Biomedical subjects

L Galli-Resta

Publications and source records attributed to L Galli-Resta.

15 recordsLinked to original sources

PubMed2000

The dynamics of neuronal death: a time-lapse study in the retina.

Using time-lapse video microscopy, we have followed the process of neuronal death in an intact region of the mammalian nervous system. We show here the fast dynamics of nuclear fragmentation, which is over in <1 hr for neurons undergoing apoptosis in the living rat retina. Nuclear fragmentation is accompanied by a progressive raise of intracellular calcium and followed by erratic movement of the apoptotic cells, documenting their loss of adhesion.

Amidines↗

PubMed2000

The effects of natural cell loss on the regularity of the retinal cholinergic arrays.

The retina provides a paradigmatic example of the modularity of neuronal circuitry. Different cells are stacked in layers, and neurons of the same type are commonly regularly spaced within their layer. Although the orderly arrays formed by homotypic neurons provide the basis for parallel processing, the mechanisms responsible for regular cell spacing are just beginning to be elucidated. All the developing retinal arrays for which early markers have been identified are regular before being complete. This indicates that the positional constraints controlling mosaic formation are active at times when cell genesis, migration, and death also occur in the retina. To begin investigating how these different processes are coordinated, we have focused here on the effects of cell death on the spatial organization of the two rat cholinergic mosaics, the only arrays for which the development of spatial ordering has been described quantitatively to date. We have chosen an age interval when new cell genesis is over and death predominantly or nearly exclusively controls cell number in one of these array. We found that the regularity of this array is not improved by the loss of cells occurring in this age period. Rather, death appears to be largely independent of cell position.

Animals↗

PubMed2000

The spatial organization of cholinergic mosaics in the adult mouse retina.

We analysed the spatial organization of the cholinergic amacrine cell mosaics in the mouse retina, as part of a general study of the major mouse retinal arrays, aiming at providing intrinsic cellular reference grids to monitor anomalies in retinal growth and/or functional organization in mouse models of retinal degeneration. The spatial organization of the cells was analysed by means of the nearest neighbour distance analysis, as well as by the analysis of Voronoi and Delaunay tesselations. We found non random cell spacing in both cholinergic arrays, although the mosaic in the ganglion cell layer tiles the retina scarcely better than a random distribution. Autocorrelation analysis revealed no detectable pattern in cell positioning, but there was a tendency towards a minimal spacing between array elements. Finally, we found no correlation in the spatial organization of the two arrays.

Acetylcholine↗

PubMed2000

Retinal ganglion cells with NADPH-diaphorase activity in the chick form a regular mosaic with a strong dorsoventral asymmetry that can be modelled by a minimal spacing rule.

We have identified a class of retinal ganglion cells in the chick retina that can be labelled by NADPH-diaphorase histochemistry. These cells have a remarkable topographic distribution, being restricted to the dorsal hemiretina, and form a highly regular mosaic, as revealed by the analysis of nearest neighbour distribution and Delaunay triangulation. Autocorrelation analysis of the mosaic of NADPH-diaphorase-positive retinal ganglion cells shows that the mosaic spatial organization could be generated with the single constraint that two elements cannot be closer than a given minimal distance (d(min)), which we confirmed by computer simulations. In contrast with what has been observed in other mosaics, here d(min) varies with cell density. However, the observed variation of the exclusion area is consistent with an original assembly of the mosaic with a constant d(min) (as is the case in other mosaics), followed by differential expansion of the retina during development.

Animals↗

PubMed2000

Local, possibly contact-mediated signalling restricted to homotypic neurons controls the regular spacing of cells within the cholinergic arrays in the developing rodent retina.

In the vertebrate retina neurons of the same type commonly form non-random arrays, assembled by unknown positional mechanisms during development. Computational models in which no two cells are closer than a minimal distance, simulate many retinal arrays. These findings have important biological implications, since they suggest that cells are determined as neurons of specific types before entering their arrays, and that local, possibly contact-mediated interactions acting exclusively among the elements of an array account for its assembly. This is here verified by combining experimental manipulations in normal and transgenic models with computational analysis for the cholinergic mosaics, the only arrays so far for which the development of spatial ordering is known quantitatively. When generalised, these findings suggest a plan for vertebrate retinal patterning, where homotypic interactions organise retinal arrays first, then local interactions between synaptic partners suffice to establish the topographical connections that support retinal processing.

Acetylcholine↗

PubMed1999

Modelling the mosaic organization of rod and cone photoreceptors with a minimal-spacing rule.

The mosaic of photoreceptors is regarded as a prime example of the precise control of cellular positioning in the vertebrate nervous system. This study was undertaken with the idea that understanding the intrinsic geometrical features of photoreceptor mosaics is a necessary step to unveil the biological mechanisms governing their formation. We show in the retina of the ground squirrel that the arrays of both the rods and S cones are non-random, but that nothing more than a simple minimal-spacing rule constraining receptor positioning is sufficient to account for the spatial organization of both mosaics. The size of this 'exclusion zone' is an intrinsic characteristic of each cell type, and it is simply the difference in the size of this domain that accounts for the regularity of the S cone array and the irregularity of the rod array at identical density. Consequently, regularity in receptor mosaics is produced by two independent biological events, one embodying the exclusion zone, and another specifying the local density of a given receptor type.

Animals↗

PubMed1998

Patterning the vertebrate retina: the early appearance of retinal mosaics.

The vertebrate retina is an extraordinary example of the modular design of the nervous tissue. Retinal neurons are organized in layers and, within each layer, cells of the same type commonly form orderly planar arrays - the retinal mosaics - which provide the basis for powerful parallel processing of the visual scene. Recent evidence indicates that the assembly of neuronal mosaics is an early event in retinal development, a finding with important implications for the control of genesis, fate determination, migration and death of developing retinal neurons.

Animals↗

PubMed1997

Mosaics of islet-1-expressing amacrine cells assembled by short-range cellular interactions.

The nervous system has a modular architecture with neurons of the same type commonly organized in nonrandom arrays or mosaics. Modularity is essential to parallel processing of sensory information and has provided a key element for brain evolution, but we still know very little of the way neuronal mosaics form during development. Here we have identified the immature elements of two retinal mosaics, the choline acetyltransferase (ChAT) amacrine cells, by their early expression of the homeodomain protein Islet-1, and we show that spatial ordering is an intrinsic property of the two Islet-1 mosaics, dynamically maintained while new elements are inserted into the mosaics. Migrating Islet-1 cells do not show this spatial ordering, indicating that they must move tangentially as they enter the mosaic, under the action of local mechanisms. Clonal territory analysis in X-inactivation transgenic mice confirms the lateral displacement of ChAT amacrine cells away from their clonal columns of origin, and mathematical models show how short-range cellular interactions can guide the assemblage of these mosaics via a simple biological rule.

Animals↗

PubMed1996

An intrinsic time limit between genesis and death of individual neurons in the developing retinal ganglion cell layer.

We tested the possibility that a temporal relationship exists between genesis and death of individual neurons dying during development. For this purpose, we labeled neurons born in limited time intervals and determined when they die in the ganglion cell layer (GCL) of the rat retina. We found that most neurons that die do so within a maximal interval of 5 d after their birth, irrespective of the age of genesis or of the cell type. These findings suggest the existence of a cellular clock regulating neuronal death during development. We found also that neurons migrate in no less than 3 d to the GCL, where a majority of cells that die remain a maximum of 2 d. This fast cellular turnover implies that the magnitude of neuronal death is far greater than previously believed.

Animals↗

PubMed1994

Not so humane.

Explore the source record for details and available documents.

Animal Welfare↗

PubMed1993

Afferent spontaneous electrical activity promotes the survival of target cells in the developing retinotectal system of the rat.

This study was undertaken to investigate the role of afferent spontaneous electrical activity in regulating death of target cells in the developing mammalian visual system. We show here that naturally occurring cell death in the rat superior colliculus is greatly augmented when the spontaneous firing of retinal ganglion cells is transiently blocked with TTX. An increased number of dying cells is already observed after 1 hr of afferent blockade. A 50% increase of cell death is reached after 3 hr of blockade, an effect that closely parallels increased cell death caused by eye enucleation after similar intervals of time. These results suggest that, during development, input cells exert a trophic action on target cells, which is prevented by silencing input electrical activity. A likely explanation of this effect is that the spontaneous firing of input cells causes the release by afferent fibers of a trophic agent promoting the survival of target cells.

Aging↗

PubMed1992

A quantitative model for the regulation of naturally occurring cell death in the developing vertebrate nervous system.

Throughout the animal kingdom, the formation of the nervous system involves the elimination of many cells soon after their generation. This phenomenon, known as naturally occurring cell death, has precise time schedules and is observed in the vast majority of neural structures. It causes the loss of 15-85% of the neurons generated. Manipulations of the target structure can considerably affect the amount of cell death in a nervous center, but the regulation of this process is still controversial. While in some experiments cell death leads to a linear relationship between the size of the target and that of the input, other experiments show dramatic deviations from a linear prediction. It is quite possible that cell death is regulated by different mechanisms in different cases and that the search for a single explanation would be doomed to failure. However, it is shown here that if mutual trophic interactions are assumed to occur between connected structures, a general model can be developed for the regulation of histogenetic cell death in the developing nervous system of vertebrates. The model relies on few assumptions, all derived from a number of experimental studies. Cells destined to form a neural center are generated according to a program and die around a certain age unless a trophic factor is supplied that prevents their death. Target cells exert a trophic influence on input cells and vice versa. The model quantitatively describes the time course and the amount of cell death in neural structures, thereby reconciling in a unitary framework experimental findings that until now have appeared conflicting.

Animals↗

PubMed1991

Plasticity in innervation of the rat superior colliculus by transplanted retinae as a result of eye removal at maturity.

When the superior colliculus of a rat is innervated by inputs from both eyes as well as a retina transplanted intracranially over one tectum at birth, the tectal projection from the transplant is confined mainly to the superficial surface of the superior colliculus. The transplant-derived fibers possess a simple morphology, lacking terminal arborizations. If the contralateral eye is removed one month after transplantation, these fibers can be induced to arborize into the denervated portion of the superior colliculus over the next month. This demonstration of sprouting in a mature sensory relay system raises the possibility that an enhancement of behavioral responses mediated by transplanted retina might also occur. In turn, this may provide an ideal system to study the correlation between anatomical changes in transplant axons and changes in behaviors mediated by transplant activity.

Animals↗

PubMed1990

Correlation in the discharges of neighboring rat retinal ganglion cells during prenatal life.

The spontaneous discharges of neighboring retinal ganglion cells were recorded simultaneously in anesthetized prenatal rats between embryonic days 18 and 21. We report here that in the majority of cases the firings of neighboring retinal ganglion cells are strongly correlated during prenatal life. Correlation in the discharges of neighboring cells during development has long been suggested as a way to consolidate synaptic connections with a target cell onto which they converge, a model first proposed by Hebb. Correlation in the activities of neighboring neurons in the retina could be the basis of developmental processes such as refinement of retinotopic maps in the brain and segregation of the inputs from the two eyes.

Animals↗

PubMedDate not supplied

The topography of rod and cone photoreceptors in the retina of the ground squirrel.

The distributions of rod and cone photoreceptors have been determined in the retina of the California ground squirrel, Spermophilus beecheyi. Retinas were fixed by perfusion and the rods and cones were detected with indirect immunofluorescence using opsin antibodies. Local densities were determined at 2-mm intervals across the entire retina, from which total numbers of each receptor type were estimated and isodensity distributions were constructed. The ground squirrel retina contains 7.5 million cones and 1.27 million rods. The peak density for the cones (49,550/mm2) is found in a horizontal strip of central retina 2 mm ventral to the elongated optic nerve head, falling gradually to half this value in the dorsal and ventral retinal periphery. Of the cones, there are 14 M cones for every S cone. S cone density is relatively flat across most of the retina, reaching a peak (4500/mm2) at the temporal end of the visual streak. There is one exception to this, however: S cone density climbs dramatically at the extreme dorso-nasal retinal margin (20,000/mm2), where the local ratio of S to M cones equals 1. Rod density is lowest in the visual streak, where the rods comprise less than 5% of the local photoreceptor population, increasing conspicuously in the ventral retina, where the rods achieve 30% of the local photoreceptor population (13,000/mm2). The functional importance of the change in S to M cone ratio at the dorsal circumference of the retina is compromised by the extremely limited portion of the visual field subserved by this retinal region. The significance for vision, if any, remains to be determined. By contrast, the change in rod/cone ratio between the dorsal and ventral halves of the retina indicates a conspicuous asymmetry in the ground squirrel's visual system, suggesting a specialization for maximizing visual sensitivity under dim levels of illumination in the superior visual field.

Animals↗