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At least 1,297 records · Page 72Linked to original sources
PubMed1990

Dissection of the neuron network in the catfish inner retina. IV. Bidirectional interactions between amacrine and ganglion cells.

1. We have functionally dissected the neuron network in the catfish inner retina by means of current injection. Simultaneous intracellular recordings were made from two neighboring neurons with the use of two separate electrodes. Extrinsic current was injected into one neuron, and the resulting intracellular responses were recorded from the other neuron. The test signals included 1) a single-frequency sinusoid, 2) a depolarizing or a hyperpolarizing current pulse, and 3) white-noise modulated current from which Wiener kernels were computed by an input-output cross-correlation process. 2. Extrinsic current injected into an ON amacrine (NA) cell evoked responses from a neighboring ON ganglion (GA) cell. Conversely, current injected into a GA cell elicited responses from a neighboring NA cell. Similar results were obtained for the transmission between OFF amacrine (NB) and OFF ganglion (GB) cells. Neural filters for the forward and backward transmissions between amacrine and ganglion cells of the same response polarity were low-pass, constant gain with a cutoff frequency of 40-50 Hz. The gain measured by current-amplitude relationships was comparable for the forward (N----G) and backward (G----N) transmission. 3. Similar bidirectional signal transmission was found between amacrine cells and between ganglion cells of the same response polarity. Neural filters for such transmission were also low-pass, constant gain with a cutoff frequency of 40-50 Hz. 4. Because a large portion of the current-evoked response was predicted by the first-order kernel, transmission between cells of the same response polarity was approximately linear. The current-evoked first-order kernels were brief and impulse-like compared with the light-evoked first-order kernels. 5. We conclude that ON and OFF amacrine and ganglion cells form two ON- and OFF-cell clusters in which cells are extensively and bidirectionally interconnected, enhancing the response in each cluster.

Animals↗
PubMed1991

Calcium ion levels in resting and depolarized goldfish retinal ganglion cell somata and growth cones.

1. We have estimated free, intracellular calcium ion concentrations ([Ca]i) in isolated retinal ganglion cells of adult goldfish by ratio-imaging fura-2 emission intensity at two excitation wavelengths. Here we describe [Ca]i in these cells, both at rest and during depolarization by elevated levels of extracellular potassium ions ([K]o). 2. [K]o was varied between 5 and 60 mM in sodium-free, tetrodotoxin-containing salines. Ganglion cell membrane potential, measured with patch electrodes, fell with each increment of [K]o used, from approximately -70 mV in 5 mM K+ to approximately -20 mV in 60 mM K+. 3. In control saline, [Ca]i was roughly 120 nM in cell somata and at least twofold higher in their growth cones. [Ca]i increased in both somata and growth cones to as high as 1.5 microM in salines containing 60 mM K+. [Ca]i exceeded 1.5 microM in some cells in high-K+ salines, although these levels could not be quantified accurately with fura-2. 4. Increases in [Ca]i elicited by elevated [K]o persisted for the duration of the exposure to high-K+ saline and were blocked by replacement of most of the bath Ca2+ by Co2+. These increases in [Ca]i were also sensitive to dihydropyridine calcium-channel ligands, viz., enhanced by BAY K 8644 (3 microM) and antagonized by nifedipine (10 microM). 5. Partial recovery of control [Ca]i occurred when [K]o was reduced to 5 mM after exposure to high-K+ saline and in high-K+ saline when nifedipine was included. These results show that goldfish retinal ganglion cells can partially buffer intracellular Ca2+ in the absence of extracellular Na+ ions. 6. These results provide measurements of the changes in [Ca]i brought about by depolarization of goldfish retinal ganglion cells in Na(+)-free salines. In these salines, at least part of the increase in [Ca]i appears to result from Ca2+ influx through a voltage-activated, noninactivating calcium conductance in the somata and growth cones of these cells. These measurements complement whole-cell patch-clamp and vibrating microprobe recordings from the somata and neurites of these cells and also immunocytochemical studies and patch-clamp measurements in amphibian, reptilian, and mammalian retinal ganglion cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Identification of glutamate receptor subtypes mediating inputs to bipolar cells and ganglion cells in the tiger salamander retina.

1. The effects of glutamate receptor agonists and antagonists on bipolar cells and ganglion cells were studied with the use of intracellular and extracellular recording in the superfused, isolated, flat-mounted tiger salamander retina. The goal of the experiments was to correlate glutamate receptor subtypes with their localization at specific synaptic sites in the tiger salamander retina. The drugs tested were the kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the N-methyl-D-aspartate (NMDA) receptor antagonist 3-(C+/-)-2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid (CPP) and L-2-amino-4-phosphonobutyrate (L-AP4). 2. The light responses of hyperpolarizing bipolar cells were suppressed by 20 microM CNQX, whereas L-AP4 had no effect on their light responses. In contrast, 20 microM CNQX had no effect on depolarizing bipolar cells, whereas L-AP4 abolished the light responses of these cells. 3. The light offset responses of OFF and ON-OFF ganglion cells were completely blocked by concentrations of CNQX as low as 5 microM. The light onset responses of ON-OFF ganglion cells were blocked when the concentration of CNQX was raised to 20 microM. In addition, 30 microM CPP partially blocked the light onset responses of ON-OFF ganglion cells but had a lesser effect on the light offset responses. 4. Twenty micromolars of CNQX blocked a transient component, and 20 microM CPP blocked a sustained component of the light response of sustained-ON ganglion cells.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

Calcium currents in turtle retinal ganglion cells. II. Dopamine modulation via a cyclic AMP-dependent mechanism.

1. Voltage-activated calcium currents participate in shaping the firing pattern of neurons. Calcium currents also have a role in signal transduction. In the retina, little is known of the regulation of calcium entry into neurons via voltage-activated channels. In the present series of experiments we used standard whole cell and perforated patch clamp techniques to study the ability of the neurotransmitter dopamine (DA) to modulate voltage-dependent calcium currents in isolated turtle retinal ganglion cells. 2. Two types of calcium current have been described in these cells, one transient and the other sustained. Here we focused our studies primarily on the sustained current (ICa). Exogenous DA reduced ICa in some cells (59%), facilitated ICa in others (17%), or had no effect on the remainder (24%). Regardless of the action of DA, there was no effect on the voltage dependence of ICa. In addition, the effects were all reversible. The average magnitude of decrease was 43%, whereas that of increase was 75%. 3. The application of a specific D1 receptor agonist, SKF38393, mimicked the effect of DA. This was also true for a membrane permeable cyclic AMP (cAMP) analogue (8-CPT-cAMP). Inhibition of protein kinase A (PKA) activity by a specific inhibitor, IP20-amide, injected into cells prevented the modulatory effects of DA on ICa. 4. Immunocytochemical studies demonstrated that DA stimulation of the retina significantly increased the level of cAMP immunoreactivity in peripheral ganglion cells, whereas those cells in central retina were less affected. Forskolin induced a general elevation of cytoplasmic cAMP staining in all ganglion cells. 5. Current clamp experiments were carried out to determine the role of the calcium currents in action potential generation. Both the sustained and transient currents participated in the shaping of current-induced firing patterns of isolated cells. Depolarizing current-induced spiking of ganglion cells was found to be highly modified by dopamine. 6. These results support the notion that endogenous DA modulates the conductance of voltage-dependent calcium channels in turtle retinal ganglion cells and that this modulation is mediated by a D1 dopamine receptor-cAMP-PKA pathway. The direct result of this modulation is an alteration in the signaling properties of certain cells.

Animals↗
PubMed1994

Na(+)-Ca2+ exchanger-like immunoreactivity and regulation of intracellular Ca2+ levels in fish retinal ganglion cells.

1. We have used two experimental approaches to examine regulation of intracellular calcium ion levels in fish retinal ganglion cells. In the first set of experiments, we ratio-imaged fura-2 emission intensity to estimate the concentration of free intracellular calcium ions ([Ca2+]i) in isolated goldfish retinal ganglion cells depolarized by increases in extracellular levels of potassium ions ([K+]o), in the presence and absence of extracellular sodium ions (Na+). Stepwise increases in [K+]o from 5 mM to as high as 60 mM produced stepwise increases in [Ca2+]i. These increases were sustained in the absence of external Na+, but transient and smaller in the presence of external Na+. The decline of [Ca2+]i in high-K, Na(+)-containing saline could be reversed by application of the ionophore monensin, or by replacement of external Na+ with either N-methyl-D-glucamine or lithium. In Na(+)-containing saline, [Ca2+]i fell to control levels after [K+]o was restored to control levels. 2. In the second set of experiments, we assessed Na(+)-Ca2+ exchanger-like immunoreactivity in goldfish retinal ganglion cells with the use of a polyclonal antiserum directed against Na(+)-Ca2+,K+ exchanger purified from bovine rod outer segments. This antiserum specifically stained the somata, neurites, and growth cones of isolated ganglion cells, the outer segments of rod photoreceptors, and (on Western blots prepared from mechanically isolated rods) protein displaying an apparent molecular mass of 210 kDa. 3. These results provide measurements of changes in [Ca2+]i of retinal ganglion cells depolarized in Na(+)-containing saline, and the distribution and apparent molecular weight of Na(+)-Ca2+ exchanger-like immunoreactivity in teleost retina.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Developmental characteristics of the chick nodose ganglion.

Morphometric studies were carried out on the chick nodose ganglion between day 5 of incubation and 2 weeks after hatching. Previous findings showed that ablation of the nodose placode, the locus of precursor cells of nodose ganglion sensory neurons, results in abnormal cardiac function, and that these precursors can be induced to migrate abnormally to the heart and express abnormal phenotypes there, following cardiac neural crest ablation. These results prompted us to investigate further the normal development of nodose ganglion neurons. We find that the major period of neuron generation from placodal precursor cells in the ganglion occurs prior to day 5 of incubation. The loss of more than half of these neurons takes place between embryonic days 5 and 20, while neuron and ganglion sizes increase dramatically. Myelination is not seen at day 12 of incubation, but is present on day 15. Neurons continue to develop after hatching (day 21), reaching their adult size by 2 weeks after hatching. Unexpectedly, we found that the number of neurons increases after hatching, reaching the adult level of 62% more than embryonic day-20 numbers by 2 weeks after hatching. The mechanisms underlying the increase in neuron number after hatching are unexplained and require further investigation.

Analysis of Variance↗
PubMed1978

Electron-microscopic analysis of the mouse facial nerve near the geniculate ganglion.

An electron-microscopic analysis of the mouse facial nerve near the geniculate ganglion shows that there are, on the everage, 603 more nerve fibers in the portion of the nerve distal to the geniculate ganglion than there are in the part proximal to the ganglion. The average distal increase in the number of unmyelinated fibers is 444 and that in the myelinated fibers is 165. The somatic motor nerve fibers and the parasympathetic fibers in the mouse facial nerve may not contribute to the distal excess. It is possible that the increase in the number of unmyelinated fibers distal to the geniculate ganglion is mainly due to the presence of postganglionic sympathetic fibers in the facial trunk distal to the geniculate ganglion and the greater petrosal nerve. The distal increase in the number of myelinated fibers may be mainly contributed by the sensory fibers.

Animals↗
PubMed1984

Relations between the human retinal cone and ganglion cell distribution.

The distribution of human cone cells is well known and is frequently cited. The distribution of human ganglion cells is less well known and was published in a booklet which is less frequently cited in the eye literature. Selected published curves provided by these authors and Snellen acuity data were digitally encoded, transformed to linear vertical axes where necessary, scaled and compared. Comparisons were possible along the temporal hemi-meridian and provided correlations (r = 0.99 for ganglion cells versus cone cells; r = 0.99 for ganglion cells versus acuity, and r = 0.98 for cone cells versus acuity). Integration of densities along the horizontal hemi-meridian out to 50 degrees showed that approximately 50% of the cone cells are within 18 degrees of the foveola and that approximately 50% of the ganglion cells are within 13 degrees of the foveola. Appreciation of the strong interrelations between the cone-ganglion cell distributions may provide for a better understanding of the visual of inner-retinal disease. Presently it accounts for aspects of the production of pattern-elicited retinal signals which are under intense investigation in many centers.

Humans↗
PubMed2003

Peripheral resolution for achromatic and SWS gratings in early to moderate glaucoma and the implications for selective ganglion cell density loss.

PURPOSE: To investigate whether there is significant selective reduction in short-wavelength-sensitive (SWS) ganglion cell density in early to moderate glaucoma. METHODS: Peripheral achromatic resolution acuity (an indirect measure of the underlying midget ganglion cell density) and peripheral chromatic resolution acuity under conditions of blue cone isolation (an indirect measure of the underlying small bistratified ganglion cell density) were measured at 13 degrees eccentricity in four oblique meridians in 15 eyes (mean age, 64.6 +/- 9.6 years) with early to moderate glaucoma. The results from the subjects with glaucoma were compared with those in a group of 17 age-matched normal eyes (mean age, 62.5 +/- 6.6 years). RESULTS: Mean achromatic resolution acuity across the four locations was significantly lower in the subjects with glaucoma than in the normal subjects (2.92 vs. 4.01 cyc/deg). Mean chromatic resolution acuity across the four locations was also significantly lower in the subjects with glaucoma than the normal subjects (0.78 vs. 0.99 cyc/deg). There was no selective loss of mean SWS acuity in the subjects with glaucoma. Individual location analysis revealed that the chromatic-achromatic resolution ratio was not significantly different in the subjects with glaucoma who had early glaucomatous damage when compared with the normal subjects. The chromatic-achromatic resolution ratio was lower than normal at certain locations in certain individuals with early glaucoma. CONCLUSIONS: The results indicate that there is no evidence of significant selective reduction in global SWS ganglion cell density in early to moderate glaucoma. However, there may be selective loss of SWS ganglion cell density at individual locations in individual eyes.

Aged↗
PubMed2005

Flavonoids protect retinal ganglion cells from oxidative stress-induced death.

PURPOSE: Mounting evidence suggests that oxidative stress contributes to the pathogenesis of many ocular diseases, including glaucoma and diabetic retinopathy. No treatments are available to prevent the neuronal degeneration that occurs in these disorders. The purpose of this study was to determine whether flavonoids, natural products that are abundant in fruits and vegetables, can protect retinal ganglion cells from oxidative stress-induced death. METHODS: The ability of flavonoids to protect an immortalized retinal ganglion cell line, RGC-5 cells, was tested using three model systems of oxidative stress-induced cell death: glutathione (GSH) depletion, t-butyl peroxide (t-BOOH) treatment, and hydrogen peroxide (H2O2) treatment. RESULTS: GSH depletion causes retinal ganglion cell death by a pathway involving the production of endogenous reactive oxygen species (ROS), whereas the other two treatments use exogenous sources of ROS. It was found that specific flavonoids could protect retinal ganglion cells from cell death initiated by all three of the inducers of oxidative stress with high levels of potency and low toxicity. In the case of GSH depletion, different flavonoids could be shown to act at distinct steps in the cell death pathway. Several of the protective flavonoids also induced the synthesis of the transcription factor NF-E2-related factor 2 and phase 2 antioxidant enzymes such as heme oxygenase 1, markers for the activation of the antioxidant response element. CONCLUSIONS: These results suggest that certain flavonoids can function as potent and effective neuroprotective agents for retinal ganglion cells.

Animals↗
PubMed2006

Visual response properties of retinal ganglion cells in the royal college of surgeons dystrophic rat.

PURPOSE: Alterations in retinal ganglion cell response patterns were profiled in dystrophic Royal College of Surgeons (hereafter RCS) rats over the first 100 postnatal days as a baseline for retinal rescue and vision restoration strategies. This method enabled the evaluation of the extent to which postreceptoral neuronal attributes in degenerating retinas mirror inferred declines in photoreceptor function. METHODS: Single-unit responses from large retinal ganglion cells were recorded from age-matched dystrophic RCS (RCS-rdy(-)) and congenic RCS-p(+) (hereafter wild-type or wt) rats were recorded in vitro under visual control. Cells were profiled with conventional spatial and flux stimulus modulations. RESULTS: Ganglion cell single unit and population attributes alter slowly over the course of photoreceptor degeneration in dystrophic RCS rats, with significant decreases in apparent receptive field size, contrast sensitivity, and threshold sensitivity detected by the first month of life. Spatial frequency tuning and contrast responses were extremely weak by postnatal day (P)76, paralleled by a progressive decline in signal-to-noise (S-N) ratio to roughly unity by postnatal day (P)107. This decline was only a simple loss of responsivity, as background firing rates increased substantially over time. Whereas wt retinas were dominated by ON-center cells (15/23 cells), dystrophic animals were dominated by OFF-center cells by P47 (24/27 cells). CONCLUSIONS: The first definitive signs of degeneration in dystrophic RCS rats are parallel decreases in ganglion cell threshold sensitivity and receptive field size, followed by deterioration in spatial summation. Arguably, these changes can be qualitatively explained as photoreceptor signaling losses. However, the apparent shift in population profile from ON- to OFF-center ganglion cells long before loss of the b-wave at P90 implies that a reactive mechanism such as bipolar cell rewiring and/or transformation of neuronal phenotypes occur during the early phase of photoreceptor stress, before rod and cone death.

Animals↗
PubMed2002

The three faces of vestibular ganglionitis.

We present temporal bone and clinical evidence that common syndromes of recurrent vertigo are caused by a viral infection of the vestibular ganglion. In the present series, histopathologic and radiologic changes in the vestibular ganglion and meatal ganglion were consistent with a viral inflammation of ganglion cells in cases of Meniere's disease, benign paroxysmal positional vertigo, and vestibular neuronitis. Clinical observations of multiple neuropathies involving cranial nerves V, VII, and VIII on the same side in patients with recurrent vertigo are best explained by a cranial polyganglionitis caused by a neurotrophic virus, which is reactivated by a stressful event later in life. The reactivation of the latent virus may manifest as one of the above vertigo syndromes, depending on the part of the vestibular ganglion that is inflamed, the type and strain of the virus, and host resistance.

Adult↗
PubMed2003

Microsurgical anatomy of the perigeniculate ganglion area as seen from the middle cranial fossa approach.

The middle cranial fossa approach is useful for decompressing the perigeniculate ganglion area of the facial nerve in patients with serviceable hearing. The present study was designed to investigate the microsurgical anatomy of the perigeniculate ganglion area of the facial nerve from the point of view of the middle cranial fossa. We dissected 20 human temporal bones under a microscope using a middle fossa approach, and measured the angle between the lines drawn from the malleus head to the vertical crest and from the malleus head to the geniculate ganglion, and the distance from the malleus head to the geniculate ganglion. These were found to be 22.7 degrees +/- 2.2 degrees and 6.5 +/- 0.3 mm, respectively. Detailed knowledge about the microsurgical anatomy of the perigeniculate ganglion area of the facial nerve from the point of view of the middle cranial fossa is imperative for facial nerve decompression by a middle cranial fossa approach.

Cranial Fossa, Middle↗
PubMed1989

Survival of spiral ganglion cells in profound sensorineural hearing loss: implications for cochlear implantation.

Ninety-three temporal bones from 66 patients who were profoundly deaf during life were reconstructed by analysis of serial light microscopic sections. The correlations of total and segmental spiral ganglion cell counts with age, duration of hearing loss and profound deafness, and cause of hearing loss were evaluated. Bivariate analysis demonstrated that total spiral ganglion cell count tended to be lower in older than in younger deaf individuals and lower with longer duration of hearing loss and total deafness. However, multiple regression analysis demonstrated that the cause of hearing loss was the single most significant determinant of total spiral ganglion cell count. Patients with deafness due to aminoglycoside toxicity or sudden idiopathic deafness had the highest residual spiral ganglion cell count and patients with deafness due to presumptive postnatal viral labyrinthitis, bacterial labyrinthitis, and congenital or genetic causes had the lowest numbers of residual spiral ganglion cells.

Age Factors↗
PubMed2006

Increase of galanin in trigeminal ganglion during tooth movement.

It is known that nerve fibers containing neuropeptides such as galanin increase in the periodontal ligament during experimental tooth movement. However, the origin of galanin-containing nerve fibers in the periodontal ligament remains unclear. This study was conducted to examine our hypothesis that the increased galanin nerve fibers have a sensory neuronal origin, and that the peptide is associated with pain transmission and/or periodontal ligament remodeling during experimental tooth movement. In control rats, galanin-immunoreactive trigeminal ganglion cells were very rare and were observed predominantly in small ganglion cells. After 3 days of experimental tooth movement, galanin-immunoreactive trigeminal ganglion cells significantly increased, and the most marked increase was observed at 5 days after experimental tooth movement. Furthermore, their cell size spectrum also significantly changed after 3 and 5 days of movement: Medium-sized and large trigeminal ganglion cells began expressing, and continued to express, galanin until 14 days after experimental tooth movement. These findings suggest that the increase of galanin in the periodontal ligament during experimental tooth movement at least partially originates from trigeminal ganglion neurons and may play a role in pain transmission and/or periodontal remodeling.

Animals↗
PubMed2004

The homeobox gene Xbh1 cooperates with proneural genes to specify ganglion cell fate within the Xenopus neural retina.

Recent studies on vertebrate eye development have focused on the molecular mechanisms of specification of different retinal cell types during development. Only a limited number of genes involved in this process has been identified. In Drosophila, BarH genes are necessary for the correct specification of R1/R6 eye photoreceptors. Vertebrate Bar homologues have been identified and are expressed in vertebrate retinal ganglion cells during differentiation; however, their retinal function has not yet been addressed. In this study, we report on the role of the Xenopus Bar homologue Xbh1 in retinal ganglion cell development and its interaction with the proneural genes Xath5 and Xath3, whose ability to promote ganglion cell fate has been demonstrated. We show that XHB1 plays a crucial role in retinal cell determination, acting as a switch towards ganglion cell fate. Detailed expression analysis, animal cap assays and in vivo lipofection assays, indicate that Xbh1 acts as a late transcriptional repressor downstream of the atonal genes Xath3 and Xath5. However, the action of Xbh1 on ganglion cell development is different and more specific than that of the Xath genes, and accounts for only a part of their activities during retinogenesis.

Animals↗
PubMed1991

A chondroitin sulfate proteoglycan may influence the direction of retinal ganglion cell outgrowth.

In the developing retina, retinal ganglion cell (RGC) axons elongate toward the optic fissure, even though no obvious directional restrictions exist. Previous studies indicate that axon-matrix interactions are important for retinal ganglion cell axon elongation, but the factors that direct elongation are unknown. Chondroitin sulfate proteoglycan (CS-PG), a component of the extracellular matrix, repels elongating dorsal root ganglion (DRG) axons in vitro and is present in vivo in the roof plate of the spinal cord, a structure that acts as a barrier to DRG axons during development. In this study, we examined whether CS-PG may regulate the pattern of retinal ganglion cell outgrowth in the developing retina. Immunocytochemical analysis showed that CS-PG was present in the innermost layers of the developing rat retina. The expression of CS-PG moved peripherally with retinal development, always remaining at the outer edge of the front of the developing axons. CS-PG was no longer detectable with immunocytochemical techniques when RGC axon elongation in the retina is complete. Results of studies in vitro showed that CS-PG, isolated from bovine nasal cartilage and chick limb, was inhibitory to elongating RGC axons and that RGC growth cones were more sensitive to CS-PG than were DRG neurites tested at the same concentrations of CS-PG. The behavior of retinal growth cones as they encounter CS-PG was characterized using time-lapse video microscopy. Filopodia of the RGC growth cones extended to and sampled the CS-PG repeatedly. With time, the growth cones turned to avoid outgrowth on the CS-PG and grew only on laminin. While numerous studies have shown the presence of positive factors within the retina that may guide developing RGC axons, this is the first demonstration of an inhibitory or repelling molecule in the retina that may regulate axon elongation. Taken together, these data suggest that the direction of RGC outgrowth in the retina may be regulated by the proper ratio of growth-promoting molecules, such as laminin, to growth-inhibiting molecules, like CS-PG, present in the correct pattern and concentrations along the retinal ganglion cell pathway.

Animals↗
PubMed1995

Vertebrate retinal ganglion cells are selected from competent progenitors by the action of Notch.

The first cells generated during development of the vertebrate retina are the ganglion cells, the projection neurons of the retina. Although they are one of the most intensively studied cell types within the central nervous system, little is known of the mechanisms that determine ganglion cell fate. We demonstrate that ganglion cells are selected from a large group of competent progenitors that comprise the majority of the early embryonic retina and that differentiation within this group is regulated by Notch. Notch activity in vivo was diminished using antisense oligonucleotides or augmented using a retrovirally transduced constitutively active allele of Notch. The number of ganglion cells produced was inversely related to the level of Notch activity. In addition, the Notch ligand Delta inhibited retinal progenitors from differentiating as ganglion cells to the same degree as did activated Notch in an in vitro assay. These results suggest a conserved strategy for neurogenesis in the retina and describe a versatile in vitro and in vivo system with which to examine the action of the Notch pathway in a specific cell fate decision in a vertebrate.

Alleles↗