The early development of retinal ganglion cells with uncrossed axons in the mouse: retinal position and axonal course

Development ◽  
1990 ◽  
Vol 108 (3) ◽  
pp. 515-523 ◽  
Author(s):  
R.J. Colello ◽  
R.W. Guillery

The carbocyanine dye, DiI, has been used to study the retinal origin of the uncrossed retinofugal component of the mouse and to show the course taken by these fibres through the optic nerve and chiasm during development. Optic axons first arrive at the chiasm at embryonic day 13 (E13) but do not cross the midline until E14. After this stage, fibres taking an uncrossed course can be selectively labelled by unilateral tract implants of DiI. The earliest ipsilaterally projecting ganglion cells are located in the dorsal central retina. The first sign of the adult pattern of distribution of ganglion cells with uncrossed axons located mainly in the ventrotemporal retina is seen on embryonic day 16.5, thus showing that the adult line of decussation forms early in development. A small number of labelled cells continue to be found in nasal and dorsal retina at all later stages. At early stages (E14-15), retrogradely labelled uncrossed fibres are found in virtually all fascicles of the developing nerve, intermingling with crossed axons throughout the length of the nerve. At later stages of development (E16-17), although uncrossed fibres pass predominantly within the temporal part of the stalk, they remain intermingled with crossed axons. A significant number of uncrossed axons also lie within the nasal part of the optic stalk. The position of uncrossed fibres throughout the nerve in the later developmental stages is comparable to that seen in the adult rodent (Baker and Jeffery, 1989). The distribution of uncrossed axons thus indicates that positional cues are not sufficient to account for the choice made by axons when they reach the optic chiasm.

2020 ◽  
Author(s):  
Kwang Wook Min ◽  
Namsuk Kim ◽  
Jae Hoon Lee ◽  
Younghoon Sung ◽  
Museong Kim ◽  
...  

ABSTRACTIn animals that exhibit stereoscopic visual responses, the axons of retinal ganglion cells (RGCs) connect to brain areas bilaterally by forming a commissure called the optic chiasm (OC). Ventral anterior homeobox 1 (Vax1) contributes to formation of the OC, acting endogenously in optic pathway cells and exogenously in growing RGC axons. Here, we generated Vax1AA/AA mice expressing the Vax1AA mutant, which is selectively incapable of intercellular transfer. We found that RGC axons cannot take up Vax1AA protein from Vax1AA/AA mouse optic stalk (OS) cells, of which maturation is delayed, and fail to access the midline. Consequently, RGC axons of Vax1AA/AA mice connect exclusively to ipsilateral brain areas, resulting in the loss of stereoscopic vision and the inversed oculomotor responses. Together, our study provides physiological evidence for the necessity of intercellular transfer of Vax1 and the importance of the OC in binocular visual responses.


Development ◽  
1994 ◽  
Vol 120 (6) ◽  
pp. 1643-1649 ◽  
Author(s):  
K.H. Herzog ◽  
K. Bailey ◽  
Y.A. Barde

Using a sensitive and quantitative method, the mRNA levels of brain-derived neurotrophic factor (BDNF) were determined during the development of the chick visual system. Low copy numbers were detected, and BDNF was found to be expressed in the optic tectum already 2 days before the arrival of the first retinal ganglion cell axons, suggesting an early role of BDNF in tectal development. After the beginning of tectal innervation, BDNF mRNA levels markedly increased, and optic stalk transection at day 4 (which prevents subsequent tectal innervation) was found to reduce the contralateral tectal levels of BDNF mRNA. Comparable reductions were obtained after injection of tetrodotoxin into one eye, indicating that, already during the earliest stages of target encounter in the CNS, the degree of BDNF gene expression is influenced by activity-dependent mechanisms. BDNF mRNA was also detected in the retina itself and at levels comparable to those found in the tectum. Together with previous findings indicating that BDNF prevents the death of cultured chick retinal ganglion cells, these results support the idea that the tightly controlled expression of the BDNF gene might be important in the co-ordinated development of the visual system.


2020 ◽  
Author(s):  
Shahad Albadri ◽  
Olivier Armant ◽  
Tairi Aljand-Geschwill ◽  
Filippo Del Bene ◽  
Matthias Carl ◽  
...  

AbstractPromoting the regeneration or survival of retinal ganglion cells (RGCs) is one focus of regenerative medicine. Homeobox Barhl transcription factors might be instrumental in these processes. In mammals, only barhl2 is expressed in the retina and is required for both subtype identity acquisition of amacrine cells and for the survival of RGCs downstream of Atoh7, a transcription factor necessary for RGC genesis. The underlying mechanisms of this dual role of Barhl2 in mammals have remained elusive. Whole genome duplication in the teleost lineage generated the barhl1a and barhl2 paralogues. In the Zebrafish retina, Barhl2 functions as determinant of subsets of amacrine cells lineally related to RGCs independently of Atoh7. In contrast, barhl1a expression depends on Atoh7 but its expression dynamics and function have not been studied. Here we describe for the first time a Barhl1a:GFP reporter line in vivo showing that Barhl1a turns on exclusively in subsets of RGCs and their post-mitotic precursors. We also show transient expression of Barhl1a:GFP in diencephalic neurons extending their axonal projections as part of the post-optic commissure, at the time of optic chiasm formation. This work sets the ground for future studies on RGC subtype identity, axonal projections and genetic specification of Barhl1a-positive RGCs and commissural neurons.


2020 ◽  
Vol 6 (37) ◽  
pp. eabb6642
Author(s):  
Paul Werginz ◽  
Vineeth Raghuram ◽  
Shelley I. Fried

Recently, mouse OFF-α transient (OFF-α T) retinal ganglion cells (RGCs) were shown to display a gradient of light responses as a function of position along the dorsal-ventral axis; response differences were correlated to differences in the level of excitatory presynaptic input. Here, we show that postsynaptic differences between cells also make a strong contribution to response differences. Cells in the dorsal retina had longer axon initial segments (AISs)—the greater number of Nav1.6 channels in longer AISs directly mediates higher rates of spiking and helps avoid depolarization block that terminates spiking in ventral cells with shorter AISs. The pre- and postsynaptic specializations that shape the output of OFF-α T RGCs interact in different ways: In dorsal cells, strong inputs and the long AISs are both necessary to generate their strong, sustained spiking outputs, while in ventral cells, weak inputs or the short AISs are both sufficient to limit the spiking signal.


1990 ◽  
Vol 110 (2) ◽  
pp. 437-448 ◽  
Author(s):  
R A Nixon ◽  
I Fischer ◽  
S E Lewis

Microtubule-associated proteins (MAPs) in neurons establish functional associations with microtubules, sometimes at considerable distances from their site of synthesis. In this study we identified MAP 1A in mouse retinal ganglion cells and characterized for the first time its in vivo dynamics in relation to axonally transported tubulin. A soluble 340-kD polypeptide was strongly radiolabeled in ganglion cells after intravitreal injection of [35S]methionine or [3H]proline. This polypeptide was identified as MAP 1A on the basis of its co-migration on SDS gels with MAP 1A from brain microtubules; its co-assembly with microtubules in the presence of taxol or during cycles of assembly-disassembly; and its cross-reaction with well-characterized antibodies against MAP 1A in immunoblotting and immunoprecipitation assays. Glial cells of the optic nerve synthesized considerably less MAP 1A than neurons. The axoplasmic transport of MAP 1A differed from that of tubulin. Using two separate methods, we observed that MAP 1A advanced along optic axons at a rate of 1.0-1.2 mm/d, a rate typical of the Group IV (SCb) phase of transport, while tubulin moved 0.1-0.2 mm/d, a group V (SCa) transport rate. At least 13% of the newly synthesized MAP 1A entering optic axons was incorporated uniformly along axons into stationary axonal structures. The half-residence time of stationary MAP 1A in axons (55-60 d) was 4.6 times longer than that of MAP 1A moving in Group IV, indicating that at least 44% of the total MAP 1A in axons is stationary. These results demonstrate that cytoskeletal proteins that become functionally associated with each other in axons may be delivered to these sites at different transport rates. Stable associations between axonal constituents moving at different velocities could develop when these elements leave the transport vector and incorporate into the stationary cytoskeleton.


2016 ◽  
Author(s):  
Gerrit Hilgen ◽  
Sahar Pirmoradian ◽  
Daniela Pamplona ◽  
Pierre Kornprobst ◽  
Bruno Cessac ◽  
...  

AbstractWe have investigated the ontogeny of light-driven responses in mouse retinal ganglion cells (RGCs). Using a large-scale, high-density multielectrode array, we recorded from hundreds to thousands of RGCs simultaneously at pan-retinal level, including dorsal and ventral locations. Responses to different contrasts not only revealed a complex developmental profile for ON, OFF and ON-OFF RGC types, but also unveiled differences between dorsal and ventral RGCs. At eye-opening, dorsal RGCs of all types were more responsive to light, perhaps indicating an environmental priority to nest viewing for pre-weaning pups. The developmental profile of ON and OFF RGCs exhibited antagonistic behavior, with the strongest ON responses shortly after eye-opening, followed by an increase in the strength of OFF responses later on. Further, we found that with maturation receptive field (RF) center sizes decrease, responses to light get stronger, and centers become more circular while seeing differences in all of them between RGC types. These findings show that retinal functionality is not spatially homogeneous, likely reflecting ecological requirements that favour the early development of dorsal retina, and reflecting different roles in vision in the mature animal.


Development ◽  
1987 ◽  
Vol 101 (2) ◽  
pp. 323-337
Author(s):  
D.L. Becker ◽  
J.E. Cook

The optic tract of the goldfish splits into two brachia just before it reaches the tectum, normal optic axons being distributed systematically between the two according to their retinal origins. The orderliness of this division, like that of the retinotectal projection itself, is conventionally attributed to a system of specific axonal guidance cues. However, the brachial distribution of regenerated axons is much less orderly; and, since there is evidence that these axons have many collateral branches in the nerve and tract, the gross order that remains after regeneration could potentially arise secondarily, in parallel with refinement of the retinotectal map, by a preferential loss of collaterals from the inappropriate brachium. The brachial paths of normal axons, and axons regenerated after optic nerve cut for periods ranging from 19 days to 5 years, were therefore studied by anterograde labelling with horseradish peroxidase from discrete retinal lesions or retrograde labelling of ganglion cells from a cut brachium. From 19 to 28 days, regenerating axons showed little or no preference for their normal brachium. During this period (which includes the first week of tectal synaptogenesis) an average of 46á3% of cells retrogradely labelled from a cut medial brachium were in dorsal retina, compared with only 1á45% in normal fish. Some preference for the normal brachium was evident at 35 days and significant order had returned by 42–70 days, when the average proportion of labelled cells in dorsal retina had fallen to 25á4% though the average number in the whole retina was unchanged. Thus a brachial refinement had occurred in parallel with refinement of the retinotectal map. These results support the idea of a selective loss of axon collaterals from the inappropriate brachium, though they do not exclude the possibility of some concurrent gain in the appropriate one. We suggest that refinement may depend on a process we term ‘sibling rivalry’: competition between different collaterals of the same axon to form a critical number of stable tectal synapses, in which the most- normally-routed branches have the best chance of succeeding and surviving. Developing normal axons might also make use of collateral formation and ‘sibling rivalry’ to generate and refine the complex interwoven patterns of the normal optic tract.


1987 ◽  
Vol 57 (1) ◽  
pp. 218-244 ◽  
Author(s):  
L. R. Stanford

Intracellular recording and iontophoresis of horseradish peroxidase were used to study the morphology of physiologically characterized W-cells in the cat retina. The recording experiments were performed in an in vivo preparation to allow the responses of these retinal ganglion cells to be compared with previous functional studies of these neurons. The physiological and morphological characteristics of 16 injected and recovered retinal W-cells were compared with similar data from 14 retinal X-cells injected in the same preparations. The soma sizes of retinal W-cells were found to fall into two distinct groups. The somata of the phasic W-cells, at every eccentricity, were smaller than the somata of tonic W-cells, with no overlap between the two distributions. Soma sizes of the tonic W-cells fell into the previously described “medium-sized” range of retinal ganglion cell soma sizes and were similar to, although slightly larger than, the soma sizes of physiologically identified beta- or X-cells. The dendritic arbors of all of the cells physiologically classified as tonic W-cells were similar. Every example of this type had four to five primary dendrites that branched a short distance from the soma to form a circular or cruciate dendritic arbor. The dendritic arrays of these cells were easily distinguishable from the compact dendritic arbors of the physiologically identified X-cells. The dendritic arbors of the phasic W-cells were much more heterogeneous, ranging from sparse, wide dendritic arbors to very compact dendritic arbors with many fine branches. No significant correlation was found between the extent of the dendritic arbor and the distance from the area centralis for either the tonic W-cells or the phasic W-cells. The axons of the tonic and phasic W-cells differed from one another and from X-cells on a number of different morphological and physiological measures. The intraretinal segments of the axons of the phasic W-cells had the smallest diameters of the three groups; the axons of X-cells in the retina were relatively large, and the axons of the tonic W-cells had diameters intermediate between the phasic W-cells and the X-cells. Although considerable overlap was seen between the X-cells, tonic W-cells, and phasic W-cells in their antidromic latencies to electrical stimulation of the optic chiasm, the intraretinal and extraretinal components of the conduction velocities of the three groups were significantly different.(ABSTRACT TRUNCATED AT 400 WORDS)


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Nicolás M. Díaz ◽  
Luis P. Morera ◽  
Daniela M. Verra ◽  
María A. Contin ◽  
Mario E. Guido

The retina is a key component of the vertebrate circadian system; it is responsible for detecting and transmitting the environmental illumination conditions (day/night cycles) to the brain that synchronize the circadian clock located in the suprachiasmatic nucleus (SCN). For this, retinal ganglion cells (RGCs) project to the SCN and other nonvisual areas. In the chicken, intrinsically photosensitive RGCs (ipRGCs) expressing the photopigment melanopsin (Opn4) transmit photic information and regulate diverse nonvisual tasks. In nonmammalian vertebrates, two genes encodeOpn4: theXenopus(Opn4x) and the mammalian (Opn4m) orthologs. RGCs express bothOpn4genes but are not the only inner retinal cells expressingOpn4x: horizontal cells (HCs) also do so. Here, we further characterize primary cultures of both populations of inner retinal cells (RGCs and HCs) expressingOpn4x. The expression of this nonvisual photopigment, as well as that for different circadian markers such as the clock genesBmal1,Clock,Per2, andCry1, and the key melatonin synthesizing enzyme, arylalkylamineN-acetyltransferase (AA-NAT), appears very early in development in both cell populations. The results clearly suggest that nonvisual Opn4 photoreceptors and endogenous clocks converge all together in these inner retinal cells at early developmental stages.


1988 ◽  
Vol 102 (1) ◽  
pp. 92-101 ◽  
Author(s):  
Manuel Vidal-Sanz ◽  
María P. Villegas-Pérez ◽  
Garth M. Bray ◽  
Albert J. Aguayo

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