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Biomedical subjects

B L Finlay

Publications and source records attributed to B L Finlay.

At least 19 recordsLinked to original sources
PubMed2000

Altered development of visual subcortical projections following neonatal thalamic ablation in the hamster.

Previous research has demonstrated that precise patterns of axonal connectivity often develop during a series of stages characterized by pathfinding, target recognition, and address selection. This last stage involves the focusing of projections to a precisely defined region within the target. Because thalamic projections begin to innervate cortex before the latter stages are reached, these projections may be important in the establishment of adult-like patterns of cortical connectivity. To address this issue, we examined the mature corticopontine and corticospinal projections of visual cortex deprived of early thalamic input by visual thalamic ablation. Although ablations on the day of birth in hamsters did not disrupt the targeting of appropriate subcortical structures by visual cortical axons, they did alter the organization of projections within the basilar pons and spinal cord. The density and spread of visual corticopontine connections in lesioned animals was greatly increased relative to unlesioned animals, suggesting that thalamic afferents are required during address selection, when the topographic specificity of projections is established. To determine whether early visual thalamic ablation increases connectivity by stabilizing an exuberant developmental projection, we examined the normal development of visual corticopontine connections in hamsters ages postnatal days 1-17 (P1-P17). From the earliest ages, visual cortical axons innervate the pontine nucleus in regions specific to their adult projection zones and show progressive growth within these zones. At no time during development do projections exist that are equivalent to the projections found after thalamic ablation, suggesting that removal of thalamic input does not simply stabilize a developmental projection.

Aging↗
PubMed1999

Neural development in metatherian and eutherian mammals: variation and constraint.

A model for predicting the timing of neurogenesis in mammals (Finlay and Darlington [1995] Science 268:1578-1584) is here extended to an additional five metatherian species and to a variety of other events in neural development. The timing of both the outgrowth of axonal processes and the establishment and segregation of connections proves to be as highly predictable as neurogenesis. Expressed on a logarithmic scale, late developmental events are as predictable as early ones. The fundamental order of events is the same in eutherian and metatherian animals, but there is a curvilinear relation between the event scales of the two; for metatherians, later events are slowed relative to earlier events. Furthermore, in metatherians, the timing of developmental events is more variable than in eutherians. The slowing of late developmental events in metatherians is associated with their considerably longer time to weaning compared with eutherians.

Animals↗
PubMed1998

Patterns of vertebrate neurogenesis and the paths of vertebrate evolution.

Any substantial change in brain size requires a change in the number of neurons and their supporting elements in the brain, which in turn requires an alteration in either the rate, or the duration of neurogenesis. The schedule of neurogenesis is surprisingly stable in mammalian brains, and increases in the duration of neurogenesis have predictable outcomes: late-generated structures become disproportionately large. The olfactory bulb and associated limbic structures may deviate in some species from this general brain enlargement: in the rhesus monkey, reduction of limbic system size appears to be produced by an advance in the onset of terminal neurogenesis in limbic system structures. Not only neurogenesis but also many other features of neural maturation such as process extension and retraction, follow the same schedule with the same predictability. Although the underlying order of event onset remains the same for all of the mammals we have yet studied, changes in overall rate of neural maturation distinguish related subclasses, such as marsupial and placental mammals, and changes in duration of neurodevelopment distinguish species within subclasses. A substantial part of the regularity of event sequence in neurogenesis can be related directly to the two dimensions of the neuraxis in a recently proposed prosomeric segmentation of the forebrain [Rubenstein et al., Science, 266: 578, 1994]. Both the spatial and temporal organization of development have been highly conserved in mammalian brain evolution, showing strong constraint on the types of brain adaptations possible. The neural mechanisms for integrative behaviors may become localized to those locations that have enough plasticity in neuron number to support them.

Animals↗
PubMed1996

What do developmental mapping rules optimize?

Convergence ratios between pre- and postsynaptic cells in the visual system vary widely between cell classes, areas of the visual field, between individuals and between species. Proper stabilization of the convergence and divergence of single visual neurons is critical for visual integration generally, and for specific functions such as those of rod and cone pathways, or the center and peripheral regions of the visual field. In early development, retinal ganglion cells, target cells and all their processes are produced in excess and stabilize at certain mature values. The intent of the investigations described here is to determine what features of cell connectivity are stabilized over normal variability by these developmental processes and how such stabilization is accomplished, using the developing mammalian retinotectal system as an example. Orderly compression of the retinotopic map into a half tectum was induced by a partial tectal ablation at birth in hamsters, increasing the ratio of retinal ganglion cells to superior colliculus target cells. The convergence problem is solved in this case by undersampling the spatial array with respect to normal, preserving local spatial resolution, but potentially reducing sensitivity or introducing aliasing artifacts. Receptive field sizes of single neurons are indistinguishable from normal, and reduction of branching of presynaptic axon arbors is the mechanism of the remapping. Behaviorally, though the entire visual field is still represented in the remaining colliculus, the solution has a cost in decreased probability and increased latency to orient to visual stimuli, particularly in the peripheral visual field. The generality of this solution for retinal and other central convergence regulation problems is evaluated.

Animals↗
PubMed1995

Linked regularities in the development and evolution of mammalian brains.

Analysis of data collected on 131 species of primates, bats, and insectivores showed that the sizes of brain components, from medulla to forebrain, are highly predictable from absolute brain size by a nonlinear function. The order of neurogenesis was found to be highly conserved across a wide range of mammals and to correlate with the relative enlargement of structures as brain size increases, with disproportionately large growth occurring in late-generated structures. Because the order of neurogenesis is conserved, the most likely brain alteration resulting from selection for any behavioral ability may be a coordinated enlargement of the entire nonolfactory brain.

Adaptation, Physiological↗
PubMed1994

Regulation of retinal ganglion cell axon arbor size by target availability: mechanisms of compression and expansion of the retinotectal projection.

The ability of pre- and postsynaptic populations to achieve the proper convergence ratios during development is especially critical in topographically mapped systems such as the retinotectal system. The ratio of retinal ganglion cells to their target cells in the optic tectum can be altered experimentally either by early partial tectal ablation, which results in an orderly compression of near-normal numbers of retinal projections into a smaller tectal area, or by early monocular enucleation, which results in the expansion of a reduced number of axons in a near-normal tectal volume. Our previous studies showed that changes in cell death and synaptic density consequent to these manipulations can account for only a minor component of this compensation for the population mismatch. In this study, we examine other mechanisms of population matching in the hamster retinotectal system. We used an in vitro horseradish peroxidase labeling method to trace individual retinal ganglion cell axons in superior colliculi partially ablated on the day of birth, as well as in colliculi contralateral to a monocular enucleation. We found that individual axon arbors within the partially lesioned tectum occupy a smaller area, with fewer branches and fewer terminal boutons, but preserve a normal bouton density. In contrast, ipsilaterally projecting axon arbors in monocularly enucleated animals occupy a greater area than in the normal condition, with a much larger arbor length and greater number of boutons and branches compared with normal ipsilaterally projecting cells. Alteration of axonal arborization of retinal ganglion cells is the main factor responsible for matching the retinal and tectal cell populations within the tectum. This process conserves normal electrophysiological function over a wide range of convergence ratios and may occur through strict selectivity of tectal cells for their normal number of inputs.

Animals↗
PubMed1993

The early development of thalamocortical and corticothalamic projections.

The early development of thalamocortical and corticothalamic projections in hamsters was studied to compare the specificity and maturation of these pathways, and to identify potential sources of information for specification of cortical areas. The cells that constitute these projections are both generated prenatally in hamsters and they make reciprocal connections. Fluorescent dyes (DiI and DiA) were injected into the visual cortex or lateral geniculate nucleus in fixed brains of fetal and postnatal pups. Several issues in axonal development were examined, including timing of axon outgrowth and target invasion, projection specificity, the spatial relationship between the two pathways, and the connections of subplate cells. Thalamic projections arrive in the visual cortex 2 days before birth and begin to invade the developing cortical plate by the next day. Few processes invade inappropriate cortical regions. By postnatal day 7 their laminar position is similar to mature animals. By contrast, visual cortical axons from subplate and layer 6 cells reach posterior thalamus at 1 day after birth in small numbers. By 3 days after birth many layer 5 cell projections reach the posterior thalamus. On postnatal day 7, there is a sudden increase in the number of layer 6 projections to the thalamus. Surprisingly, these layer 6 cells are precisely topographically mapped with colabeled thalamic afferents on their first appearance. Subplate cells constitute a very small component of the corticothalamic projection at all ages. Double injections of DiI and DiA show that the corticofugal and thalamocortical pathways are physically separate during development. Corticofugal axons travel deep in the intermediate zone to the thalamic axons and are separate through much of the internal capsule. Their tangential distribution is also distinct. The early appearance of the thalamocortical pathway is consistent with an organizational role in the specification of some features of cortical cytoarchitecture. The specific initial projection of thalamocortical axons strongly suggests the recognition of particular cortical regions. The physical separation of these two pathways limits the possibility for exchange of information between these systems except at their respective targets.

Afferent Pathways↗
PubMed1993

Changes in synaptic density after developmental compression or expansion of retinal input to the superior colliculus.

The retinal projection to the superior colliculus can be made abnormally dense by inducing a "compressed" retinal projection into a subnormal tectal volume, or abnormally sparse by monocular enucleation early in development. Any or all of the features of cell number, axonal arbor, dendritic arbor, and synaptic density could potentially be adjusted to compensate for such variations in the convergence of one cell population on another. We have examined the consequences of neonatal partial tectal ablation or monocular enucleation for synaptic length, density, and relative numbers of synapse classes in the superficial gray layer of the hamster superior colliculus. Monocular enucleation resulted in a reduction of synaptic density in the superficial gray layer of the colliculus ipsilateral to the remaining eye. This decrease in density was entirely accounted for by a reduction of the number of synapses with round vesicles, large asymmetric terminal specializations, and pale mitochondria characteristic of retinocollicular terminals (RLP synapses). There was no compensatory increase in any other synaptic class. RLP synapses were larger in monocular enucleates. Partial tectal ablation had no effect on synaptic density, nor on the relative proportions of different synaptic types. Synapses of the RLP class were slightly smaller than normal. These results suggest that synaptic density is normally at a maximum that cannot be altered by increases in potential input. However, density may be reduced by decreasing the number of inputs. Terminal classes do not appear to compete with each other within the collicular volume, suggesting that postsynaptic cells controls both the classes and numbers of their potential inputs.

Animals↗
PubMed1993

Consequences of reduced cerebral blood flow in brain development. I. Gross morphology, histology, and callosal connectivity.

Reduced blood flow produced by bilateral carotid artery occlusion (BCAO) caused multiple histopathological alterations in the cerebral cortex of developing cats. BCAO was performed in the second postnatal week. At 1 and 2 months, global structural observations were made using magnetic resonance imaging (MRI). At 3 months, neuron and glial density, extent of myelination, blood vessel distribution, and the distribution of visual callosal projecting neurons (as visualized with the retrogradely transported tracer horseradish peroxidase) were assessed by light microscopy. MRI showed lateral ventricular dilatation at 1 month in five of eight subjects, with wide-ranging severity, although at 2 months only two animals still had enlarged ventricles. Histological observations at 3 months showed that neuron density in the motor cortex, but not the occipital cortex, of BACO animals was significantly lower than that in controls. BCAO animals had more dilated small vessels, again more evident in the motor cortex than in the occipital cortex. From frontal to occipital cortex, the corpus callosum was thinned and the subcortical white matter was reduced. Even with the reduction of white matter, the number of neurons in visual areas 17 and 18 contributing a callosal projection was much higher than normal. BCAO thus altered cerebral vascularization, caused neuronal death, and reduced myelinization over an area much greater than the direct area of carotid perfusion. The excess callosal projection in these animals suggests that neonatal ischemia interferes with the normal process of axon retraction during development.

Aging↗
PubMed1993

Consequences of reduced cerebral blood flow in brain development. II. Retardation of neurological outcome and phosphorus metabolism.

We investigated the temporal relationship of the emergence of biochemical abnormalities to the development of behavioral dysfunction to identify the central factors of ischemic neurological disorders in developing brains. To induce early ischemia, bilateral carotid artery occlusion (BCAO) was surgically performed on 21 cats at the second week of age. BCAO produces histopathological damage, including neuronal loss and thinning of white matter. 31P magnetic resonance spectroscopy was used to monitor brain oxidative metabolism, neuronal membrane growth, and myelination of the prefrontal cortex in the first 3 months. Neurological development was monitored by conducting 25 tests of reflex, motor, sensory, and integrated behavioral function. At 1 month, phosphodiester (PDE) levels, a component of membranes and myelin, were low in animals showing complete ligation. At 2 months, the growth of PDE was low (1/4 to 1/2 of normal) in BCAO animals, whereas normal animals demonstrated a 23% increase. Phosphocreatine (PCr) levels, indicated by PCr/ATP and PCr/inorganic phosphate ratios, were retarded at 2 months in completely ligated animals (1/4 of normal). Neurologically, the completely ligated animals showed retardation of general development. The retardation was most pronounced for integrative functions, including visual function, and became more pronounced later in development. The time course of emergence of the retardation generally coincided with emergence of abnormalities in phosphorous compounds. The simultaneous occurrence of several biochemical and functional abnormalities in development following early ischemic insult suggests a causal relationship between membrane and mitochondrial development and neurological function.

Adenosine Triphosphate↗
PubMed1992

Cell death and the creation of regional differences in neuronal numbers.

Regional variations in cell death are ubiquitous in the nervous system. In the retina, cell death in retinal ganglion cells is elevated in the retinal periphery and may be important in setting up the initial conditions that produce central retinal specializations such as an area centralis or visual streak. In central visual system structures, pronounced spatial and spatiotemporal inhomogeneities in cell death are seen both in layers and regions of the lateral geniculate nucleus and superior colliculus; similar indications of inhomogeneities are seen in those nonvisual structures that have been examined. Cell death in the cortex is highly nonuniform, by layer and by cortical area. A variety of possible functions for these regional losses are proposed, in the context of a uniform mechanism for cell death that allows it to assume multiple functions.

Animals↗
PubMed1991

Compensation for population size mismatches in the hamster retinotectal system: alterations in the organization of retinal projections.

Unilateral partial ablation of the superior colliculus in the hamster results in a compression of the retinotopic map onto the remaining tectal fragment. In a previous electrophysiological study (Pallas & Finlay, 1989a), we demonstrated that receptive-field properties of single tectal units (including receptive-field size) remain unchanged, despite the increased afferent/target convergence ratios in the compressed tecta. The present study was done to investigate the mechanism that produces increased convergence from retina to tectum at the population level while maintaining apparent stability of convergence at the single neuron level. We injected comparable quantities of horseradish peroxidase into the tecta of normal adult hamsters and adult hamsters that had received neonatal partial tectal ablations of varying magnitude. We then compared the area of retina backfilled from the injection and the number and density of labeled retinal ganglion cells within it to the size of the remaining tectal fragment. As expected from earlier anatomical (Jhaveri & Schneider, 1974) and physiological (Finlay et al., 1979a; Pallas & Finlay, 1989a) studies demonstrating compression of the retinotectal projection, we found that the area of retina labeled from a single tectal injection site increases linearly with decreasing tectal fragment size. However, for fragment sizes down to 30% of normal, total number of retinal ganglion cells projecting to the injection site remains in or above the normal range. For large lesions (less than 30% of tectum remaining), total number of labeled retinal ganglion cells declines from normal, despite the fact that a larger absolute area of retina is represented on each unit of tectum under these conditions. Comparison of retinal ganglion cell density with tectal fragment size shows an initial decline with decreasing fragment size, which becomes sharper with very large lesions (small tectal fragments). The maintenance of the normal number of retinal ganglion cells innervating each patch of tectum could be accomplished by an elimination of the tectal collaterals of some retinal ganglion cells. Our results suggest that, in addition to collateral elimination, reduction in the size of ganglion cell arbors is occurring, since the peak density of backfilled ganglion cells declines less rapidly than backfilled retinal area increases, especially for small lesions. However, arbor reduction and collateral elimination must occur in such a way that individual tectal cells represent the same amount of visual space as normal. Thus, collateral elimination and arbor reduction are two mechanisms that operate to maintain afferent/target convergence ratios (and thus receptive-field properties) over large variations in afferent availability.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1990

Developmental changes in the distribution of retinal catecholaminergic neurones in hamsters and gerbils.

Although Syrian hamsters and Mongolian gerbils are closely related, they have quite different patterns of retinal ganglion cell distribution and different patterns of retinal growth that produce their distributions. We have examined the morphology and distribution of catecholaminergic (CA) neurones in adult and developing retinae of these species in order to gain a more general understanding of the mechanisms producing cellular topographies in the retina. CA neurones were identified with an antibody to tyrosine hydroxylase (TH), the rate limiting enzyme in the production of catecholamines. In adult retinae of both hamsters and gerbils, most CA somata were located in the inner part of the inner nuclear layer (INL) and CA dendrites spread in a outer stratum of the inner plexiform layer (IPL). Their somata varied with retinal position, being largest in temporal and smallest in central retina. In hamsters, but not gerbils, a small number of CA interplexiform cells was also observed. In development, CA somata of hamster retinae were observed first in the middle and/or scleral regions of the cytoblast layer (CBL) at P (postnatal day) 8. By P12, CA somata were commonly located in the inner part of the INL and their dendrites spread into the outer region of the IPL. In developing gerbil retinae, CA somata were first observed at P6 in the middle of the CBL. Over subsequent days, they migrated into the inner part of the INL and spread their dendrites into the outer strata of the IPL. In both hamsters and gerbils, CA cells were initially concentrated in the superior temporal margin of the retina. In hamsters, this supero-temporal concentration persisted until adulthood, whereas in adult gerbils, the greatest density of CA cells was found just superior to the visual streak. These distributions were distinct from those of the ganglion cells in adult and developing retinae of each species. We discuss the role of maturational expression of TH, cell death, and retinal growth in the generation of the distinct distribution of the CA cells.

Aging↗
PubMed1989

Duration of retinogenesis: its relationship to retinal organization in two cricetine rodents.

The Mongolian gerbil (Meriones unguiculatus) has a prolonged period of development relative to other muroid rodents. We have explored the consequences of this relatively long period of maturation on retinal cell number and topography by comparing the duration and topography of neurogenesis in the gerbil retina with that of a closely related species which develops rapidly, the Syrian hamster (Mesocricetus auratus) (Sengelaub et al.: J. Comp. Neurol. 246:527-543, 1986). An analysis of thymidine-labeled retinas indicate that cells destined for the gerbil retinal ganglion cell layer are generated for at least 12 embryonic days, twice the duration in the hamster. The period of cell loss in the gerbil retinal ganglion cell layer extends for at least 14 postnatal days, more than twice as long as in the hamster. The gerbil retina is generated in a center-to-periphery gradient for both retinal ganglion cells and displaced amacrine cells, while no such gradients are evident in the hamster retina. We conclude that the longer developmental period of the gerbil is associated with 1) a longer period of neurogenesis resulting in greater retinal cell number, 2) the expression of spatial gradients in neurogenesis, and 3) a larger eye at maturity. The last two factors, in part, may be related to the development of a highly differentiated area centralis and visual streak in the retina of this rodent. Unrelated to duration of growth, early differences in retinal shape between these two species contributes to the development of retinal topography. The gerbil, but not the hamster retina, is initially asymmetric, longer in its nasotemporal than its dorsoventral dimension. The gerbil retina then grows asymmetrically, producing a spherical retina, and coincident in time, a nasotemporally extended visual streak.

Animals↗
PubMed1989

Differential elasticity of the immature retina: a contribution to the development of the area centralis?

Differential stretch of a retinal surface with an initially uniform cell density has been repeatedly implicated as one of the developmental mechanisms that produces the topographic organization of cell density in the adult retina, notably the area centralis or visual streak versus peripheral regions. It is known that intraocular pressure is required to produce the normal conformation and thinning of the retina during development. We tested the possibility that the retina has elastic properties that might permit differential stretch in conjunction with intraocular pressure. The relative deformation of the retina containing the presumptive area centralis was compared to the deformation of peripheral retina at equivalent applied fluid displacements in 7-12-day-old cats. The peripheral retina deformed significantly more, consistent with the hypothesis that differences in the local elasticities of the developing neural retina contribute to its characteristic topographic changes. Thus, a biomechanical property of the growing eye may contribute to the mechanism by which the pattern of the visual array is sampled.

Animals↗
PubMed1989

Conservation of receptive-field properties of superior colliculus cells after developmental rearrangements of retinal input.

The formation of topographic maps requires not only that afferents synapse with the appropriate targets, but that the spatial relationships between the afferents be maintained. During development, in addition to the formation of the topographic map, the connectivity patterns responsible for the receptive-field properties of the target cells are being formed. The extent of interaction between these two processes is unknown. The present study addresses this question by manipulating afferent/target ratios during development, thus altering the topography of the map, and studying the effects of this alteration on the receptive-field properties of single target cells in the adult. Partial unilateral lesions of the superior colliculus (SC) were made in neonatal hamsters. These lesions result in a compression of the retinotopic map onto the remaining collicular fragment. Single cells were recorded from the superficial gray layer of the SC in the adult in response to visual stimuli. Receptive-field properties observed in lesioned animals were compared to those in normal animals and in sham operates. Receptive-field properties were largely unaffected by the change in the topographic map. There was no difference in the receptive-field size of single tectal cells of lesioned and unlesioned animals. Stimulus velocity and stimulus size tuning functions remained the same. This raises the possibility that, rather than the expected increase in convergence of retinal ganglion cells (RGC) onto single collicular cells, single SC cells receive input from ganglion cells representing the same amount of retinal area as in unlesioned animals. The excess ganglion cells created by the partial target removal would then project elsewhere and/or reduce their arbor within the SC. Regardless of the mechanism, it is clear from our results that circuitry in the retinotectal system of the hamster can compensate for conditions of increased afferent availability and thus maintain receptive-field properties.

Animals↗
PubMed1988

Control of cell number in the developing neocortex. I. Effects of early tectal ablation.

Target availability is an important factor in the early control of neuron number in many structures in the developing vertebrate nervous system. In early neocortical development, the role of target availability in the survival of subcortically projecting neurons is not yet understood, particularly because these cells' axons are widely distributed and highly branched. In this study, we have looked for alterations in the pattern of early cell death, adult cell density and adult morphology of pyramidal cells in layer V of visual cortex consequent to removal of one of their principal targets, the ipsilateral superior colliculus. After neonatal tectal ablation, there was no difference in the incidence of pyknotic cells in the cortex overall, or in layer V during the period of normal cell death in the cortex. Neither in adulthood, nor at any point in development did the density of layer V cells or cortical cell density overall differ from normal in Nissl material. Soma size of cells in layer V overall did not differ from normal in Nissl material. In addition, the soma size of the subpopulation of cells labelled with horseradish peroxidase (HRP) from midbrain injections was unaltered. In summary, this cell population appears unresponsive in both number and morphology to deletions of a major component of its target pool. This observation has some interesting implications for reasons of constancy of cell number in layer V across cytoarchitectonic areas.

Aging↗