Biomedical subjects

M Constantine-Paton

Publications and source records attributed to M Constantine-Paton.

At least 55 records · Page 3Linked to original sources

PubMed1990

NMDA receptor agonist and antagonists alter retinal ganglion cell arbor structure in the developing frog retinotectal projection.

The development of sensory maps is thought to require an activity-dependent structural rearrangement of afferent terminal arbors within the CNS which recreates the topographic relations of sensory somata present in the periphery. In the frog retinotectal projection, activation of the NMDA receptor plays a role in this structural plasticity. Exposure of the optic tectum of tadpoles to NMDA receptor antagonists results in a rearrangement of retinal ganglion cell arbors so that their organization into a topographic projection and eye-specific stripes is disrupted (Cline et al., 1987; Cline and Constantine-Paton, 1989). Exposure of the optic tectum to the receptor agonist, NMDA, increases the eye-specific segregation of these arbors (Cline et al., 1987). We examined the projection of the supernumerary retina and the morphology of individual retinal afferent arbors of untreated, NMDA-treated, APV-treated, MK801-treated, and MK801/NMDA-treated 3-eyed tadpoles and young postmetamorphic frogs in an effort to understand how NMDA receptor activation is involved in the growth and ordering of retinal arbors. Treatments with MK801 in combination with NMDA resulted in a desegregation of eye-specific stripes, whereas treatments with MK801 or NMDA alone did not. As reported previously, APV treatment resulted in stripe desegregation without increasing the tangential area (measured from 2-dimensional drawings) of the terminal arbors. However, a detailed analysis revealed that the APV-treated tadpole arbors have 35% reduction in branch density (branch tips/area) compared to untreated 3-eyed tadpole arbors. We treated the optic tectum with a range of concentrations of NMDA prepared in the slow-release plastic Elvax. NMDA at 10(-4) M in Elvax was the optimal concentration to produce the sharpening of stripe borders. Exposure of the tectum to NMDA at 10(-6) M in Elvax produced no change in the stripe pattern, while 10(-2) M NMDA in Elvax resulted in beading of the arbors. At the optimal concentration NMDA treatment results in a 75% reduction in the number of axons crossing from a stripe to an interstripe zone. Drawings of individual HRP-labeled, NMDA-treated arbors demonstrate that they have fewer branch points and fewer branch tips. NMDA treatment reduced arbor density by approximately 50%. Arbors drawn from untreated postmetamorphic frogs have twice the branch density of arbors from untreated tadpoles. NMDA treatment in these animals reduced the branch density by 55%, comparable to the reduction seen in tadpole branch density. Our data support a specific hypothesis for NMDA receptor involvement in the activity-dependent structural refinement process within the developing retinotectal projection.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Monoclonal antibody markers for amphibian oligodendrocytes and neurons.

Few immunocytochemical probes have been developed for cold-blooded vertebrates, thus hampering analyses of cellular processes in these species. Those developed from mammalian and avian tissue often fail either to react or to show similar specificities in poikilotherms. Therefore, we have begun raising monoclonal antibodies (mabs) in mice against frog and tadpole brain tissue. The following analyses of two of these mabs suggest that these antibodies represent specific probes for frog axons and oligodendrocytes. Mab Olig recognizes all the myelinated axon tracts of the mature frog brain and spinal cord, as well as the tracts of the developing tadpole CNS once they have become myelinated. Axons cut in cross section show characteristic o-shaped staining around individual axons when processed with this antibody. Particularly easy to visualize in the tadpole are immunoreactive cell bodies and processes, seen in continuity with the myelin sheath. Occasionally, in this developing tissue, cells with highly branched processes characteristic of immature oligodendrocytes are observed. No other cells or processes within the brain or spinal cord react with this antibody. Mab Linc stains numerous filaments in all axonal projections. Occasionally, a thin rim of filamentous staining is observed in cell somata, but many regions rich in neuronal somata or dendrites are unreactive to this antibody. This in vivo staining pattern suggests that the Linc antigen is differentially distributed within neurons and exhibits a high concentration in axons. Linc immunoreactivity is robust in the processes of a subpopulation of dissociated tectal cells in culture. These Linc-positive cells are characterized as neurons on morphological criteria. Also, intense Linc immunoreactivity is present in the bundles of retinal axons that extend from retinal explants. Olig immunoreactivity, however, has not been detected in tectal cultures or retinal explants. Improved staining following Triton X-100 treatment of tissue sections suggests that neither of the mabs recognizes lipid antigens and that both are probably localized within the cell cytoplasm. Only the Linc mab reacts on Western blots of denatured brain protein. Linc consistently recognizes two Triton X-100-insoluble proteins with apparent molecular weights of 56 and 58 kD. The epitopes recognized by the Olig and Linc mabs have been surveyed in terms of their resistance to optic nerve crush and their consequent value in studies requiring such procedures. Possible homologies to known cell-type-specific molecules are discussed.

Animals↗

PubMed1989

Quantitative autoradiographic localization of NMDA, quisqualate and PCP receptors in the frog tectum.

An organizing role for the N-methyl-D-aspartate (NMDA) receptor/channel has been suggested in the development of the retinotectal projection in Rana pipiens. The regional distributions of NMDA, phencyclidine (PCP) and quisqualic acid (QA) receptors were quantified using in vitro autoradiography in the tectum of normal and surgically produced 3-eyed juvenile frogs. NMDA and QA receptor binding was highest in the pretectum. Of the tectal layers, the superficial retinotectal synaptic zone, layer 9, had the highest amount of NMDA and QA receptor binding. Moderate binding was observed in layer 5, with little binding in the cellular layer 6. No specific [3H]N-(1-[2-thienyl]cyclohexyl) piperidine ([3H]TCP) binding was observed in any of the tectal regions.

Animals↗

PubMed1989

Isolation and characterization of ganglioside 9-O-acetyl-GD3 from bovine buttermilk.

Bovine buttermilk contains a unique ganglioside, 9-O-acetyl-GD3. In order to isolate large quantities of this ganglioside, a simplified isolation scheme which consists of several ion-exchange and silica gel column chromatographic procedures was devised. The isolated 9-O-acetyl-GD3 was characterized on the basis of its thin-layer chromatographic behavior, its immunoreactivity with a specific monoclonal antibody, JONES, and by conversion to authentic GD3 by mild base treatment.

Ammonium Hydroxide↗

PubMed1989

NMDA receptor antagonists disrupt the retinotectal topographic map.

We tested the effect of two NMDA receptor antagonists, APV or MK801 (with NMDA), and the receptor agonist NMDA on the maintenance of retinal topography in frogs. Topography was assayed by measuring the dispersion of retrogradely labeled ganglion cells following a local HRP injection into the tectum. In untreated tadpoles, labeled cells covered about 5% of the retinal area. In APV- or MK801/NMDA-treated tadpoles, labeled ganglion cells covered 17% and 10% of the retinal area, respectively. Neither treatment with L-APV nor with NMDA disrupts the fidelity of the retinotectal projection. Neither APV- nor NMDA-treated ganglion cell terminals differed from untreated terminals with respect to tangential area, branch number, or branch density. These data support a role for the NDMA receptor in visual system development.

2-Amino-5-phosphonovalerate↗

PubMed1988

A developmentally regulated antigen associated with neural cell and process migration.

The distribution of an epitope recognized by the monoclonal antibody JONES has been studied immunohistochemically in the developing nervous system of the rat. In the present report, we survey selected regions of the fetal, postnatal, and adult rat nervous system to test the hypothesis that JONES binding is invariably associated with neural cell migration and axon growth in the developing rat. A series of selected developmental stages extending from embryonic day (E) 9 to adult were used in this investigation. The distribution of JONES binding was examined using indirect immunofluorescence, as well as the immunogold procedure. Particular attention was paid to regions where the positions and timing of cell and axon migrations have been well described for the rat. JONES immunoreactivity first appears at E11-12, when it is localized to the lamina terminalis, the telencephalic-diencephalic junction, the midbrain, and the rhombic lip regions of the cytologically undifferentiated neural tube. In all the regions studied, during embryonic and early postnatal life, the labeling is very intense in the ventricular zone and shows a radial array in the adjacent intermediate and marginal zones. The expression of JONES epitope correlates particularly with times of cell migration in the retina, superior colliculus, cerebellum, and telencephalon and in regions undergoing neurite extension, such as the developing optic tract, the white matter of the cerebellum, the dorsal roots, the trigeminal system, and olfactory nerve. JONES binding becomes progressively restricted in the postnatal period. In the adult brain, immunoreactivity is present only in the retina and cerebellum. In the retina, JONES labeling is present in the outer plexiform layer and optic fiber layer. The labeling in the optic fiber layer extends to the optic nerve head and stops abruptly outside the orbit. In the cerebellum, JONES shows a radially oriented pattern throughout the molecular layer and delineates the cell bodies in the Purkinje cell layer. The only non-neural regions that show JONES immunoreactivity are the adrenal medulla and the kidney glomeruli. We conclude that the antigens recognized by the JONES monoclonal antibody are associated with the migration of subsets of cells and axons within the developing rat nervous system and, consequently, may play a role in conveying selectivity to these processes.

Animals↗

PubMed1988

Developmental regulation of ganglioside antigens recognized by the JONES antibody.

The JONES monoclonal antibody has been immunocytochemically associated with regions of the developing rat brain where cell and axon migrations are occurring (Mendez-Otero et al., 1986, 1988). In the present study the antigens recognized by the JONES antibody were analyzed in a variety of brain regions and at developmental ages selected to correspond to the preceding immunocytochemical observations. In accordance with earlier results from retina, JONES binding could not be detected in SDS gels from developing brain. Binding of the antibody was, however, prominent in chloroform/methanol extracts of the same tissues, and it was completely removed from tissue sections by brief chloroform/methanol form/methanol treatment. Enzymatic analyses of chloroform/methanol extracts indicated that the JONES epitope was sensitive to neuraminidase but insensitive to proteases. Overlay assays on developed high-performance thin-layer chromatographic plates (HPTLC) indicate that in all regions the JONES epitope resides on 2 or 3 ganglioside bands, depending on the age examined. These bands migrate between ganglioside standards GD 1a and GM2 on HPTLC plates and have been designated GJ1, GJ2, and GJ3, with the higher number designating the more rapidly migrating species. Occasionally, additional bands migrating in the range of polysialogangliosides were observed. The pattern of expression of GJ species was studied in forebrain, retina, and cerebellar tissue taken from embryonic day 18 (E18), postnatal day 0 (P0), P7, P14, and adult animals. Both region-specific differences in the relative prominence of each band and stage-specific differences in the total amount of the JONES gangliosides were detected. The stage-specific differences in the amount of JONES antigens are well correlated with the developmental periods of maximal cell migration in each region. While the JONES gangliosides are most prominent in forebrain before birth, in they are most prominent during the first 2 postnatal weeks. In cerebellum, JONES antigen expression is more pronounced during the 2 periods of cell migration in this tissue. In retina, the more rapidly migrating GJ3 band was the most prominent band at all stages examined, and this same band is retained in the adult. In cerebellum and forebrain GJ3 is also the most pronounced band during development. However, in contrast to the retina, the more slowly migrating GJ1 band is retained in adult forebrain and cerebellum. A variety of non-brain tissues have also been examined for the presence of the JONES antigens.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

Relationships between segregated afferents and postsynaptic neurones in the optic tectum of three-eyed frogs.

In 3-eyed frogs, afferents from 2 eyes converge on an optic tectum that normally receives input from only 1 eye. This produces an interdigitating series of stripes, resembling the ocular dominance columns in cats and monkeys. The consequences of this induced striping on the behavior of tectal dendrites was investigated in an in vitro preparation of the tectum. Stripes were labeled by anterograde transport of a fluorescent dye (rhodamine) and postsynaptic tectal cells labeled by intracellular injections of Lucifer yellow. The same types of cells were present in both normal and striped tecta, but dendritic arbors were altered in 2 ways. In normal tecta, dendrites were most frequently biased in a rostral direction. In striped tecta, dendrites were more frequently unbiased: fewer arbors had a strong rostral bias. The second effect of stripes was on the behaviors of individual dendrites of certain cell types. Some cells, primarily those with small, highly branched arbors, had dendrites that abruptly terminated at the borders between stripes. Other cells, with larger arbors, maintained "clumps" of dendrites in both eye's stripes. While these cells had portions of their dendritic arbor in more than one stripe, each individual dendrite was restricted to a single stripe. However, the processes of many cells, especially those with extensive, medial-laterally oriented dendrites, did not respect stripe boundaries in any obvious fashion. At the border between 2 stripes, there is an abrupt discontinuity in the patterns of activity in afferent axons. The dendritic alterations seen in striped tecta suggest that correlated activity can, in some cells, modulate the spatial arrangement of dendrites, such that an individual dendrite preferentially arborizes within such areas, but not between them. These cells as a whole can accommodate uncorrelated inputs, if these are segregated onto separate dendrites. This implies that local interactions between presynaptic terminals and postsynaptic dendrites, rather than action potentials in the postsynaptic cells, may furnish important signals for the modulation of dendritic arbor shape.

Animals↗

PubMed1987

Pre- and postsynaptic correlates of interocular competition and segregation in the frog.

Segregated zones of termination between converging inputs that arise from different presynaptic populations are a common property of topographically organized zones within the vertebrate central nervous system. Increasing evidence suggests that such segregation is at least in part established on the basis of competitive interactions that depend upon the activity patterns within each afferent population. However, the cellular mechanisms of these interactions are poorly understood. We have used a preparation in which a stereotyped interdigitating pattern of retina-specific termination stripes are produced in frog tecta innervated by two retinas as a result of embryonic implantation of a third eye primordia. In these animals it has been possible to examine the relationship between the number of retinal ganglion cells in each of the retinas innervating a striped tectum, the volumetric changes in the tectum as a result of this double innervation, and the pattern of eye-specific segregation that is produced. Counts of retinal ganglion cells in the retinas of the three-eyed frogs with one completely striped tectal lobe revealed no significant differences between cell numbers in the doubly innervating retinas and the normal retinas of the same animals. The average increase in retinal ganglion cell innervation to the striped tecta of these animals was 100%. However the tecta only increased in total volume by 26%. This later increase consisted of a 25% increase in the volume of the deep lying and predominantly cellular tectal laminae and a 37% increase in the superficial retinotectal synaptic zone. In many of these same animals HRP and 3H-proline were used to differentially label the set of stripes from each retina and measurements of the extent of each projection were performed. We found that the volume of tectal neuropil occupied by a striped projection is relatively unrelated to the number of ganglion cells making up that projection. Observations of the striping pattern after HRP processing to visualize stripes in whole unsectioned tecta indicate that the periodicities and rostrocaudal orientation of stripes are robust over a wide range of relative innervation densities. When one projection is much smaller than the other, stripes appear to break down into a series of "puffs" or islands of retina-specific termination zones. Nevertheless, these puffs still have a rostrocaudal alignment and the spacing of fully formed stripes. These observations suggest that the formation of exclusive termination zones may be a threshold phenomenon: so after a certain innervation density is reached one input can take over a unit of target neuropil in an all-or-none manner.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1987

N-methyl-D-aspartate receptor antagonist desegregates eye-specific stripes.

The optic tecta of surgically produced three-eyed tadpoles were chronically exposed to the N-methyl-D-aspartate (NMDA) receptor antagonist aminophosphonovaleric acid (APV), or to NMDA itself, to assess the influence of NMDA receptor/channels on the eye-specific segregation of retinal ganglion cell (RGC) terminals that occurs whenever two retinas innervate one tectal lobe. Exposure of the tectum to the active isomer of APV produces desegregation of the RGC terminals without blocking electrical activity in the afferents or altering their terminal arbor morphology. Exposure to the inactive isomer of APV causes no perturbation of the normal stripe pattern. APV-induced desegregation is completely reversible within 2 weeks of removal of the APV. In addition, exposure of the optic tectum to NMDA results in stripes with sharper borders and fewer forks and fusions than untreated animals. These results suggest that the NMDA receptor/channel plays a role in eye-specific segregation in the three-eyed tadpole.

2-Amino-5-phosphonovalerate↗

PubMed1985

Growth cone-target interactions in the frog retinotectal pathway.

The growth cones of retinal ganglion cell axons were studied in the optic tract and tectum with horseradish peroxidase (HRP) histochemistry and electron microscopy. The ganglion cell growth cones has many morphological features similar to those described in vitro and in other in vivo systems. However, we found that some processes formed highly differentiated terminal arborizations, while retaining growth cones on many of their branches. In addition, ultrastructural examination of the tectal neuropil revealed that many ganglion cell axonal processes had characteristics of both growth cones and presynaptic endings. These findings are discussed in the context of the hypothesis of shifting connections and the evidence that retinotectal map formation involves several mechanisms, including a process that depends on the action potential activity in the optic fibers.

Animals↗

PubMed1985

The development of stimulus following in the cochlear nerve and inferior colliculus of the mouse.

The decrement of evoked response amplitudes during the presentation of repetitive clicks was examined quantitatively at the level of the eighth nerve and inferior colliculus in mice aged 13-60 days postnatal. The amplitudes of both these potentials were found to decline during the course of stimulation, this being much more severe at the onset of hearing than in adults. Furthermore the following response at the level of the cochlear nerve was adult-like by day 18, while the response at the level of the inferior colliculus continued to improve through day 24. Recordings in the inferior colliculus were consistently obtained in two different regions along the frequency axis. The regions that responded best to a lower range of frequencies (e.g. 3-9 kHz) showed a more rapid and severe decrement in the evoked response to repetitive stimulation than those regions responding best to a higher range of frequencies (e.g. 8-17 kHz). This was found to be the case for repetitive click stimuli and repetitive tone bursts. Single unit responses in the inferior colliculus were consistent with this differential decline as a function of stimulus rate seen along the frequency axis.

Age Factors↗

PubMed1985

Eye-specific segregation requires neural activity in three-eyed Rana pipiens.

The addition of a third eye primordium to the forebrain region of a Rana pipiens embryo invariably results in the development of a series of periodic, mutually exclusive eye-specific bands in tectal lobes dually innervated by the host and supernumerary fibers. A number of investigators have proposed that such source-specific segregation arises as a compromise between two mechanisms that are normally involved in retinotectal map formation: one which is dependent on cell surface affinities to align the map and produce a rough retinotopy and a second that "fine tunes" the map by stabilizing adjacent terminals from neighboring retinal ganglion cell bodies at the expense of terminals from non-neighboring cells. In this study we have tested the idea that this second "fine-tuning" mechanism is dependent on neural activity by blocking impulse activity in the optic nerves of three-eyed tadpoles. To assess the requirement for activity on the formation of bands, both normal optic nerves of 17 three-eyed tadpoles were crushed intraorbitally. Two weeks after this operation, the supernumerary retinal projection had debanded and spread to cover the entire tectum in a continuous fashion. By 4 weeks, however, the host optic fibers regenerated back to the tecta and began to form segregated stripes with the fibers from the third eye. Six to 7 weeks after the optic nerve crush the periodic pattern of eye-specific segregation characteristic of dually innervated tecta was again pronounced. When activity in all three optic nerves was eliminated with tetrodotoxin (TTX; embedded in a slow release plastic) during the last 3 weeks of this process, the fibers from the two competing eyes failed to segregate and, instead, formed two completely overlapping, continuous projections across the tectal surface. To test for the requirement of activity in the maintenance of segregation, we also subjected three-eyed tadpoles without optic nerve crush to TTX blockade for 2, 3, and 4 weeks. Animals sacrificed at 2 weeks show overlap of the projections in the rostral tectum but distinct interdigitating stripes in other regions of these lobes. After 3 weeks of blockade, segregation of the projections was less distinct in the central tectum as well. After 4 weeks of TTX blockade the terminals from both eyes spread to form continuous overlapping projections throughout the tectum. Examination of well isolated, individual retinal ganglion cell terminal arbors during this period reveals that they occupy a significantly greater area of tectum following the TTX treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1985

The sharpening of frequency tuning curves requires patterned activity during development in the mouse, Mus musculus.

Neural activity has been implicated as having both a trophic function and a role in synaptic specificity. Sensory deprivation studies in a large number of developing systems have resulted in the pathological morphology of neurons and abnormal response properties. If the relative timing of discharge among afferent terminals is a cue employed by the developing system to refine the array of synaptic connections, then altering the discharge patterns should hinder this process. In the present experiments, we investigate the role played by the temporal pattern of neural activity during the ontogeny of frequency tuning in the mouse central auditory system. Postnatal animals were exposed to acoustic stimuli, repetitive clicks, that continuously entrained a large proportion of primary afferents from the onset of hearing until an age at which tuning curves should have been adult-like. The amount of fatigue to repetitive clicks was characterized at the level of the eighth nerve and inferior colliculus in normal animals. Frequency tuning curves obtained from the inferior colliculus were used as an assay for the specificity of neural connections. Click-reared animals had significantly broader tuning curves than did normally reared mice, particularly for units with best frequencies in the 10- to 15-kHz range. Furthermore, it was found that this change could not be attributed to the selective loss of the sustained component of the response. The affected range is interpreted in terms of the frequency spectrum of the click and the fact that lower frequency regions of the inferior colliculus were found to habituate rapidly. The click-rearing environment did not appear to affect unit spontaneous activity or response latency, nor did it alter the tonotopic map in the inferior colliculus. We argue against the possibility of cochlear damage based on threshold and high frequency cutoff measurements. Mice were reared in a second acoustic environment, repetitive pulses of two added frequencies, as a control for the effects of the click stimulus. This rearing paradigm did not lead to a broadening of tuning curves. It did, however, alter the properties of bimodal tuning curves. For units with bimodal tuning curves having best frequencies in the range of the rearing frequencies, it was found that the second excitatory area had a lower than normal threshold. In addition, the frequency range separating the peaks of the two excitatory regions was statistically smaller. These results are discussed with reference to the specific frequencies used in the rearing paradigm.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

PubMed1984

Retinal ganglion cell terminals change their projection sites during larval development of Rana pipiens.

Interconnecting neuronal populations in the vertebrate CNS are typically not well matched in their overall topographic patterns of histogenesis and differentiation during development. One striking example of this mismatch is the retinotectal system of the frog, where the retina grows in concentric annuli, while the optic tectum, a major retinal target, adds new neurons at only the caudo-medial border. The retinal ganglion cell (RGC) terminals nevertheless form an organized map in the tectum during the period when the two structures are undergoing such disparate modes of growth. This led Gaze et al. (Gaze, R. M., M. J. Keating, and S. H. Chung (1974) Proc. R. Soc. Lond. (Biol.) 185: 301-330) to propose that the terminals must shift caudally during development. In the present study, we have directly tested the hypothesis of "shifting connections" by selectively labeling an identified population of RGC terminals, those at the optic nerve head (ONH), and determining their tectal projection site relative to a particular group of [3H]thymidine-labeled tectal neurons. With this double-label technique, we have found that RGC terminals from cells at the ONH move from a position rostral to the [3H]thymidine-labeled tectal cells to a position caudal to these same cells during the latter half of larval development. This represents a movement of approximately 1.4 mm across the tectal surface between stages T&K XII and T&K XXV. In addition, we have used electron microscopy and electrophysiology to demonstrate that the RGC terminals make functional synaptic connections during this period. This indicates that RGC terminals continually change the tectal neurons with which they form functional synapses during the development of the retinotectal system. We propose that such moving, but highly ordered connections can best be explained by a two stage mechanism for map formation, in which graded selective adhesions between cells in appropriate regions of retina and tectum provide the overall gross retinotopy of the projection, while competitive interactions between RGC terminals are responsible for the refinement of the precision in this system.

Animals↗

PubMed1983

Hyperplasia in the spinal sensory system of the frog. I. Plasticity in the most caudal dorsal root ganglion.

Increases in the amount of periphery available for innervation have been achieved by the unilateral removal of hindlimb dorsal root ganglion (DRGs) in Rana pipiens, a procedure which generally results in a compensatory cell number increase (hyperplasia) in the DRGs which remain. We have found that the hyperplastic response is extremely variable, and we have investigated various factors which might control its production. Our findings indicate, however, that the pattern of DRGs removed, the animal's age at the time of removal, and the survival period are not strictly related to the production of hyperplasia in hindlimb DRGs. Special emphasis has been placed on DRG 10, the caudalmost DRG which normally innervates the cloaca and sends a small projection to the hindlimb. This DRG displayed dramatic cell number increases of up to 564%. In addition, several unique features of the hyperplastic response have been observed in DRG 10. This DRG showed increases in cell number on both the operated and the unoperated sides. It showed hyperplasias in animals subjected to ganglionectomy past metamorphosis as well as during larval development. Finally the production of DRG 10 hyperplasias exclusively occurred in male pre- and postmetamorphic animals. To account for these distinctive features of DRG 10 hyperplasia, baseline studies of the normal course of proliferation and cell death in DRG 10 were undertaken. They reveal no fundamental developmental differences between DRG 10 and other hindlimb DRGs. Other mechanisms responsible for these unusual features of developmental plasticity in DRG 10 are discussed.

Animals↗

PubMed1983

Hyperplasia in the spinal sensory system of the frog. II. Central and peripheral connectivity patterns.

Central and peripheral connectivity patterns of hyperplastic dorsal root ganglia (DRGs) in Rana pipiens are examined in order to determine the relative roles of peripheral and central contacts in the production of DRG hyperplasias. The hyperplasias are produced in the intact hindlimb DRGs after the removal in tadpoles and young postmetamorphic frogs of neighboring DRGs (Davis and Constantine-Paton, '83). The peripheral target zones of the hyperplastic DRGs, determined by physiological recordings of sensory receptive fields, are found to undergo a significant degree of expansion relative to controls. Peripheral expansion is most pronounced in caudalmost DRG 10, and this effect occurs in experimental animals operated during larval and postmetamorphic stages. Further, anatomical labelling of peripheral sensory fibers coursing to the hindlimb reveals that the hyperplastic DRG 10 actually contains additional fibers projecting to the denervated regions. The central projection of the hyperplastic DRG 10 does not show corresponding increases in longitudinal arborization after the application of horseradish peroxidase to the appropriate dorsal roots. These observations are made on some of the same experimental animals in which peripheral fields are shown to have vastly expanded. We conclude that the peripheral processes of the hyperplastic DRGs are less rigidly specified than the central terminations, and that it is the periphery which plays the primary role in controlling the cell numbers increases. A second aim of this investigation is to identify whether sexually dimorphic connectivity patterns in normal frogs explain the production of DRG 10 hyperplasias exclusively in male experimental animals (Davis and Constantine-Paton, '83). We apply the same techniques used in our connectivity studies of hyperplastic DRGs to the investigation of connectivity patterns of DRG 10s in normal males and females. No sex-dependent differences in peripheral and central connectivity are found. Thus, since normal male and female frogs possess an equivalent amount of target space for DRG 10, the unique production of hyperplasias in male experimental animals cannot be explained solely on the basis of connectivity. We speculate on what other factors may be involved.

Animals↗

PubMed1983

Altered activity patterns during development reduce neural tuning.

Neonatal mice were reared in an acoustic environment that repetitively entrained activity in a large proportion of primary auditory afferents during the period when the frequency tuning of auditory neurons normally develops. The tuning curves obtained from these mice were significantly broader than those of normally reared mice of the same age. This suggests that the normal frequency tuning of neurons was prevented or delayed by synchronizing the pattern of activity imposed on the auditory pathway.

Acoustic Stimulation↗