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Evidence for spatial regularity among retinal ganglion cells that project to the accessory optic system in a frog, a reptile, a bird, and a mammal.

The vertebrate retina contains only five major neuronal classes but these embrace a great diversity of discrete types, many of them hard to define by classical methods. Consideration of their spatial distributions (mosaics) has allowed new types, including large ganglion cells, to be resolved across a wide range of vertebrates. However, one category of large ganglion cells has seemed refractory to mosaic analysis: those that project to the accessory optic system (AOS) and serve vestibulocerebellar mechanisms of motion detection and image stabilization. Whenever AOS-projecting cells have been analyzed by nearest-neighbor methods, their distribution has appeared almost random. This is puzzling, because most aspects of visual processing require the visual scene to be sampled regularly. Here, spatial correlogram methods are applied to distributions of large ganglion cells, labeled retrogradely from the AOS in frogs, turtles, and rats, and to the AOS-projecting displaced ganglion cells of chickens. These methods reveal hidden spatial order among AOS-projecting populations, of a form that can be simulated either by superimposing a single regular mosaic on a random population or, more interestingly, by overlapping three or more regular, similar but spatially independent mosaics. The rabbit is known to have direction-selective ganglion cells (not, however, AOS projecting) that can be subdivided into functionally distinct, regular mosaics by their tracer-coupling patterns even though they are morphologically homogeneous. The present results imply that the direction-selective AOS-projecting ganglion cells of all vertebrates may, likewise, be subdivided into regular, independent mosaics.

Accessory Nerve↗

Evidence for low-voltage-activated (LVA) calcium currents in the dendrites of tiger salamander retinal ganglion cells.

We have evaluated the spatial distribution of low-voltage-activated calcium currents in ganglion cells of the tiger salamander retina. Whole-cell recordings were obtained from ganglion cells in a retinal slice preparation and from acutely dissociated ganglion cells that were identified through retrograde dye injection. In single dissociated cells, we estimated the magnitude (pA) and current density (pA/pF) of LVA currents in ganglion cells, both with and without dendritic processes. Ganglion cells that retained a portion of their dendritic arbor had larger LVA calcium currents and higher LVA current densities than those which lacked processes. When cell capacitance measurements were used to derive the surface area of the soma and dendritic processes, we concluded that a higher LVA current density was present in the dendrites; we estimate that, on average, the current density in the dendrites is approximately five times that of the soma. The presence of a significant density of LVA calcium channels in the dendrites of ganglion cells suggests that they could be involved in a number of cellular functions, including dendritic integration of synaptic currents, impulse generation, and homeostatic functions related to changes in the intradendritic calcium concentration.

Ambystoma↗

Evidence for glycine, GABAA, and GABAB receptors on rabbit OFF-alpha ganglion cells.

Inhibitory synaptic transmission via GABA and glycine receptors plays a crucial role in shaping the excitatory response of neurons in the retina. Whole-cell recordings were obtained from ganglion cells in the intact rabbit eyecup preparation to correlate GABA- and glycine-activated currents with the presence of their specific receptors on morphologically identified a ganglion cells. Alpha ganglion cells were chosen based upon their large somata when viewing the retinal surface, and responses to light and dark spots were used to identify OFF-alpha ganglion cells. Light responses were abolished by superfusion of Ringer's containing cobalt to synaptically isolate the cell by blocking all Ca(2+)-mediated transmitter release. Pressure pulses of GABA and glycine were delivered to an area that encompassed the dendritic field while receptor antagonists were applied through superfusion to characterize the direct inhibition onto the ganglion cell. Physiological results indicated that OFF-alpha cells did not have any GABAc receptor-activated currents, but did express currents mediated by ionotropic GABAA receptors and metabotropic GABAB receptors that were blocked by their specific antagonists bicuculline and CGP55845, respectively. The amplitudes of strychnine-sensitive glycine-activated currents were always larger than the currents elicited by GABA. Confocal optical sections of physiologically identified, sulforhodamine B-stained cells displayed the localization of glycine and GABAA receptor subunit labeling dispersed over the stained dendrites. Although scant labeling of GABAB receptors was found on the more distal dendrites, the majority of these receptors were congregated at the soma and on the proximal dendrites close to the soma. No GABAc receptor immunoreactivity was found anywhere on these cells. Therefore, the immunocytochemical results corroborated the physiological evidence demonstrating that OFF-alpha ganglion cells in the rabbit retina express functional GABAA, GABAB, and glycine receptors, but no GABAc receptors.

Animals↗

Cone and rod inputs to murine retinal ganglion cells: evidence of cone opsin specific channels.

To identify ultraviolet (UV) and middle- (M) wavelength-sensitive cone and rod signals in murine retinal ganglion cells, single ganglion cell responses were studied in anesthetized, light-adapted C57/BL6 mice with tungsten microelectrodes driven through the sclera and vitreous to the neural retina. One hundred fifty-four ganglion cells were examined in 43 retinas of 34 mice. The retina was stimulated with diffuse flashes and/or pulses of ultraviolet (360 nm) or green (520 nm) light in the presence and absence of a strong steady orange adapting light. Twelve ganglion cells were studied in the dark-adapted retina in order to identify the signals of rods. Three functionally different types of ganglion cells were found: (1) phasic responding cells (31%) with no spontaneous activity and large impulse amplitudes; (2) tonic responding cells (60%) with irregular, low frequency (5-10 Hz) spontaneous activity and smaller impulse amplitudes; and (3) metronome-like cells (9%) with regular, relatively high-frequency (20-40 Hz) spontaneous activity. A few cells (1%) had habituating responses. Every cell encountered was affected by diffuse stimulation. The more common two types were excited at either the ON or OFF or at both the ON and OFF phases of stimulation. Type III cells had weaker responses, sometimes only inhibited by turning off a light. In the light-adapted state, most cells received signals of the same polarity from UV- and M-cones but UV-cone inputs were usually more dominant, especially in ventral retina. A fraction of cells received signals from only UV- (18%) or only M- (3%) cones. In rare cases (2%) these cone inputs had an opposite polarity on the same cell. In the dark-adapted state, all cells were at least four or five logarithmic units more sensitive and more to green than ultraviolet light. The results indicate that co-expression of both UV-and M-cone opsins cannot be ubiquitous in murine retina. Some cones, especially UV cones, exist without the presence of any functional M-cone opsin. This must be the case to explain the presence of ganglion cells that receive inputs only from UV-cones and others that receive inputs of opposite polarity from UV- and M-cones. The results support the hypothesis that murine retina has the physiological capacity to relay signals to the brain that allow the sensing of chromatic contrast and color vision.

Adaptation, Physiological↗

Morphology of human retinal ganglion cells with intraretinal axon collaterals.

Ganglion cells with intraretinal axon collaterals have been described in monkey (Usai et al., 1991), cat (Dacey, 1985), and turtle (Gardiner & Dacey, 1988) retina. Using intracellular injection of horseradish peroxidase and Neurobiotin in in vitro whole-mount preparations of human retina, we filled over 1000 ganglion cells, 19 of which had intraretinal axon collaterals and wide-field, spiny dendritic trees stratifying in the inner half of the inner plexiform layer. The axons were smooth and thin (approximately 2 microm) and gave off thin (<1 microm), bouton-studded terminal collaterals that extended vertically to terminate in the outer half of the inner plexiform layer. Terminal collaterals were typically 3-300 microm in length, though sometimes as long as 700 microm, and were present in clusters, or as single branched or unbranched varicose processes with round or somewhat flattened lobular terminal boutons 1-2 microm in diameter. Some cells had a single axon whereas other cells had a primary axon that gave rise to 2-4 axon branches. Axons were located either in the optic fiber layer or just beneath it in the ganglion cell layer, or near the border of the ganglion cell layer and the inner plexiform layer. This study shows that in the human retina, intraretinal axon collaterals are associated with a morphologically distinct ganglion cell type. The synaptic connections and functional role of these cells are not yet known. Since distinct ganglion cell types with intraretinal axon collaterals have also been found in monkey, cat, and turtle, this cell type may be common to all vertebrate retinas.

Axons↗

Morphology of wide-field, monostratified ganglion cells of the human retina.

To determine the number of wide-field, monostratified ganglion cell classes present in the human retina, we analyzed a large sample of ganglion cells by intracellular staining in an in vitro, whole-mount preparation of the retina. Over 1000 cells were labeled by horseradish peroxidase or Neurobiotin; some 200 cells had wide dendritic trees narrowly or broadly stratified within either the inner (ON) or outer (OFF) portion of the inner plexiform layer. Based on dendritic-field size and the pattern and extent of dendritic branching, we have distinguished six wide-field cell groups. The giant very sparse ganglion cells included both inner and outer stratifying cells and were unique both for their extremely large dendritic field (mean diameter = 1077 microm) and extremely sparsely branched dendrites. Four of the cell groups had similarly large dendritic fields, ranging in mean diameter from 737 to 791 microm, but differed in the pattern and extent of dendritic branching, with the number of dendritic branch points ranging from a mean of 33 to 129. Of these four groups, the large very sparse group and the large dense group included both inner and outer stratifying cells, while the large sparse and large moderate groups consisted of inner stratifying cells only. The thorny monostratified ganglion cells were distinct from the other cells in having medium size dendritic fields (mean diameter = 517 microm) and moderately branched, inner stratifying dendritic trees with many thin, spiny, twig-like branchlets. All six groups had medium-size cell bodies, with mean soma diameters ranging from 17 to 21 microm. Though the physiological properties and central projections of human wide-field, monostratified ganglion cells are not known, some of the cells resemble macaque ganglion cells known to project to the lateral geniculate nucleus, the pretectum, or the superior colliculus.

Adolescent↗

Apoptosis of inner hair cells caused by laser ablation of their spiral ganglion neurons in cultures of the mouse organ of Corti.

Laser beam ablation of spiral ganglion neurons was performed in seven organotypic cultures of the newborn mouse cochlea between 5 and 8 days in vitro, with a recovery period of from 18 hours to 3 days. Direct somatic injury (laser or mechanical) inflicted on hair cells does not necessarily cause their death; many of them survive, repair damage and re-establish their neurosensory connections. By contrast, laser irradiation and ablation of their afferent spiral ganglion neurons causes a most spectacular degeneration of sensory cells within 18-48 hours after the insult. Ultrastructurally, the degenerated hair cells-characteristically the inner hair cells-display "dark-cell vacuolar degeneration" that combines the signs of apoptotic death (the peripheral condensation of nuclear chromatin and nuclear pyknosis) with signs of cell edema, vacuolization and necrosis. The ultimate condensation of the cytoplasm gives the dead cells a jet black appearance. The irradiated spiral ganglion neurons die displaying similar pathological characteristics. The extent and locus of inner hair cell degeneration correspond to that of ablated spiral ganglion neurons: ultimately the ablation of one neuron causes degeneration of a single inner hair cell within the closest radial segment of the afferent innervation. The elimination of spiral ganglion neurons by mechanical means does not affect hair cell survival. It is inferred that the laser pulse acts as a stimulus depolarizing the neuronal membrane of the spiral ganglion neurons and their radial fibers and causing the excitotoxic death of their synaptic sensory cells through excessive stimulation of the glutamatergic receptors. Reciprocal pre-and postsynaptic synapses between the afferent dendrites and inner hair cells in culture could possibly serve as entryways of the stimulus. The pathogenesis of this apparent transsynaptically-induced apoptotic death of inner hair cells will be further examined in culture.

Animals↗

On the gross anatomy of the cranial cervical ganglion of the donkey (Equus asinus) in Turkey.

The cranial cervical ganglion comprises neurons of especial functional importance for the head. Six specimens of heads of adult donkeys of both sexes, all of which had been exsanguinated and perfused with 10% neutral formalin for teaching purposes, were dissected to derive a gross description of the location, arrangement and branches of the cranial cervical ganglion (ganglion cervicale craniale) bilaterally. The ganglion was irregular fusiform-shaped or flattened, and reddish-grey in colour. It was 1.9-2.1 mm in length and 0.7-0.8 mm in thickness. The ganglion was located beneath the mandibular gland, caudal to the ramus of the mandible and diverticle of the guttural pouch, and ventral to the atlanto-axial joint. The branches of the ganglion were the internal and external carotid nerves, the jugular nerve, and a branch communicating with the ventral branch of the first cervical nerve fibres.

Animals↗

Absence of spectrally specific lateral inputs to midget ganglion cells in primate retina.

Visual information is conveyed to the brain by the retinal ganglion cells. Midget ganglion cells serve fine spatial vision by summing excitation from a receptive field 'centre', receiving input from a single cone in the central retina, with lateral inhibition from a receptive field 'surround', receiving input from many surrounding cones. Midget ganglion cells are also thought to serve colour opponent vision because the centre excitation is from a cone of one spectral type, while the surround inhibition is from cones of the other type. The two major cone types, middle(M)- and long-(L)wavelength sensitive, are equally numerous and randomly distributed in the primate central retina, so a spectrally homogeneous surround requires that the cells mediating lateral interactions (horizontal or amacrine cells) receive selective input from only one cone type. Horizontal cells cannot do this because they receive input indiscriminately from M and L cones. Here we report that the amacrine cells connected to midget ganglion cells are similarly indiscriminate. The absence of spectral specificity in the inhibitory wiring raises doubt about the involvement of midget ganglion cells in colour vision and suggest that colour opponency may instead be conveyed by a different type of ganglion cell.

Animals↗

Trigeminal nerve ganglion stimulation-induced neurovascular reflexes in the anaesthetized cat: role of endothelin(B) receptors in carotid vasodilatation.

1. The effects of intravenous administration of endothelin (ET) receptor antagonists SB-209670 (0.001-10.0 mg kg(-1)), SB-217242, SB-234551 (0.01-10.0 mg kg(-1)) and BQ-788 (0.001-1.0 mg kg(-1)) were investigated on trigeminal nerve ganglion stimulation-induced neurovascular reflexes in the carotid vasculature of the anaesthetized cat. Comparisons were made with sumatriptan (0.003-3.0 mg kg(-1)) and alpha-CGRP8-37 (0.001-0.1 mg kg(-1)). 2. Trigeminal nerve ganglion stimulation produced frequency related increases in carotid blood flow, reductions in carotid vascular resistance and non-frequency related increases in blood pressure. Guanethidine (3 mg kg(-1), i.v.) blocked trigeminal nerve ganglion-induced increases in blood pressure but had no effect on changes in carotid flow or resistance. Maximal reductions in carotid vascular resistance was observed at 10 Hz, and this frequency was selected to investigate the effects of drugs on trigeminal nerve ganglion stimulation-induced responses in guanethidine treated cats. 3. Saline, alpha-CGRP8-37 SB-209670 and BQ-788 had little or no effect on resting haemodynamic parameters. SB-217242 (10 mg kg(-1), n=3) produced a 56% reduction in arterial blood pressure whereas SB-233451 (10 mg kg(-1), n=3) produced a 30% reduction in carotid vascular resistance. Sumatriptan produced dose-related reductions in resting carotid flow and increases (max. 104% at 0.3 mg kg(-1), n = 5) in vascular resistance. 4. SB-209670 (n=6-7), SB-217242 (n=3) and BQ-788 (n=3) produced inhibition of trigeminal nerve ganglion stimulation-induced reductions in carotid vascular resistance. Saline, SB-234551, alpha-CGRP8-37 and sumatriptan had no effect. 5. These data demonstrate ET(B) receptor blockade attenuates the vasodilator effects of trigeminal nerve ganglion stimulation in the carotid vascular bed of guanethidine pretreated anaesthetized cats.

Anesthesia↗

Dose-dependent rescue of axotomized rat retinal ganglion cells by adenovirus-mediated expression of glial cell-line derived neurotrophic factor in vivo.

Adult rat retinal ganglion cells undergo degeneration after optic nerve transection. Repeated intraocular injection of glial cell-line derived neurotrophic factor (GDNF) has been shown to be efficient in enhancing retinal ganglion cell survival following optic nerve axotomy. In the present study we evaluated the potential survival-promoting effect of adenovirally administered GDNF on axotomized retinal ganglion cells. A single intravitreal injection [7 x 107 plaque-forming units (pfu) or 7 x 108 pfu] of an adenoviral vector expressing the rat GDNF gene from a cytomegalovirus promoter enhanced retinal ganglion cell survival 14 days after axotomy by 67 and 125%, respectively, when compared to control animals. Intraocular administration of the vector rescued 12.6 and 23%, respectively, of the retinal ganglion cells which would otherwise have died after axotomy. An increase in retinal GDNF protein and specific virally transduced GDNF mRNA expression was detected following intraocular vector application. Our data support previous findings showing that adenoviral delivery of neurotrophic factors to the vitreous body is a feasible approach for the prevention of axotomy-induced retinal ganglion cell death in vivo and may constitute a relevant strategy for future treatment in traumatic brain injury and ensuing neurodegeneration.

Animals↗

[Neurotrophic factors of the GDNF family and their receptors are detectable in spiral ganglion cells of normal hearing as well as of deafened rats].

BACKGROUND: Recent studies have shown that neurotrophic factors like BDNF, NT-3 and GDNF induce protective effects on spiral ganglion cells after noise- or drug-induced hearing loss. According to these studies it is suggested that deafness leads to a lack of neurotrophic factor or relating receptor expression in spiral ganglion cells, that has to be compensated by local cochlear application of these factors. METHODS: In the present study we examined the expression pattern of members of the GDNF family (GDNF, Neurturin, Artemin, Persephin) and their relating receptors (Ret, GFRalpha1 - 3) as well as BDNF and trkB on spiral ganglion cells of normal hearing and experimentally deafened rats (10 % neomycine). Indirect immunofluorescence was carried out to determine protein expression of these factors and their receptors 26 days following deafening. RESULTS: Our results demonstrate neurotrophic factor and receptor expression on spiral ganglion cells of normal hearing as well as experimentally deafened animals. CONCLUSIONS: Our data indicate that within a period of 26 days after deafening no detectable reduction of the GDNF-family member expression and their receptors was ascertainable on spiral ganglion cells by immunohistochemistry. Thus, a lack of neurotrophic factor expression is unlikely to be the only cause of spiral ganglion cell loss following deafening.

Animals↗

Retinal ganglion cells are autonomous circadian oscillators synthesizing N-acetylserotonin during the day.

Retinal ganglion cells send visual and circadian information to the brain regarding the environmental light-dark cycles. We investigated the capability of retinal ganglion cells of synthesizing melatonin, a highly reliable circadian marker that regulates retinal physiology, as well as the capacity of these cells to function as autonomous circadian oscillators. Chick retinal ganglion cells presented higher levels of melatonin assessed by radioimmunoassay during both the subjective day in constant darkness and the light phase of a light-dark cycle. Similar changes were observed in mRNA levels and activity of arylalkylamine N-acetyltransferase, a key enzyme in melatonin biosynthesis, with the highest levels of both parameters during the subjective day. These daily variations were preceded by the elevation of cyclic-AMP content, the second messenger involved in the regulation of melatonin biosynthesis. Moreover, cultures of immunopurified retinal ganglion cells at embryonic day 8 synchronized by medium exchange synthesized a [3H]melatonin-like indole from [3H]tryptophan. This [3H]indole was rapidly released to the culture medium and exhibited a daily variation, with levels peaking 8 h after synchronization, which declined a few hours later. Cultures of embryonic retinal ganglion cells also showed self-sustained daily rhythms in arylalkylamine N-acetyltransferase mRNA expression during at least three cycles with a period near 24 h. These rhythms were also observed after the application of glutamate. The results demonstrate that chick retinal ganglion cells may function as autonomous circadian oscillators synthesizing a melatonin-like indole during the day.

Animals↗

Greater sensitivity of larger retinal ganglion cells to NMDA-mediated cell death.

Glutamate toxicity in retinal ganglion cells has well documented both in vitro and in vivo, and has been suggested to play a role in the neuronal loss in glaucoma. Of note, glaucoma selectively damages larger retinal ganglion cells first, and we therefore sought to explore whether glutamate-mediated cell death was likewise more pronounced in larger retinal ganglion cells. We now report that glutamate--which exerts its toxic effect on neurons predominantly through the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor--is more toxic to larger retinal ganglion cells both in tissue culture and in the intact rat eye. Cells smaller than 10 microns were relatively unaffected by glutamate or NMDA. These agents are, however, markedly toxic to retinal ganglion cells larger than 10 microns. These observations indicate that glutamate-mediated loss is seen first in larger retinal ganglion cells, in a similar fashion to the pattern of loss seen in glaucoma.

Animals↗

Broad spectrum caspase inhibitor rescues retinal ganglion cells after ischemia.

Following ischemia/reperfusion the death of retinal ganglion cells in adult Wistar rat retina continues for weeks. Using new, more stable caspase inhibitor, Q-VD-OPH we studied its neuroprotective effect on identifiable retinal ganglion cells after 75 min ischemia followed by reperfusion. Q-VD-OPH was injected intravitreally 48 h after ischemia/reperfusion. Retinal ganglion cells were labeled by intratectal injection of Fluorogold and cells were counted on flat mounted retinas. Retinal ganglion cells survival increased after 2 and 3 weeks of ischemia/reperfusion in Q-VD-OPH injected eyes. We studied apoptotic cell death by immunocytochemically labeling retina with cleaved Poly (ADP-ribose) polymerase (PARP). Labeling for cleaved PARP remained elevated in the ganglion cell layer and inner nuclear layer after 1,2and 3 weeks of ischemia/reperfusion. Administration of Q-VD-OPH significantly reduced the labeling for cleaved PARP in the retina and increased the survival of retinal ganglion cells.

Animals↗

Branching of spiral ganglion neurites is induced by focal application of fibroblast growth factor-1.

OBJECTIVES/HYPOTHESIS: During the terminal innervation of the developing organ of Corti, fibroblast growth factor-1 (FGF-1) messenger RNA has been shown to be transiently expressed in the sensory epithelium of the rat, suggesting that this growth factor may contribute to developmental processes such as innervation and synaptogenesis of the inner and outer hair cells. In a previous study it has been demonstrated that exogenous FGF-1 supports rat spiral ganglion neurite extension in vitro, whereas a secreted form of FGF-1 produced by transfected fibrocytes induces neurite branching and targeting. STUDY DESIGN: Response of spiral ganglion neurites to FGF-1-coupled beads was compared with the response to noncoupled control beads. METHODS: Effects of multiple focal sources of FGF-1 to outgrowing spiral ganglion neurites were investigated on explants from postnatal day 4 rat spiral ganglion samples that were cultured in the presence of FGF-1 covalently coupled to polybead microspheres. After fixation and immunocytochemical labeling of the explants the growth patterns of the extending neuronal processes were evaluated. RESULTS: When spiral ganglion neurites were observed near clusters of FGF-1 beads, they formed a plexus-like network characterized by significantly higher branching in the vicinity of the beads. However, fibers did not appear to terminate on the beads. Plexus-like formations were not seen at a distance from FGF-1 coupled beads or in the vicinity of control beads lacking FGF-1 on their surface. CONCLUSION: The results of the study indicate that spiral ganglion neurites branch in response to focal sources of FGF-1, suggesting an important role of this growth factor for hair cell innervation during the terminal development of the sensory epithelium.

Animals↗

Long-term effect of retinal ganglion cell axotomy on the histomorphometry of other cells in the porcine retina.

PURPOSE: To determine the effect of retinal ganglion cell axotomy on the thickness of inner plexiform, inner nuclear, and outer plexiform layers, as well as the densities of short- and middle-to-long-wavelength cones, in the porcine retina. METHODS: Unilateral retinal ganglion cell axotomy was performed in seven domestic pigs by either surgical optic nerve section or peripapillary argon laser photocoagulation. Damage to the retinal vasculature was ruled out with fluorescein angiography. Histologic examination of the retinal tissue was performed nine months later. Cone densities were determined immunohistochemically with the anti-visual pigment antibodies COS-1 and OS-2. Image analysis of semithin retinal cross sections was used to measure the thickness of the retinal layers. The effect of axotomy was quantified by optic nerve axon counts and estimations of retinal ganglion cell counts. The data were compared between the eyes with axotomy and the contralateral normal eye using the nonparametric Wilcoxon rank sum test. RESULTS: Treatment of the peripapillary retina with the argon laser resulted in a median decrease in axon counts and retinal ganglion cell density estimates of 31%. No optic nerve axons and cells resembling retinal ganglion cells were found in the eyes with transected optic nerves. There was no significant difference in either the thickness of any retinal layers or cone densities between axotomized and normal control eyes. CONCLUSION: No signs of retrograde transsynaptic degeneration were observed in porcine retinas nine months after retinal ganglion cell axotomy.

Animals↗

Birth dates of retinal ganglion cells giving rise to the crossed and uncrossed optic projections in the mouse.

In the mouse, as in most mammals, the crossed optic projections originate from the entire extent of the retina, whereas ganglion cells giving rise to the uncrossed (ipsilateral) projection are restricted to the temporal and ventral retina. The nasal border of this bilaterally projecting region in the retina corresponds to the midline of the visual field. Here the birth dates of ipsilaterally and contralaterally projecting ganglion cells were determined by combining tritiated thymidine labelling in the embryo with horseradish peroxidase tracings from the optic tract in the adult. Contralaterally projecting ganglion cells were found to be generated from embryonic day E11 to about E19 in a crude concentric fashion with the oldest cells in central and youngest ones in peripheral retina. Ipsilaterally projecting cells were born from E11 to E16, that is, during the earlier part of the period in which the contralateral projection was born. At the earliest time of ganglion cell generation (E11-12) ipsi- and contralaterally projecting cells were born within separate retinal regions, with the future midline representation forming the border between the two zones. This distinction became lost after E13, when both ipsi- and contralaterally projecting cells were born in the bilaterally projecting region. Hence at E11-12 the retina was found to have a bipartite organization that may allow the specification of the two maps of opposite topographical polarity in which the crossed and uncrossed projections are organized. Since in the adult retina this bipartite organization is preserved only in the large ganglion cells that project to the lateral geniculate nucleus, and since large ganglion cells are known to be the earliest ones formed in the mouse, these cells may be the ones that establish the early and bilateral projections of the retina. The conclusion that the bilateral projection system in the retina reflects an early developmental programme, and not the result of competition between the two eyes at later stages, was reinforced by observing a practically normal retinal origin of ipsilateral projections in mice which had only one normal eye from the earliest stages of eye development.

Animals↗