development of the mammalian cerebral cortex, we have used immunohistochemistry to analyze the distribution and remodeling of three major extracellular matrix (ECM) components, fibronectin, chondroitin sulfate proteoglycan (CSPG), and tenascin, during embryonic and early postnatal stages in the mouse. Fibronectin and CSPG are distributed throughout the proliferative zone that initially comprises the thin wall of the telencephalic vesicle, but their distribution changes as newly generated cells form the preplate just beneath the pia. Immunolabeling for CSPG becomes most prominent in the preplate, and fibronectin becomes restricted to that layer. Just after this change occurs, processes of preplate neurons, visualized with antibodies to neurofilaments, become evident within the matrix-rich preplate zone. The association of fibronectin and CSPG with preplate cells persists as cortical plate neurons divide the preplate; both ECM components are now most prominent in the marginal zone and subplate, the layers above and below the cortical plate that are preplate derived. Within the preplate and its derivatives, immunolabeling of fibronectin is punctate and closely associated with radial glial processes, while labeling of CSPG is more intense and diffuse. Labeling of fibronectin and CSPG declines rapidly as the cortical plate begins to differentiate into cortex; labeling for tenascin first appears at this stage in the most mature layers, the marginal zone and subplate, then gradually becomes widespread throughout all of cortex and subcortical white matter. In early postnatal life, tenascin is eliminated from the hollows of the vibrissal barrels in the somatosensory region; it then declines rapidly throughout cortex. The association of both fibronectin and CSPG with preplate cells and the distribution of fibronectin along radial glia during early cortical development suggest that one or both of these transient cell types might produce specific ECM components or induce their local deposition. The spatial and temporal distribution of fibronectin and CSPG suggests a role in defining a destination for migrating neurons that form the cortical plate and in delineating the pathway for early axonal extension. In contrast, the relatively late appearance of tenascin correlates best with the formation of astrocytes and their processes rather than with the establishment of cortical layers or major axonal pathways. These events are well underway before labeling of tenascin is evident.

Animals↗
PubMed1990

Concentration of membrane antigens by forward transport and trapping in neuronal growth cones.

Formation of the nervous system requires that neuronal growth cones follow specific paths and then stop at recognition signals, sensed at the growth cone's leading edge. We used antibody-coated gold particles viewed by video-enhanced differential interference contrast microscopy to observe the distribution and movement of two cell surface molecules, N-CAM and the 2A1 antigen, on growth cones of cultured cortical neurons. Gold particles are occasionally transported forward at 1-2 microns/s to the leading edge where they are trapped but continue to move. Concentration at the edge persists after cytochalasin D treatment or ATP depletion, but active movements to and along edges cease. We also observed a novel outward movement of small cytoplasmic aggregates at 1.8 microns/s in filopodia. We suggest that active forward transport and trapping involve reversible attachment of antigens to and transport along cytoskeletal elements localized to edges of growth cones.

Actins↗
PubMed1990

Cortical radial glia: identification in tissue culture and evidence for their transformation to astrocytes.

Radial glia are transiently present in the developing cerebral cortex, where they are thought to guide the migration of neurons from the proliferative zone to the forming cortical plate. To provide a framework for experimental studies of radial glia, we have defined morphological and immunocytochemical criteria to identify them in primary cultures of cortical cells obtained at embryonic day 13 in the mouse. Cortical radial glia in culture for 1-2 d resemble radial glia in vivo: they have a long, thin, unbranched process extending from one or both ends of the elongated cell body and are labeled with the monoclonal antibody RC1 but not with antibodies to glial fibrillary acidic protein (abGFAP). We tested the specificity of RC1 by double-labeling with a panel of cell-type specific antibodies, and found that it labels radial glia, astrocytes, and fibroblast-like cells, but not neurons. Fibroblasts are easily distinguished from glia by morphology and by labeling with antibodies to fibronectin. To test the hypothesis that radial glia become astrocytes when their developmental role is complete, we examined their morphological and immunocytochemical development in culture. After 3-4 d in vitro radial glia develop several branched processes; in this transitional stage they are labeled by both RC1 and abGFAP. Many radial glia lose RC1 immunoreactivity as they become increasingly branched and immunoreactive to abGFAP. In areas of the cultures that have few neurons and in cultures depleted of neurons by washing, flat, nonprocess-bearing glia predominate. These cells do not lose immunoreactivity to RC1 during the 9-d period of observation even though they acquire GFAP.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1988

Cell lineage in the cerebral cortex of the mouse studied in vivo and in vitro with a recombinant retrovirus.

To analyze cell lineage in the murine cerebral cortex, we infected progenitor cells with a recombinant retrovirus, then used the retroviral gene product to identify the descendants of infected cells. Cortices were infected on E12-E14 either in vivo or following dissociation and culture. In both cases, nearly all clones contained either neurons or glia, but not both. Thus, neuronal and glial lineages appear to diverge early in cortical development. To analyze the distribution of clonally related cells in vivo, clonal boundaries were reconstructed from serial sections. Perinatally (E18-PN0), clonally related cells were radially arrayed as they migrated to the cortical plate. Thus, clonal cohorts traverse a similar radial path. Following migration (PN7-PN23), neuronal clones generally remained radially arrayed, while glial clones were variable in orientation, suggesting that these two cell types accumulate in different ways. Neuronal clones sometimes spanned the full thickness of the cortex. Thus, a single progenitor can contribute neurons to several laminae.

Animals↗
PubMed1987

Fibronectin-like immunoreactivity in the developing cerebral cortex.

In the developing cerebral cortex of the mouse, binding of antibodies directed against the extracellular matrix glycoprotein fibronectin occurs with a distinct temporal and spatial pattern. On the 10th embryonic day (E10), when the wall of the telencephalic vesicle is made up of only the proliferating cells of the ventricular zone, antifibronectin (aFN) binding is restricted to the blood vessels and pia-arachnoid. Fibronectin-like immunoreactivity first appears in the neuropil as small points of immunofluorescence among the earliest postmitotic neurons that form the preplate (E11-12). A short time later (E12-13), aFN immunoreactivity becomes more diffuse but continues to be restricted to the preplate. As newly arriving neurons form the cortical plate within the preplate (E13-14), aFN binding is present in the marginal zone above the cortical plate and in the subplate below it. Both the marginal zone and the subplate contain early afferents and the cells that were previously part of the preplate. Binding of aFN is transient; by E18-19 it has diminished to the point where it is no longer detectable except in the blood vessels and pia-arachnoid. The transient appearance of fibronectin-like immunostaining in the zones that contain early cortical afferents suggests that fibronectin plays a role in forming the migratory pathway for the growth cones of these axons. In this role it may be acting in concert with other extracellular matrix components such as hyaluronectin, glycosaminoglycans, and laminin, which have been shown to have similar spatial distributions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Toward a unified monitoring system during anesthesia.

A conceptual framework is proposed for the selection of monitored parameters during anesthesia, and a new device for monitoring the parameters in a unified manner is briefly presented. A 'basic set' of 6 parameters is proposed to cover the needs of most routine anesthesia: Blood Pressure, ECG/Heart Rate, Temperature, FiO2, FetCO2, and, Cortical Activity (by EEG spectral analysis). Additional parameters are added in accordance with specified factors such as patient status and complexity of the surgical procedure. An initial version of a new monitor, 'Cerebro Trac', designed for neurosurgery and cardiovascular surgery, is briefly presented, along with planned future capabilities and directions for its use.

Anesthesia↗
PubMed1983

Receptive-field properties of transcallosal visual cortical neurons in the normal and reeler mouse.

The receptive-field properties of neurons in the striate visual cortex of normal and reeler mutant mice were studied with single-unit recording methods in order to determine whether the connections underlying these properties are altered by the developmental abnormality in neuronal position that characterizes reeler neocortex. Neurons with a projection through the corpus callosum were selected for study because they form a physiologically identifiable class of visual cortical neurons with a characteristic distribution of receptive-field properties that can be compared for normal and reeler cortex. Transcallosal cortical neurons in area 17 near its border with area 18a were identified by antidromic stimulation delivered through bipolar electrodes in the contralateral cortex. A computer controlled the visual stimuli, data acquisition, and analysis. Transcallosal neurons were principally found in layers II-III and V in the normal cortex and in a broand band deep in the reeler cortex. These populations had similar distributions of antidromic latencies, indicating that the neurons sampled from normal and reeler cortex were taken from populations with similar axonal diameters and soma sizes. The receptive-field properties of 46 units in 22 normal mice and 28 units in 11 reeler mice were characterized. Transcallosal neurons in both normal and reeler cortex were usually binocularly responsive and dominated by input from the contralateral eye. They exhibited either nonoriented (31 and 48%, respectively) or oriented (69 and 52%) receptive fields. Tuning 10 stimulus velocity was broad, with peak velocity sensitivities ranging from 1 to 1,000 degrees/s. Directional selectivity was present in 41% of normal units ad 32% of reeler units. There was no significant difference between normal and reeler cortex in the distribution of these properties. Transcallosal neurons were also examined for the presence of an inhibitory surround by comparing their responses to moving or stationary stimuli of varying sizes. Of the tested neurons, most (11/17 in normal cortex, 6/9 in reeler) showed evidence of a decrease in response to large moving stimuli. A large proportion (16/20) of normal neurons tested with stationary flashing stimuli had some degree of surround inhibition whereas significantly fewer (5/17) neurons in reeler cortex had this property. Thus, transcallosal neurons in reeler cortex less frequently had an inhibitory surround demonstrable with stationary flashing stimuli, but this difference between normal and reeler was not apparent with a moving stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

Afferent and efferent connections of the striate and extrastriate visual cortex of the normal and reeler mouse.

In order to analyze the role of lamination in establishing the precisely ordered connectional pattern of the neocortex, we compared the afferent and efferent connections of the visual cortical areas in normal mice with those of the mutant mouse reeler (rl). The reeler mutation causes disruption of the laminar organization of the neocortex; all classes of neurons are present but are abnormally located. The corticocortical and thalamocortical connection os visual cortical areas 17, 18a, and 18b were determined in normal and reeler mice with injections of horseradish peroxidase (HRP) or HRP conjugated with wheat germ agglutinin (HRP-WGA). The diffusion of HRP-WGA is highly restricted due to the surface binding properties of the lectin; it was particularly effective in demonstrating retinotopically ordered connections. We found that the patterns of connections made the reeler mutant are indistinguishable from normal. Cortical loci in area 17 are reciprocally connected to homotopic locations in areas 18a and 18b. Area 17 is also reciprocally connected with dorsal lateral geniculate nucleus of the thalamus and projects to the superior colliculus. Areas 18a and 18b are reciprocally connected with each other and with the lateral posterior and lateral nuclei of the thalamus, respectively. In addition, we found evidence of reciprocal connections between the lateral posterior nucleus and area 17, and between the lateral nucleus and areas 17 and 18a. The results indicate the neurons in visual cortical areas of the reeler mutant mouse are capable of forming retinotopically organized corticocortical and thalamocortical connections in a pattern similar to that found in normal animals. Thus the genetic anomaly producing incorrect neuronal positioning during development of the reeler cortex does not seriously impede the pathway and target recognition mechanisms responsible for formation of functionally appropriate cortical connections.

Animals↗
PubMed1980

Retinotopic organization of striate and extrastriate visual cortex in the mouse.

Detailed retinotopic maps of primary visual cortex (area 17) and the extrastriate visual regions surrounding it (areas 18a and 18b) have been constructed for the C57BL/6J mouse using standard electrophysiological mapping techniques. Primary visual cortex (area 17), as defined cytoarchitectonically, contains one complete representation of the contralateral visual field, termed V1, in which azimuth and elevation lines are approximately orthogonal. The upper visual field is represented caudally and the nasal field laterally. Binocular cells are encountered in the cortical representation of the nasal 30--40 degrees of the visual field, and there is an expanded representation of the nasal field. Extrastriate visual cortex of the mouse, like that of other mammals, contains multiple representations of the visual field. The cytoarchitectonic region of cortex lateral and rostral to area 17, termed area 18a, contains at least two such representations. The more medial of these, which by convention we have called V2, is a narrow strip surrounding V1 on its lateral and rostral aspects; the vertical meridian lies along a portion of its common border with V1. The visual field representation in V2 is not a mirror image of that in V1; the representation of the horizontal meridian forms the lateral border of V2, and the visual field representation is split so that adjacent points on either side of the horizontal meridian are represented in nonadjacent parts of V2. The other visual field representation within area 18a, which we have termed V3, is a small but apparently complete representation that lies lateral to V2. The visual field representations medial to area 17 correspond to cytoarchitectonic area 18b. Area 18b contains two representations of the temporal visual field that we have labeled Vm-r and Vm-c, and contains little or no representation of the most nasal aspect of the field.

Animals↗
PubMed1980

Laminar distribution of receptive field properties in the primary visual cortex of the mouse.

We studied the receptive field properties of single neurons in the primary visual cortex (area 17) of the mouse and the distribution of receptive field types among the cortical laminae. Three basic receptive field types were found: 1) Cells with oriented receptive fields, many of which could be classified as simple or complex, were found in all layers of the cortex, but occurred with greater frequency in layers II and III and less commonly in Layer IV. 2) Cells with non-oriented receptive fields had ON, OFF, or ON-OFF centers; they were found in all layers but were predominant in layer IV. Two subclasses of non-oriented receptive fields were characterized based on their responses to stationary and moving stimuli. One group of cells with non-oriented receptive fields responded vigorously with sustained firing to stationary flashing stimuli, and also responded well to moving stimuli over a wide range of stimulus velocities. A second group of non-oriented cells, termed motion-selective, responded poorly or not at all to stationary stimuli and responded optimally to moving stimuli over a restricted range of velocities. 3) A distinct group of neurons, termed large field, non-oriented (LFNO) cells, were found almost exclusively in layer V. LFNO cells had receptive fields that were larger than those of the other two major classes at all visual-field locations; they also had higher rates of spontaneous activity and responded to higher stimulus velocities than the other classes. In these respects, LFNO cells resembled the layer V cells of area 17 in the cat and the layer V and VI cells of area 17 in the monkey that project to the superior colliculus. We injected horseradish peroxidase into the superior colliculus, and determined that corticotectal cells in the mouse were also located in layer V, the layer where we recorded LFNO cells. Additional evidence that some LFNO cells project to the superior colliculus was provided by preliminary experiments in which we stimulated the superior colliculus and antidromically activated cortical cells with LFNO receptive fields. Neurons with LFNO receptive fields thus constitute a class that is functionally distinct, with cell bodies that are located in a single layer (V) of area 17 in the mouse.

Animals↗
PubMed1979

Cerebral color blindness: an acquired defect in hue discrimination.

In contrast to the traditional view that striate visual cortex (area 17) is surrounded by two homogeneous cortical areas (areas 18 and 19), recent studies have shown that mammalian extrastriate visual cortex contains several anatomically and functionally distinct subregions. One such region, the V-4 complex of the rhesus monkey, is highly specialized for the analysis of color information, suggesting that a lesion in a homologous region might produce a defect in color vision while sparing other visual functions. We have studied a patient whose clinical syndrome supports this suggestion: a 44-year-old man with normal color vision suffered two cerebral infarctions that produced first a right and then a left superior homonymous quadrantanopia and also caused prosopagnosia, topographical disorientation, and severely impaired color vision. Computed tomography demonstrated extensive lesions in both inferior occipital lobes in the territories of the lateral branches of the posterior cerebral arteries, involving the lingual and medial occipitotemporal gyri bilaterally; these gyri contain the inferior portion of striate cortex and segments of extrastriate visual cortex. The patient had no difficulty in giving the correct color names associated with common objects presented either verbally or in outline drawings. Standardized testing with the Farnsworth-Munsell 100-hue test, the Nagel anomaloscope, and a method that tests for just-noticeable differences between monochromatic stimuli all showed that the patient's ability to distinguish one color from another was markedly imparied but not totally absent. In contrast, visual acuity, reading, visually guided eye movements, and stereopsis were normal. Cells in the V-4 complex of monkey extrastriate cortex are highly specialized for distinguishing one color from another; the hue discrimination deficit that was demonstrated in this patient with cerebral color blindness indicates that a region or regions with similar function has been damaged.

Adult↗
PubMed1976

Functional role of efferents to the avian retina. I. Analysis of retinal ganglion cell receptive fields.

Receptive fields of retinal ganglion cells were analyzed during extracellular microelectrode recordings in the optic tract of the lightly anesthetized pigeon. Four major types of receptive field can be distinguished among the 359 fibers studied. Twenty-five percent of the receptive fields are relatively simple, responding at on and at off to stationary spots of light in the central region. All of the receptive fields have inhibitory surrounds of varying strength that do not produce a response when illuminated alone, but antagonize responses from the central region. Motion sensitive units comprise 15% of the recorded population; they are similar to the on-off center type except that responses to stationary stimuli are absent or very weak while responses to moving stimuli are virorous. Directionally selective units also have the basic features of on-off, inhibitory surround cells, but respond to moving stimuli well from the preferred direction and not at all from the null direction. Directional cells have a broad range of null directions; in about one-third of the units the range becomes broader when the stimulus involves both center and surround of the receptive field, thus enhancing directional selectivity. Directionally selective units are common, comprising 38% of the units studied. Cells unresponsive to stimuli moving from anterior in the visual field are much more common than other types, while cells unresponsive to stimuli from posterior in the field are rare. A few units (11%) respond only at on or at off to stationary stimuli in their receptive field centers; they also have antagonistic but unresponsive receptive field surrounds. The area of the visual field sampled is uniform in regard to the relative numbers of the four major receptive field types.

Animals↗