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Analysis of spiral ganglion cell populations in children with normal and pathological ears.

This study analyzed features of total and segmental spiral ganglion cell populations in children with normal ears and those with various pathological conditions. Sixty-three human temporal bone specimens, obtained from 43 children 4 days to 9 years of age, were studied histopathologically. These specimens were divided into 5 diagnostic groups: group 1, normal ears (13 ears); group 2, congenital infectious diseases (13 ears); group 3, chromosomal aberrations (11 ears); group 4, multiple craniofacial anomalies with hereditary or genetic causes (21 ears); and group 5, perinatal and postnatal asphyxia (5 ears). Eighteen of the 63 ears had documented profound deafness. In either normal ears (group 1) or those with various pathological conditions (groups 2 through 5), the total number of ganglion cells did not change as a function of age during the first 10 years. The total number of ganglion cells was significantly larger in group 1 (33,702) than in each of groups 2, 3, 4, and 5 (p < .01), and the number was significantly larger in group 2 than in each of groups 4 and 5 (p < .01 and p < .05, respectively). The ratio of basal to apical ganglion cell populations remained constant in both normal and pathological ears. Each ratio of the number of basal and apical ganglion cells in groups 2, 3, 4, and 5 to the mean number in group 1 (basal and apical survival ratios) was at least approximately 40%. There was no statistical difference between these two ratios in groups 2, 3, 4, and 5. The mean (+/-SD) total number of ganglion cells in ears with documented profound deafness was 15,417 +/- 5,944, which is approximately 40% of those present in normal ears. Our results suggest that normally, cochlear neurons are completely present at birth and minimally regress during the first decade of life. In addition, although intergroup differences among various pathological groups were present, the majority of pathological ears had more than 10,000 spiral ganglion cells present. Cochlear implantation has gradually been recognized as an effective and reliable tool for rehabilitation of children who have profound deafness, even congenitally or prelingually deafened children. On the basis of the results obtained in this study, we discuss the implications for cochlear implantation in children.

Age Factors↗

All Brn3 genes can promote retinal ganglion cell differentiation in the chick.

Targeted gene disruption studies in the mouse have demonstrated crucial roles for the Brn3 POU domain transcription factor genes, Brn3a, Brn3b, Brn3c (now called Pou4f1, Pou4f2, Pou4f3, respectively) in sensorineural development and survival. During mouse retinogenesis, the Brn3b gene is expressed in a large set of postmitotic ganglion cell precursors and is required for their early and terminal differentiation. In contrast, the Brn3a and Brn3c genes, which are expressed later in ganglion cells, appear to be dispensable for ganglion cell development. To understand the mechanism that causes the functional differences of Brn3 genes in retinal development, we employed a gain-of-function approach in the chick embryo. We find that Brn3b(l) and Brn3b(s), the two isoforms encoded by the Brn3b gene, as well as Brn3a and Brn3c all have similar DNA-binding and transactivating activities. We further find that the POU domain is minimally required for these activities. Consequently, we show that all these Brn3 proteins have a similar ability to promote development of ganglion cells when ectopically expressed in retinal progenitors. During chick retinogenesis, cBrn3c instead of cBrn3b exhibits a spatial and temporal expression pattern characteristic of ganglion cell genesis and its misexpression can also increase ganglion cell production. Based on these data, we propose that all Brn3 factors are capable of promoting retinal ganglion cell development, and that this potential may be limited by the order of expression in vivo.

Animals↗

Immunohistochemical demonstration of inducible nitric oxide and nuclear factor-kappa B with reference to age-related changes in the mouse spiral and vestibular ganglion.

The morphology and immunohistochemistry of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-kappa B) were studied on the spiral and vestibular ganglion of young and old ddy mice. The significant decrease in the number of the spiral ganglion cells and a significant expression of iNOS and NF-kappa B were observed in old mice. In contrast, in the vestibular ganglion of all animals examined, decrease in the number of the ganglion cells or expression of iNOS and NF-kappa B were not observed. Although the relevance of enzymatic systems for the protection of vestibular ganglion cells in old individuals from harmful oxidative stress increased with aging should be further clarified, lack of harmful stress due to nitric oxide (NO) may be one of the plausible reasons for that the vestibular ganglion cells were not decreased in number with aging, since iNOS was not detected in the vestibular ganglion cells in the animals tested in the present study.

Aging↗

Retrograde axonal transport impairment of large- and medium-sized retinal ganglion cells in diabetic rat.

PURPOSE: Several abnormalities in visual pathway functions in diabetic humans and animals have been reported. We demonstrated retrograde axonal transport impairment in retinal ganglion cells of streptozotocin-diabetic rats. METHODS: Diabetes was induced in male Wistar albino rats by intraperitoneal injection of streptozotocin. Three months after the induction of diabetes, fluoro-gold was injected into the dorsal lateral geniculate nucleus. Percentages of fluoro-gold-labeled large-, medium- and small-sized retinal ganglion cells per total population were calculated in wholemount retinas of diabetic and control rats. The same sections were stained with cresyl violet and each retinal ganglion cell type evaluated by light microscopy. RESULTS: Although a quantitative decrease in the population of each retinal ganglion cell type was not observed, mean percentages of fluoro-gold-labeled large- and medium-sized retinal ganglion cells per total population were significantly decreased in diabetic rats compared with controls. CONCLUSIONS: Our results suggest that diabetes affects the retrograde axonal transport in large- and medium-sized retinal ganglion cells despite the absence of morphological changes in the perikaryon and decrease in total cell population. Diabetes-induced impairment of retrograde axonal transport in large- and medium-sized retinal ganglion cells precede optic nerve involvement. However, this may merely be a consequence of metabolic changes in diabetic states.

Animals↗

Segregation of on and off bipolar cell axonal arbors in the absence of retinal ganglion cells.

Retinal cells that respond selectively to light onset or offset are segregated into On and Off pathways. Here, we describe the development of cone bipolar cells whose axonal arbors at maturity synapse onto ganglion cell dendrites confined to On and Off strata of the inner plexiform layer (IPL). In particular, we sought to determine whether the formation of this segregated pattern is dependent on the presence of ganglion cells. Developing bipolar cells were visualized using an antibody against recoverin, the calcium binding protein that labels On and Off cone bipolar cells in the adult rat retina. Recoverin-positive cells were apparent in the ventricular zone on the day of birth [postnatal day 0 (P0)], before bipolar cells begin to migrate to the inner nuclear layer. Two distinct strata were first apparent in the IPL at P8, with the Off pathway maturing earlier than the On pathway. There was no indication of exuberant bipolar cell projections. Throughout development, there were also a small number of recoverin-positive cells of unknown origin in the ganglion cell layer. To assess whether the formation of On and Off cone bipolar cell projections is dependent on the presence of ganglion cells, these target neurons were eliminated by unilateral section of the optic nerve. This was done on the day of birth, resulting in a total loss of ganglion cells 5-6 d before bipolar cell axons innervate the IPL. In retinas with optic nerve sections, On and Off cone bipolar cells were present, albeit at a lower than normal density, and the axonal arbors of these interneurons were organized into two distinct strata. This indicates that ganglion cells are not essential for the formation of segregated On and Off bipolar cell inputs. These results lend support to the hypothesis that specific ingrowth patterns of bipolar cell terminal arbors could regulate the formation of stratified retinal ganglion cell dendrites.

Age Factors↗

Effects of betaxolol on light responses and membrane conductance in retinal ganglion cells.

PURPOSE: To examine the physiological effects of betaxolol, a beta1-adrenergic receptor blocker commonly used in the treatment of glaucoma, on retinal ganglion cells and to evaluate its potential to elicit responses consistent with a neuroprotective agent against ganglion cell degeneration. METHODS: Single-unit extracellular recording, electroretinogram (ERG), intracellular and whole-cell patch-clamp recording techniques were made from flatmounted, isolated retina, superfused eyecup, and living retinal slice preparations of the larval tiger salamander. RESULTS: Bath application of 20 microM betaxolol reduced the glutamate-induced increase of spontaneous spike rate in retinal ganglion cell by approximately 30%. The glutamate-induced postsynaptic current recorded under voltage-clamp conditions was reduced by 50 microM betaxolol, and the difference current-voltage (I-V) relation (I(Control)-I(betaxolol)) was N-shaped and AP5-sensitive, characteristic of N-methyl-D-aspartate receptor-mediated current. Application of 50 microM betaxolol reversibly reduced the voltage-gated sodium and calcium currents by approximately one third of their peak amplitudes. The times-to-action of betaxolol on ganglion cells are long (15-35 minutes for 20-50 microM betaxolol), indicative of modulation through slow biochemical cascades. Betaxolol, up to 100 microM, exerted no effects on horizontal cells or the ERG, suggesting that the primary actions of this beta1 blocker are restricted to retinal ganglion cells. CONCLUSIONS: These physiological experiments provide supporting evidence that betaxolol acts in a manner consistent with preventing retinal ganglion cell death induced by elevated extracellular glutamate or by increased spontaneous spike rates under pathologic conditions. The physiological actions of betaxolol lead to reducing neurotoxic effects in ganglion cells, which are the most susceptible retinal neurons to glutamate-induced damages under ischemic and glaucomatous conditions. Therefore, betaxolol has the potential to be a neuroprotective agent against retinal degeneration in patients with disorders mediated by such mechanisms.

Adrenergic beta-Antagonists↗

BDNF enhances retinal ganglion cell survival in cats with optic nerve damage.

PURPOSE: To determine whether brain-derived neurotrophic factor (BDNF), a neuroprotectant in the small rat eye, might also serve as an effective neuroprotectant in larger vertebrate eyes. METHODS. A cat optic nerve crush model was combined with standard histologic staining and analysis techniques. Twenty-nine animals were studied, with the noninjected eye serving as the control eye. RESULTS: No treatment, or intravitreal injection of sterile water, resulted in an approximately 50% loss of ganglion cells 1 week after nerve crush. By contrast, the mean percentages of surviving ganglion cells measured in eyes receiving injections of 15, 30, 60, and 90 microg BDNF at the time of the nerve damage were 52%, 81%, 77%, and 70%, respectively. Similar values were obtained for ganglion cell density. Cell size measurements suggest a complex response among the different classes of cat ganglion cells; 30 microg BDNF treatment retained the highest number of large ganglion cells, whereas 90 microg minimized the loss of medium-sized neurons and retained normal proportions of large, medium, and small ganglion cells. CONCLUSIONS: The data show that BDNF is an effective neuroprotectant in primate-sized eyes after optic nerve injury. Although the amount required to achieve neuroprotection is much greater than that needed for the small rat eye (30 microg versus 0.5 microg), when differences in vitreal volume are considered, the effective dose is similar (0.01 microg BDNF/microl vitreal volume). High doses of BDNF induce inflammation and result in a decrease in total ganglion cell survival but appear necessary to save medium-sized neurons, which are affected most severely by nerve injury.

Animals↗

[Effects of low reactive level laser, linear polarized light and Xenon-ray irradiation on the stellate ganglion in dogs].

The aim of this study was to clarify the influence of low reactive level laser, linear polarized light and Xenon-ray irradiation on stellate ganglion activity in dogs. Under general anesthesia, the right stellate ganglion was exposed by thoracotomy. After stabilization of the hemodynamic parameters, the following baseline measurements were taken: mean arterial pressure (MAP), heart rate (HR), and right brachial artery blood flow (BABF). Experiment 1: The stellate ganglion was directly irradiated for 10 min with low reactive level laser, linear polarized light or Xenon-ray. The hemodynamic parameters were measured for 60 min after each irradiation. Immediately after the irradiation study, stellate ganglion blockade (SGB) with 0.5% mepivacaine 1.0 ml was performed. Experiment 2: After confirming a decrease in BABF by direct electrical stimulation on the stellate ganglion, the stellate ganglion was directly irradiated with low reactive level laser, linear polarized light or Xenon-ray. The hemodynamic parameters were measured for 60 min after each irradiation. Immediately after the irradiation study with 0.5% mepivacaine 1.0 ml was performed. The hemodynamic parameters were also measured for 60 min after SGB. The changes in variables were not statistically significant after each irradiation in the experiment 1 and 2. After SGB, a significant decrease in HR and a significant increase in BABF occurred in the experiment 1 and 2. In conclusion, this study demonstrated that irradiation with low reactive level laser, linear polarized light and Xenon-ray of the stellate ganglion did not induce sympathetic blockade in dogs.

Animals↗

[Study on voltage-sensitive current of spiral ganglion cells in mice organ of Corti culture].

OBJECTIVE: To investigate the property of voltage-sensitive current in cochlear spiral ganglion cells of the C57BL/10J mice, an inbred strain which develops early onset hearing loss. METHODS: Organotypic cultures of organ of Corti were prepared from neonatal mice 0-5 days of age. Whole-cell current and voltage clamp techniques were used to study Na+, K+ and Ca2+ currents of the spiral ganglion cells in culture. RESULTS: Cultures were maintained for 8-48 hours before use. Ganglion cells were identified first through their anatomical positions and finally through fast negative Na+ current. Spontaneous action potentials were recorded from some ganglion cells (4 out of 39). When present, spontaneous rates were around 20 spikes/sec, and might be as high as 135 spikes/sec. The mean resting potential was (-55 +/- 5) mV (n = 39). Under voltage clamp conditions, transient inward currents (negative) and outward (positive), steady-state voltage-dependent currents were recorded in normal HBSS. Rapid inward currents were totally blocked by 300 nM TTX applied locally to the culture. Inward currents recovered quickly after TTX wash out suggesting that the transient inward current was carried by Na+. The mean maximum amplitude of Na+ current was (-2.0 +/- 1.1) nA (n = 39) recorded in HBSS. Adding TEA (10 mmol/L) and 4-AP (0.15 mmol/L) to the bath solution or replacing K+ with Ca+ in the pipette solution partly blocked the sustained outward current. This suggests that the outward current was carried by K+. The mean maximum amplitude of K+ was (3.0 +/- 1.3) nA (n = 39) with 140 mM K+ in the pipette. Inward Ca2+ current was recorded in Ba2+ solution which mean peak amplitude was (-1.0 +/- 0.7) nA (n = 20). Ca2+ currents were reversibly blocked by 100 microM Cd2+. CONCLUSION: Whole cell recordings from spiral ganglion neurons can be obtained from organotypic cultures of the organ of Corti. Fast Na+ current, sustained K+ current and L-type Ca2+ current were recorded in the spiral ganglion cells cultured for 1-2 days. Whole cell recording showed that cochlea spiral ganglion cells can generate spontaneous action potential one day after birth and the firing rates could reach levels equal to those recorded in vivo.

Action Potentials↗

Inhibition of plasminogen activation protects against ganglion cell loss in a mouse model of retinal damage.

PURPOSE: The mechanisms that trigger ganglion cell death in ischemic retinal diseases are not clearly understood. Using a mouse optic nerve ligation model, the objective of this study was to test the hypothesis that extracellular matrix (ECM) modulating plasminogen activators (PAs) potentiate ganglion cell loss. METHODS: Optic nerve ligation was performed to initiate ganglion cell loss in the retina. Urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) activity in retinal extracts was determined by plasminogen/fibrinogen zymography. Immunostaining and western blot analysis was performed to detect uPA and tPA proteins. Plasmin activity was determined by casein gel-zymography. Plasminogen and plasmin proteins were detected and quantified by western blotting. Morphology was assessed using hematoxylin and eosin stained retinal cross sections, and programmed cell death was monitored by an apoptotic assay. Laminin degradation in retinal extracts was assessed by western blot analysis. RESULTS: Optic nerve ligation led to a transient increase in uPA and plasmin proteolytic activity in the retina. Urokinase inhibitor, amiloride, blocked uPA activity in retinal extracts. We found a correlation between the increased uPA activity, and conversion of zymogen plasminogen to active plasmin in retinal extracts with laminin degradation in the retina and apoptosis of ganglion cells. We found that by adding exogenous plasmin, in vitro, laminin present in control retinal extracts could be degraded in similar fashion. In addition, uPA or tPA failed to degrade laminin in control retinal extracts unless plasminogen was added, indicating that plasminogen activation is necessary for laminin degradation, in vitro. After intravitreal injection of plasmin inhibitor, alpha-2 antiplasmin, we found a significant protection against optic nerve ligation-induced ganglion cell loss. CONCLUSIONS: Optic nerve ligation-induced plasmin(ogen) activation that precedes ganglion cell loss suggest that specific targeting of plasmin activity may have therapeutic potential in preventing ganglion cell loss in retinal diseases.

Amiloride↗

The development of the spiral ganglion in the human foetus.

The development of the spiral ganglion was studied in steps sections of 81 human temporal bones. By the 8th week, the spiral ganglion has already separated from the vestibular ganglion. At 13 weeks two distinct populations are observed that correspond to neuron and Schwann cells. At 15 weeks the spiral ganglion has increased its distance from the cochlear duct and is surrounded by mesenchyme near the scala tympani. At 14 weeks a gradual decrease in the nucleus-to-cell area ratio was observed in spiral ganglion neurons that may reflect a morphological adaptation to function. By the 23rd week the modiolus begins to ossify and the spiral ganglion is surrounded by bony trabeculae. The time course of spiral ganglion development follows that of the stria vascularis and organ of Corti, although maturation changes are still observed in the neuronal population even beyond 20 weeks.

Cell Nucleus↗

Specific routing of retinal ganglion cell axons at the mammalian optic chiasm during embryonic development.

During development of the mammalian CNS, axons encounter multiple pathway choices on their way to central target structures. A major pathway branch point in the visual system occurs at the optic chiasm, where retinal ganglion cell axons may either enter the ipsilateral or the contralateral optic tract. To investigate whether embryonic mouse retinal ganglion cell axons, upon reaching the optic chiasm, selectively grow into the correct pathway, developing retinal ganglion cells were retrogradely labeled using either 1,1'-dioctadecyl- 3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) or fluorescent microspheres placed into the optic tract on one side. The distribution of ipsilaterally and contralaterally projecting ganglion cells in the embryo was then examined and compared to that of the adult animal. Results show that axon routing at the chiasm is already extremely adult-like as early as embryonic day 15 (E15), shortly after retinal axons arrive at the chiasm. [Retinal ganglion cell neurogenesis = E11-E18 (Drager, 1985); birth = E21.] Throughout the development of this pathway, routing errors are infrequent and are on the order of only about 3-8/1000 retinal ganglion cells. Thus, embryonic retinal ganglion cell axons do not project randomly at the optic chiasm but instead appear to be highly specific in their choice of pathway. To learn how correct pathway choices are made, retinal axons were retrogradely labeled with Dil and their trajectories at the optic chiasm were reconstructed. Results show that ipsilaterally and contralaterally projecting axons are highly intermixed as they enter the chiasm region but selectively grow into the correct pathway. For example, a contralaterally projecting axon near the entrance of the ipsilateral optic tract will turn and bypass this pathway and grow towards the midline to head into the contralateral optic tract. Similarly, axons far away from the ipsilateral optic tract frequently turn abruptly at right angles to enter the ipsilateral tract, directly crossing over contralaterally projecting axons heading to the opposite side. The sorting out of intermixed ipsilaterally and contralaterally projecting retinal axons into the appropriate optic tracts strongly suggests the presence of specific guidance cues at the optic chiasm during embryonic development. Together, results from this study demonstrate that the pattern of axon projection at the adult mammalian optic chiasm is gradually built upon a highly specific pattern of axon routing laid down early during development.

Animals↗

Class-specific cell death shapes the distribution and pattern of central projection of cat retinal ganglion cells.

The development of the nasotemporal division in cat retina was studied. We find that in the normally pigmented neonatal cat significant numbers of ganglion cells of all types in temporal retina project to the contralateral dorsal lateral geniculate nucleus (LGNd); far fewer cells in temporal retina project contralaterally to the LGNd in the normal adult. Thus, most of these cells must be eliminated during development. Experimental interruption of one optic tract in the neonate results in the retrograde degeneration of the ipsilaterally projecting ganglion cells in the temporal retina ipsilateral to the lesion. Consequent to the loss of the ipsilaterally projecting cells in this hemiretina, many of the ganglion cells projecting to the intact contralateral LGNd, which are normally eliminated, survive. Also, unlike in the normal cat, in which very few of the small ganglion cells in temporal retina project contralaterally to the thalamus, in optic tract sectioned (OTX) cats, significant numbers of the smallest ganglion cells in the temporal retina ipsilateral to the lesion project contralaterally to the intact thalamus. In order to make a quantitative comparison of the distributions of ipsilaterally and contralaterally projecting cells in the temporal retinae of normal cats, OTX cats, and neonatal kittens, it was necessary to determine the position of the vertical meridian in all animals. We defined the vertical meridian as the median edge (Stone, 1966). The median edge was determined from the distribution of the most nasally located, ipsilaterally projecting cells in temporal retina. The results indicate that the angle of the vertical meridian (median edge) with respect to the area centralis and optic disc is specified before birth and does not differ in normal cats, OTX cats, or neonatal kittens. Since the location of the vertical meridian does not change with age in postnatal life and is not affected by optic tract section, corresponding regions of retina in the different groups could be compared. A quantitative analysis of ganglion cell density in the temporal retina contralateral to the section, ipsilateral to the intact hemisphere, indicated that there was a reduction in the population of ipsilaterally projecting ganglion cells that was complementary to the abnormally large number of contralaterally projecting cells surviving in the temporal retina ipsilateral to the lesion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Selective loss of retinal ganglion cells in albino avian glaucoma.

Retinal ganglion cell loss was investigated in the retinae of albino quails before and after the development of glaucoma. The isodensity maps of ganglion cells, the total number of ganglion cells, and the histograms of the cell size in the central region of the retina were similar between albino quails without glaucoma and pigmented quails. However, ganglion cells in the intermediate and peripheral regions of the albino quails retina without glaucoma were significantly smaller than those of the pigmented quail retina. In albino quails with moderate glaucoma in 3 months of age, 11% to 55% of all the retinal ganglion cells had disappeared, with the loss of medium-sized cells (30-60 micron2 occurring earlier than that of small and large cells. In albino quails with advanced glaucoma, there was marked cupping around the optic nerve head, and only small ganglion cells remained in the ganglion cell layer.

Albinism↗

[The spiral ganglion of the rhesus monkey].

Four temporal bones of rhesus monkeys were investigated in respect of composition and morphology of the spiral ganglion cells. Using light and electron microscopic technique two main types of ganglion cells could be distinguished, namely 90% large (type I) and 10% small (type II) cells. Both small and large ganglion cells are surrounded by myelin sheaths: 90% of the large neurons are surrounded by myelin sheaths, whereas only 15% of the small neurons have a myelin sheath. The small neurons are exclusively connected with unmyelinated nerve-endings forming synaptic contact with the cell surface. These nerve endings contain vesicles similar to synaptic vesicles; the cytoplasm of the adjacent small ganglion cells contains dense core vesicles. Similar dense core vesicles are, however, also found in the cytoplasm of the large ganglion cells and in the axoplasm of the corresponding nerve axons. It is only in the cytoplasm of the small ganglion cells that dense bundles of neurofilaments are present. It seems that the nerve endings resembling synapses and contacting the small ganglion cells belong to the efferent, olivo-cochlear spiral bundle.

Animals↗

Structure and function of retinal ganglion cells innervating the cat's geniculate wing: an in vitro study.

We have examined in vitro the morphology and visual response properties of retinal ganglion cells innervating a component of the cat's lateral geniculate nucleus known as the geniculate wing (or retinorecipient zone of the pulvinar). Ganglion cells were first labeled in situ by retrograde transport of fluorescent microspheres from the geniculate wing. Labeled cells were injected intracellular with Lucifer yellow and biocytin in the isolated retina and visualized immunohistochemically. With one exception, stained cells appeared to belong to a single morphological class that corresponded closely to the epsilon cell of earlier descriptions (Leventhal et al., 1980; Rodieck and Watanabe, 1986). They had somas comparable in size to those of beta cells and large, sparse dendritic trees that ramified in the inner (ON) sublayer of the inner plexiform layer. Dendritic fields increased in size with eccentricity, but only within the central retina, and were among the largest so far reported for cat ganglion cells, exceeding those of alpha cells at most eccentricities. Dendritic profiles were typically elliptical with long axes pointing toward the area centralis. Axons were about as thick as those of beta cells and thicker than those of other varieties of non-alpha, non-beta ganglion cells. We recorded extracellularly from microsphere-labeled wing-projecting ganglion cells in a superfused, flattened eyecup preparation. All such cells exhibited sustained responses to standing contrast and had very large, concentric receptive fields with ON-centers and OFF-surrounds. Their response to gratings showed that they have relatively poor spatial resolution and a moderate amount of nonlinearity of spatial summation. These cells thus have many physiological response properties in common with ganglion cells previously termed "on-center tonic W-cells," "on-center sluggish sustained cells," and "Q-cells." These findings indicate that ganglion cells innervating the cat's geniculate wing form a structurally and functionally homogeneous class. Their large dendritic and receptive fields and low-pass spatial frequency tuning suggest that fine spatial resolution is not required for the execution of their functional role(s).

Animals↗

Fetal NGF augmentation preserves excess trigeminal ganglion cells and interrupts whisker-related pattern formation.

In the developing nervous system, precisely patterned connections result from mechanisms that remodel initially diffuse connections. For example, ocular dominance column formation depends upon activity-based competitive interactions. In the developing trigeminal (V) somatosensory system, injury to afferent inputs prevents somatotopic pattern formation; however, afferent impulse blockade does not. What establishes central V patterns remains unclear. As a first step in assessing the role of neurotrophins in naturally occurring death of V ganglion cells and whisker-related pattern formation, the consequences of prenatal NGF injections were evaluated. Fetal rats given NGF on both embryonic day (E) 15 and E18 had 36% more V ganglion cells than normal and lacked whisker-related patterns in the V brainstem complex at birth and through postnatal day 3, as determined by cytochrome oxidase histochemistry. Rats injected with NGF on E16 or on E18, or with vehicle had normal ganglion cell numbers and brainstem patterns. Animals injected with antibodies to NGF or an NGF receptor had reduced ganglion cell numbers and normal brainstem patterns. These findings suggest that naturally occurring cell death in the V ganglion is neurotrophically regulated and that this process impacts upon somatotopic pattern formation in the V brainstem complex. Results of anterograde tracing experiments in NGF-augmented animals suggest that pattern disruptions are due to an absence of whisker-related patterning in the central projections of V ganglion cells. Moreover, single primary afferent collaterals labeled by Neurobiotin injections in the V ganglion did not have widespread or unusually complex arbors. Thus, NGF may affect V pattern formation by preserving or inducing projections to brainstem regions that normally come to lack such projections, such as the spaces normally demarcating neighboring whisker primary afferent projections.

Animals↗

The M-ganglion cell density gradient in New World monkeys.

The M-ganglion cell distribution was studied in the retinae of New World monkeys, the diurnal Cebus and the nocturnal Aotus. Retinal whole mounts were stained by the neurofibrillar method of Gros-Schultze. The M-ganglion cell distribution in the Cebus and Aotus is similar to that reported for Old World primates, such as the Macaca. The M-ganglion cell density peak occurs in the foveal slope and declines towards the periphery. There is a nasotemporal asymmetry: in the Cebus retina the M-ganglion cell density is 1.2-4.3 times higher in the nasal when compared to the temporal region at the equivalent eccentricities; in the Aotus, the nasotemporal asymmetry is smaller, 1.6-2.2 higher in the nasal region. We compared the M-ganglion cell density with previously published values for the density of the total population of ganglion cells and observed a larger proportion of M-ganglion cells in the Aotus, when compared with Cebus or Macaca.

Animals↗