Threshold setting by the surround of cat retinal ganglion cells

1. The slope of curves relating the log increment threshold to log background luminance in cat retinal ganglion cells is affected by the area and duration of the test stimulus, as it is in human pyschophysical experiments. 2. Using large area, long duration stimuli the slopes average 0-82 and approach close to 1 (Weber's Law) in the steepest cases. Small stimuli gave an average of 0-53 for on-centre units using brief stimuli, and 0-56 for off-centre units, using long stimuli. Slopes under 0-5 (square root law) were not found over an extended range of luminances. 3. On individual units the slope was generally greater for larger and longer test stimulus, but no unit showed the full extent of change from slope of 0-5 to slope of 1. 4. The above differences hold for objective measures of quantum/spike ratio, as well as for thresholds either judged by ear or assessed by calculation. 5. The steeper slope of the curves for large area, long duration test stimuli compared with small, long duration stimuli, is associated with the increased effectiveness of antagonism from the surround at high backgrounds. This change may be less pronounced in off-centre units, one of which (probably transient Y-type) showed no difference of slope, and gave parallel area-threshold curves at widely separated background luminances, confirming the importance of differential surround effectiveness in changing the slope of the curves. 6. In on-centre units, the increased relative effectiveness of the surround is associated with the part of the raised background light that falls on the receptive field centre. 7. It is suggested that the variable surround functions as a zero-offset control that sets the threshold excitation required for generating impulses, and that this is separate from gain-setting adaptive mechanisms. This may be how ganglion cells maintain high incremental sensitivity in spite of a strong maintained excitatory drive that would otherwise cause compressive response non-linearities.     

Tritiated uridine uptake in the retinal ganglion cell layer of the cat during normal development and after visual cortex ablation

The short-term metabolic response of immature retinal ganglion cells to destruction of their target cells in the dorsal lateral geniculate nucleus (dLGN) was assessed in newborn cats. Retrograde degeneration of virtually all dLGN cells was induced by ablation of the 13 contiguous areas of visual cortex on the day of birth. The metabolic response of retinal ganglion cells to this loss of target cells in dLGN was determined by exposing the ganglion cell layer to tritiated uridine, a precursor of RNA. Control measurements were made from unoperated littermates. Following sectioning and processing of the retinae from both groups of kittens for autoradiography, silver grain densities overlying the cellular profiles in the ganglion cell layer were calculated. These calculations revealed levels of uridine incorporation at Postnatal Day 4 in both groups of kittens significantly higher than at either Postnatal Day 2 or 7, but no significant differences between the two groups on any day examined. These results show that the level of RNA synthesis in retinal ganglion cells increases temporarily during the first postnatal week and that this synthesis is unaffected by the death of target cells in the dLGN. The temporary increase may be related to the establishment of synaptic connections on retinal ganglion cells by their afferent bipolar and amacrine neurons in the inner nuclear layer.     

Activation and inactivation properties of voltage-gated calcium currents in developing cat retinal ganglion cells

The correlated activity of developing retinal ganglion cells is essential for the reorganization and refinement of retinogeniculate projections. Previous studies have uncovered marked changes in the spiking properties of retinal ganglion cells during this period of reorganization; however, a full understanding of the changes in the underlying ionic conductances has yet to be obtained. To this end, the whole-cell configuration of the patch-clamp technique was used to record currents conducted by voltage-gated calcium channels in 83 dissociated cat retinal ganglion cells obtained from animals aged between embryonic day 34 and postnatal day 105. Calcium currents, magnified by using barium as the major charge carrier, were isolated by substituting choline for Na+ in the bathing solution and Cs+ for K+ in the electrode solution. Three voltage-gated Ca2+ conductances were identified based on their voltage dependence and kinetics of activation and inactivation: a transient low-voltage-activated conductance, a transient high-voltage-activated conductance and a sustained high-voltage-activated conductance. During the developmental period examined there were significant increases in the densities of all three conductances, as well as significant changes in some of their activation and inactivation properties. These findings, together with those reported previously for the voltage-gated Na+ and K+ conductances, are related to the generation of excitability in developing retinal ganglion cells during a period critical to the normal development of the visual system. Furthermore, while the sustained high-voltage-activated conductance was present in all of the retinal ganglion cells observed, only about 72% expressed the transient high-voltage-activated current. During the developmental period examined, there was also an increase in the proportion of cells expressing the transient low-voltage-activated conductance. This, along with our previous finding that retinal ganglion cells heterogeneously express different types of voltage-gated K+ channels, strongly suggests that the spiking patterns observed in different classes of retinal ganglion cell may be due, in part, to their intrinsic membrane properties.     

Effects of GDNF on retinal ganglion cell survival following axotomy

Recent evidence suggests that approximately 90% of retinal ganglion cells (RGCs) die by the process of apoptosis within 14 days of optic nerve transection. RGCs begin to disappear from the retina between 5 and 7 days postaxotomy when the highest percentage of RGCs show characteristics typical of apoptosis. A single intraocular injection of glial cell-line derived neurotrophic factor (GDNF) given at the time of axotomy resulted in a delay in the initiation of RGC death and increased the densities of surviving RGCs at 7, 10 and 14 days postaxotomy. The mean RGC densities in GDNF treated retinas at 7 (2381 +/- 144), 10 (1561 +/- 117) and 14 (1123 +/- 116) days postaxotomy were significantly higher than that of controls (1835 +/- 82, 835 +/- 272 and 485 +/- 39, respectively). The loss of RGCs was paralleled by increases in TUNEL positive staining in control retinas and a lower percentage of TUNEL positive cells in GDNF treated retinas at 5, 7 and 10 days postaxotomy. These results suggest that GDNF is capable of promoting RGC survival following injury, possibly by interfering with an essential step in apoptosis.     

Age-dependent and cell class-specific modulation of retinal ganglion cell bursting activity by GABA

Competition for postsynaptic targets during development is thought to be driven by differences in temporal patterns of neuronal activity. In the ferret visual system, retinal ganglion cells that are responsive either to the onset (On) or to the offset (Off) of light exhibit similar patterns of spontaneous bursting activity early in development but later develop different bursting rhythms during the period when their axonal arbors segregate to occupy spatially distinct regions in the dorsal lateral geniculate nucleus. Here, we demonstrate that GABAergic transmission plays an important, although not exclusive, role in regulating the bursting patterns of morphologically identified On and Off ganglion cells. During the first and second postnatal weeks, blocking GABAA receptors leads to a decrease in the bursting activity of all ganglion cells, suggesting that GABA potentiates activity at the early ages. Subsequently, during the period of On-Off segregation in the geniculate nucleus, GABA suppresses ganglion cell bursting activity. In particular, On ganglion cells show significantly higher bursting rates when GABAergic transmission is blocked, but the bursting rates of Off ganglion cells are not affected systematically. Thus, developmental differences in the bursting rates of On and Off ganglion cells emerge as GABA becomes inhibitory and as it consistently and more strongly inhibits On compared with Off ganglion cells. Because in many parts of the CNS GABAergic circuits appear early in development, our results also implicate a potentially important and possibly general role for local inhibitory interneurons in creating distinct temporal patterns of presynaptic activity that are specific to each developmental period.     

Conductances evoked by light in the ON-beta ganglion cell of cat retina

We have addressed the role of Ca2+ channels in mossy fiber synaptic transmission and long-term potentiation (LTP). Whereas the induction of mossy fiber LTP is entirely normal when synaptic transmission is blocked by the glutamate receptor antagonist kynurenate, LTP is blocked in the absence of extracellular Ca2+. These findings suggest that presynaptic Ca2+ entry is essential for mossy fiber LTP. Therefore, the role of different types of presynaptic Ca2+ channels in synaptic transmission and LTP was investigated. Mossy fiber responses were little affected by the L-type Ca2+ channel blocker nifedipine. They were blocked partially by omega-conotoxin-GVIA (N-type) and almost entirely by omega-agatoxin-IVA (P-type). None of these antagonists blocked mossy fiber LTP, nor was its expression associated with a change in sensitivity of synaptic transmission to either of the two toxins. These results, together with previous findings, suggest that the induction of mossy fiber LTP is critically dependent on the entry of Ca2+ into the presynaptic terminal to trigger a series of steps resulting in the long lasting enhancement of evoked glutamate release. Whereas P-type Ca2+ channels are of primary importance in mossy fiber synaptic transmission, both the induction and expression of mossy fiber LTP can occur in the absence of P-type (or N-type) Ca2+ channels.     

Dendritic field development of retinal ganglion cells in the cat following neonatal damage to visual cortex: evidence for cell class specific interactions

A well-known feature of the mammalian retina is the inverse relation that exists in central and peripheral retina between the density of retinal ganglion cells and their dendritic field sizes. Functionally, this inverse relation is thought to represent a means by which retinal coverage is maintained, despite significant changes in ganglion cell density. While it is generally agreed that the dendritic fields of mature retinal ganglion cells reflect, in part, competitive interactions that occur during development, the issue of whether these interactions are cell class specific remains unclear. In order to examine this question, we used intracellular staining techniques and an in vitro, living retina preparation to compare the soma and dendritic field sizes of alpha and beta ganglion cells from normal retinae with those of cells located in matched areas of retinae in which the density of beta ganglion cells had been reduced selectively by neonatal removal of visual cortex areas 17, 18, and 19. Our intracellular data show that while an early, selective, reduction in beta cell density has little or no effect on the cell body and dendritic field sizes of mature alpha cells, it results in a 13% increase in the mean soma area and an 83% increase in the mean dendritic field area of surviving beta cells. This differential effect suggests that the soma and dendritic field sizes of alpha and beta ganglion cells in the mature cat retina result primarily from competitive interactions during development that are cell class specific.     

Cross-species collapse activity of polarized radial glia on retinal ganglion cell axons

Anxiety sensitivity has been implicated as a risk factor in the development and maintenance of anxiety and fear-related disorders. Indeed, persons who score high on the anxiety sensitivity index (ASI) are generally more responsive to biological challenge procedures such as CO2-inhalation that directly evoke the feared bodily events. One would expect, therefore, that persons high on anxiety sensitivity should be more conditionable and hence more likely to acquire fears, than persons low on anxiety sensitivity when CO2-enriched air is used as an unconditioned stimulus (UCS). Undergraduates (N = 96), scoring high, medium and low on the ASI received 8 repeated 20-s inhalations of either 20 or 13% CO2-enriched air (UCSs) paired with one of three CSs differing in fear-relevance (snake, heart and flowers). Several autonomic and self-report measures were assessed. Contrary to expectation, electrodermal and cardiac conditioned responses failed to discriminate between ASI groups. Yet, SUDS and severity and frequency of DSM-IV panic symptoms varied reliably as a function of anxiety sensitivity. Overall, the findings suggest that anxiety sensitivity is related to subjective fear-related complaints, but not autonomic responding and conditionability. We discuss clinical and theoretical implications for understanding the place fo anxiety sensitivity in fear onset.     

Axonal regeneration of retinal ganglion cells

We have developed retinal culture system of adult mammals to investigate neural regeneration from adult retinal ganglion cells (RGC). In this culture system, neurites were regenerated from RGCs of adult retinal explants. Investigation of neurotrophic effects on the neural regeneration showed that some interleukins and neurotrophins enhanced neurite regeneration from adult rat RGCs. We also found that the adult human retina had the ability of neural regeneration and that neurotrophins enhanced this ability. A novel neurotrophic factor secreted by adult rat hepatocytes also enhanced neurite regeneration not only in adult mice but also in aged RGCs. This result indicated the novel hepatocyte secreted factor is an activator which enhances neural regeneration of the aged retina. We concluded that even adult aged RGCs had the ability of axonal regeneration after injury and that neurotrophic factors might enhanced these abilities. Therefore neurotrophic factors might have practicable applications in drug treatments for intractable disease of the neural retina and optic nerve. Future progress of neuroscience is expected to rescue the retina from various diseases, and to render possible the transplantation of the retina and optic nerve.     

Synaptology of physiologically identified ganglion cells in the cat retina: a comparison of retinal X- and Y-cells

It has long been known that a number of functionally different types of ganglion cells exist in the cat retina, and that each responds differently to visual stimulation. To determine whether the characteristic response properties of different retinal ganglion cell types might reflect differences in the number and distribution of their bipolar and amacrine cell inputs, we compared the percentages and distributions of the synaptic inputs from bipolar and amacrine cells to the entire dendritic arbors of physiologically characterized retinal X- and Y-cells. Sixty-two percent of the synaptic input to the Y-cell was from amacrine cell terminals, while the X-cells received approximately equal amounts of input from amacrine and bipolar cells. We found no significant difference in the distributions of bipolar or amacrine cell inputs to X- and Y-cells, or ON-center and OFF-center cells, either as a function of dendritic branch order or distance from the origin of the dendritic arbor. While, on the basis of these data, we cannot exclude the possibility that the difference in the proportion of bipolar and amacrine cell input contributes to the functional differences between X- and Y-cells, the magnitude of this difference, and the similarity in the distributions of the input from the two afferent cell types, suggest that mechanisms other than a simple predominance of input from amacrine or bipolar cells underlie the differences in their response properties. More likely, perhaps, is that the specific response features of X- and Y-cells originate in differences in the visual responses of the bipolar and amacrine cells that provide their input, or in the complex synaptic arrangements found among amacrine and bipolar cell terminals and the dendrites of specific types of retinal ganglion cells.     

Delay of ganglion cell death by tetrodotoxin during retinal development in chick embryos

Acid-soluble collagen from rat skin was modified by active oxygen in vitro, and properties of the modified collagen as a substratum for fibroblasts were studied. When collagen was treated with ascorbate-copper ion systems, cross-linking and a little degradation occurred rapidly. The cells attached but spread poorly on the modified collagen gel as compared with on the untreated collagen gel. On the other hand, when collagen was treated with H2O2-copper ion systems, only degradation of collagen molecule occurred rapidly. This treatment did not affect the attachment and spreading of the cells on the collagen gel, but when the incubation was continued for a long time, the cells migrated actively and gathered. Thymidine incorporation by the cells was suppressed on both modified collagen gels as compared with that on untreated collagen gel, and the extent of the suppression on the H2O2-copper-treated collagen was larger than that on the ascorbate-copper-treated collagen. These results indicate that the active oxygen-induced cross-linking and degradation significantly alter properties of collagen as a substratum for fibroblasts.     

Interactions of inhibition and excitation in the light-evoked currents of X type retinal ganglion cells

The excitatory and inhibitory conductances driving the light-evoked currents (LECs) of cat and ferret ON- and OFF-center X ganglion cells were examined in sliced and isolated retina preparations using center spot stimulation in tetrodotoxin (TTX)-containing Ringer. ON-center X ganglion cells showed an increase in an excitatory conductance reversed positive to +20 mV during the spot stimulus. At spot offset, a transient inhibitory conductance was activated on many cells that reversed near ECl. OFF-center X ganglion cells showed increases in a sustained inhibitory conductance that reversed near ECl during spot stimulation. At spot offset, an excitatory conductance was activated that reversed positive to +20 mV. The light-evoked current kinetics of ON- and OFF-center X cells to spot stimulation did not significantly differ in form from their Y cell counterparts in TTX Ringer. When inhibition was blocked, current-voltage relations of the light-evoked excitatory postsynaptic currents (EPSCs) of both ON- and OFF-X cells were L-shaped and reversed near 0 mV. The EPSCs averaged between 300 and 500 pA at -80 mV. The metabotropic glutamate receptor agonist 2-amino-4-phosphonobutyric acid (APB), was used to block ON-center bipolar cell function. The LECs of ON-X ganglion cells were totally blocked in APB at all holding potentials. APB caused prominent reductions in the dark holding current and synaptic noise of ON-X cells. In contrast, the LECs of OFF-X ganglion cells remained in APB. An increase in the dark holding current was observed. The excitatory amino acid receptor antagonist combination of D-amino-5-phosphono-pentanoic acid (D-AP5) and 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo-(F)-quinoxalinedione (NBQX) was used to block ionotropic glutamate receptor retinal neurotransmission. The LECs of all ON-X ganglion cells were totally blocked, and their holding currents were reduced similar to the actions of APB. For OFF-X ganglion cells, the antagonist combination always blocked the excitatory current at light-OFF; however, in many cells, the inhibitory current at light-ON remained. ON-center X ganglion cells receive active excitation during center illumination, and a transient inhibition at light-OFF. In contrast OFF-center X ganglion cells experience a sustained active inhibition during center illumination, and a shorter increase in excitation at light-offset. Cone bipolar cells provide a resting level of glutamate release on X ganglion cells on which their light-evoked currents are superimposed [corrected].     

Response of retinal ganglion cell axons to striped linear gradients of repellent guidance molecules

The application of molecular biology in the study of the pathogenesis of herpes simplex virus type 1 (HSV-1) has led to significant advances in our understanding of mechanisms that regulate virus behavior in sensory neurons and epithelial tissue. Such study has provided insight into the relationship of host and viral factors that regulate latency, reactivation, and recurrent disease. This review attempts to distill decades of information involving human, animal, and cell culture studies of HSV-1 with the goal of correlating molecular events with the clinical and laboratory behavior of the virus during latency, reactivation, and recurrent disease. The purpose of such an attempt is to acquaint the clinician/scientist with the current thinking in the field, and to provide key references upon which current opinions rest.     

Requirement for Brn-3b in early differentiation of postmitotic retinal ganglion cell precursors

Postnatal development of the spinal cord serotonergic (5-HT) system and of swimming movements were studied in newborn Sprague-Dawley rats, in which the serotonin level in the central nervous system was lowered in the prenatal period. For this purpose, para-chlorophenylalanine (PCPA) (300 mg/kg) was administered intraperitoneally to pregnant mother rats on day 8 of gestation, followed by a daily injection of PCPA (80 mg/kg) from day 9 of gestation to delivery. The postnatal development of the 5-HT system in the spinal cord of the pups (PCPA-treated pups) born from the PCPA-administered mothers was markedly delayed during the period between PND 1 and PND 10 in comparison to that in the control pups born from healthy mothers. Postnatally, the control pups developed their swimming movements regularly through three distinct phases: forelimb dominant, forelimb and hindlimb well coordinated, hindlimb dominant. In contrast, in the PCPA-treated pups, swimming movements were disorganized during the period in which the development of 5-HT system was delayed. However, between PND 17 and 22 in which the 5-HT system developed to that extent observed in the control pups, the pups eventually developed swimming movements as observed in the control pups. These results suggest that the disorganized developmental process of swimming movements in the PCPA-treated pups is due to the possible failure in the prenatal and postnatal development of the 5-HT system and its target system in the brain stem and the spinal cord.     

Eph receptor-ligand interactions are necessary for guidance of retinal ganglion cell axons in vitro

Previous results of an in vitro guidance test, the stripe assay, have demonstrated the presence of a repulsive axon guidance activity for temporal retinal axons in the posterior part of the vertebrate optic tectum. Ephrin-A5 and Ephrin-A2 are ligands for the EphA subfamily of Eph receptor tyrosine kinases, which are expressed in overlapping gradients in the posterior part of the tectum. When recombinantly expressed, both proteins have been shown to guide retinal ganglion cell axons in the stripe assay. While these results suggest that Ephrin-A5 and Ephrin-A2 form part of the posterior repulsive guidance activity, they do not elucidate whether they are necessary components. Here we report that soluble forms of the ligands at nanomolar concentrations completely abolish this repulsive activity. Similar results were obtained with the soluble extracellular domain of EphA3, which is a receptor for Ephrin-A2 and Ephrin-A5, but not with the corresponding domain of EphB3, a receptor for the transmembrane class of Eph ligands. These experiments show that the repulsive axon guidance activity seen in the stripe assay is mediated by Ephrin-A ligands.     

Acquired retinal folds in the cat

Retinal folds were found in 5 cats. The apparent cause of the folding was varied: in 1 cat the folds appeared after a localized retinal detachment; in 2 cats the condition accompanied other intraocular abnormalities associated with feline infectious peritonitis; 1 cat had active keratitis, and the retinal changes were thought to have been injury related; and 1 cat, bilaterally affected, had chronic glomerulonephritis.     

The receptive field of the primate P retinal ganglion cell, II: Nonlinear dynamics

The ganglion cells of the primate retina include two major anatomical and functional classes: P cells which project to the four parvocellular layers of the lateral geniculate nucleus (LGN), and M cells which project to the two magnocellular layers. The characteristics of the P-cell receptive field are central to understanding early form and color vision processing (Kaplan et al., 1990; Schiller & Logothetis, 1990). In this and in the following paper, P-cell dynamics are systematically analyzed in terms of linear and nonlinear response properties. Stimuli that favor either the center or the surround of the receptive field were produced on a CRT and modulated with a broadband signal composed of multiple m-sequences (Benardete et al., 1992b; Benardete & Victor, 1994). The first-order responses were calculated and analyzed in this paper (part I). The findings are: (1) The first-order responses of the center and surround depend linearly on contrast. (2) The dynamics of the center and surround are well described by a bandpass filter model. The most significant difference between center and surround dynamics is a delay of approximately 8 ms in the surround response. (3) In the LGN, these responses are attenuated and delayed by an additional 1-5 ms. (4) The spatial transfer function of the P cell in response to drifting sine gratings at three temporal frequencies was measured. This independent method confirmed the delay between the (first-order) responses of the center and surround. This delay accounts for the dependence of the spatial transfer function on the frequency of stimulation.