Dendritic co-stratification of ON and ON-OFF directionally selective ganglion cells with starburst amacrine cells in rabbit retina.

The morphology, dendritic branching patterns, and dendritic stratification of retinal ganglion cells have been studied in Golgi-impregnated, whole-mount preparations of rabbit retina. Among a large number of morphological types identified, two have been found that correspond to the morphology of ON and ON-OFF directionally selective (DS) ganglion cells identified in other studies. These cells have been characterized in the preceding paper in terms of their cell body size, dendritic field size, and branching pattern. In this paper, the two kinds of DS ganglion cell are compared in terms of their levels of dendritic stratification. They are compared with each other and also with examples of class III.1 cells, defined in the preceding paper with reference to our previous studies. Studies employing computer-aided, 3D reconstruction of dendritic trees, as well as analysis of a pair of ON DS and ON-OFF DS ganglion cells with overlapping dendritic trees show that the two types of DS ganglion cell partly co-stratify in the middle of sublamina b (stratum 4). The report that some ON DS ganglion cells extend a few dendrites into sublamina a is confirmed. The study of pairs of ON-OFF DS ganglion cells and starburst amacrine cells with overlapping dendritic trees reveals a precise co-stratification of these two cell types, and many points of close apposition of starburst boutons with ON-OFF DS ganglion cell dendrites in both sublaminae of the inner plexiform layer (IPL). This is confirmed by high-resolution light microscopy and by electron microscopy. It is possible to conclude, therefore, that ON DS are also partly co-stratified with type b starburst (cholinergic) amacrine cells, and are apparently also partly co-stratified with type a starburst amacrine cells, when occasional dendrites rise to that level. The co-stratification of the two kinds of DS ganglion cell is consistent with the sharing of some inputs in common, including some cone bipolar cell inputs. The co-stratification of both with starburst amacrine cells agrees with the physiological demonstration of the powerful pharmacological effects upon ON and ON-OFF DS ganglion cells reported for cholinergic agonists. The major difference in the dendritic stratification of bistratified ON-OFF DS ganglion cells and generally unistratified ON DS ganglion cells is consistent with the bisublaminar organization of ON and OFF pathways in the IPL. The problem of occasional branches of ON DS cells in sublamina a is discussed in terms of a threshold for OFF responses.(ABSTRACT TRUNCATED AT 400 WORDS)     

Selective abolition of OFF responses in kainic acid-lesioned chicken retina

When ganglion cell responses were recorded from optic axons in the superficial layers of the chicken optic tectum, the responses recorded are predominantly ON-OFF transient, with some ON transient, and rare OFF transient responses. Several weeks after excitotoxic lesion of the retina with 40 nmol of kainic acid injected intravitreally, only ON transient responses could be recorded from the contralateral optic tectum. ON response latency and threshold were not affected. At low light intensities responses in the kainic acid-lesioned retinas showed a sustained component which was not detected in control retinas, but at high light intensities, the sustained component disappeared and the responses were extremely transient. The disappearance of the OFF responses seems to be due to elimination of the OFF component of the responses of cells which are normally ON-OFF transient, rather than the silencing of these cells, leaving only the normally ON transient cells. Morphological evidence suggests that approximately two thirds of the bipolar cells and most amacrine cells are destroyed by the kainic acid lesion (Ingham and Morgan, Neuroscience, 9 (1983) 165-181), and pharmacological logic (Morgan, Prog. Retinal Res., 2 (1983) 247-266) suggests that the missing bipolar cells should be OFF bipolar cells. These results therefore suggest that ON-OFF transient cells receive direct input from bipolar cells, which determines their basic response type. These results also suggest that amacrine cells have little if any role to play in the generation of the basic centre responses of these ON-OFF transient ganglion cells, and that while amacrine cells may have a role in the generation of transient responses in the inner plexiform layer, transient responses can be generated without the intervention of amacrine cells, particularly at high intensities.     

Light-evoked synaptic activity of retinal ganglion and amacrine cells is regulated in developing mouse retina

Recent studies have shown a continued maturation of visual responsiveness and synaptic activity of retina after eye opening, including the size of receptive fields of retinal ganglion cells (RGCs), light-evoked synaptic output of RGCs, bipolar cell spontaneous synaptic inputs to RGCs, and the synaptic connections between RGCs and ON and OFF bipolar cells. Light deprivation retarded some of these age-dependent changes. However, many other functional and morphological features of RGCs are not sensitive to visual experience. To determine whether light-evoked synaptic responses of RGCs undergo developmental change, we directly examined the light-evoked synaptic inputs from ON and OFF synaptic pathways to RGCs in developing retinas, and found that both light-evoked excitatory and inhibitory synaptic currents decreased, but not increased, with age. We also examined the light-evoked synaptic inputs from ON and OFF synaptic pathways to amacrine cells in developing retinas and found that the light-evoked synaptic input of amacrine cells is also downregulated in developing mouse retina. Different from the developmental changes of RGC spontaneous synaptic activity, dark rearing has little effect on the developmental changes of light-evoked synaptic activity of both RGCs and amacrine cells. Therefore, we concluded that the synaptic mechanisms mediating spontaneous and light-evoked synaptic activity of RGCs and amacrine cells are likely to be different.     

Regulation of neonatal development of retinal ganglion cell dendrites by neurotrophin‐3 overexpression

The morphology of dendrites constrains and reflects the nature of synaptic inputs to neurons. The visual system has served as a useful model to show how visual function is determined by the arborization patterns of neuronal processes. In retina, light ON and light OFF responding ganglion cells selectively elaborate their dendritic arbors in distinct sublamina, where they receive, respectively, inputs from ON and OFF bipolar cells. During neonatal maturation, the bilaminarly distributed dendritic arbors of ON‐OFF retinal ganglion cells (RGCs) are refined to more narrowly localized monolaminar structures characteristic of ON or OFF RGCs. Recently, brain‐derived neurotrophic factor (BDNF) has been shown to regulate this laminar refinement, and to enhance the development of dendritic branches selectively of ON RGCs. Although other related neurotrophins are known to regulate neuronal process formation in the central nervous system, little is known about their action in maturing retina. Here, we report that overexpression of neurotrophin‐3 (NT‐3) in the eye accelerates RGC laminar refinement before eye opening. Furthermore, NT‐3 overexpression increases dendritic branch number but reduces dendritic elongation preferentially in ON‐OFF RGCs, a process that also occurs before eye opening. NT‐3 overexpression does affect dendritic maturation in ON RGCs, but to a much less degree. Taken together, our results suggest that NT‐3 and BDNF exhibit overlapping effects in laminar refinement but distinct RGC‐cell‐type specific effects in shaping dendritic arborization during postnatal development. J. Comp. Neurol. 514:449–458, 2009. © 2009 Wiley‐Liss, Inc.     

Immunohistological studies of metabotropic glutamate receptor subtype 6-deficient mice show no abnormality of retinal cell organization and ganglion cell maturation.

Immature retinal ganglion cells (RGCs) initially show a multistratified dendritic pattern, and, during the postnatal period, these dendrites gradually monostratify into ON and OFF sublaminae. The selective agonist of group III metabotropic glutamate receptors (mGluR), L-2-amino-4-phosphonobutyrate (L-AP-4), hyperpolarizes ON bipolar cells and reduces glutamate release. On the basis of L-AP-4-evoked inhibitory effects on ON-OFF segregation of developing RGCs, it has been hypothesized that glutamate-mediated synaptic activity is crucial for formation of the ON-OFF network. Gene-targeted ablation of mGluR6 specifically expressed in ON bipolar cells blocks normal ON responses but has been predicted to enhance glutamate release from ON bipolar cells. The mGluR6 knock-out mouse therefore provides a unique opportunity to investigate whether glutamate release and ON responses are important factors in the development of ON-OFF segregation. The combination of several different morphological analyses indicates that ON bipolar cells, as well as several distinct amacrine cells, in mGluR6 knock-out mice are normally distributed and correctly extend their terminals to defined retinal laminae. Importantly, both alpha and delta RGCs in adult mGluR6 knock-out mice are found monostratified into cell type-specific layers. Furthermore, no difference between wild-type and mGluR6 knock-out mice is observed in the maturation and dendritic stratification of developing RGCs. Hence, despite a deficit in normal ON responses, mGluR6 deficiency causes no abnormality in the retinal cellular organization nor in the stratifications of both ON bipolar cells and developing and mature RGCs. Based on these findings, we discuss several possible mechanisms that may underlie ON-OFF segregation of RGCs.     

ON cone bipolar cell axonal synapses in the OFF inner plexiform layer of the rabbit retina

Analysis of the rabbit retinal connectome RC1 reveals that the division between the ON and the OFF inner plexiform layer (IPL) is not structurally absolute. ON cone bipolar cells make noncanonical axonal synapses onto specific targets and receive amacrine cell synapses in the nominal OFF layer, creating novel motifs, including inhibitory crossover networks. Automated transmission electron microscopic imaging, molecular tagging, tracing, and rendering of ～400 bipolar cells reveals axonal ribbons in 36% of ON cone bipolar cells, throughout the OFF IPL. The targets include γ‐aminobutyrate (GABA)‐positive amacrine cells (γACs), glycine‐positive amacrine cells (GACs), and ganglion cells. Most ON cone bipolar cell axonal contacts target GACs driven by OFF cone bipolar cells, forming new architectures for generating ON–OFF amacrine cells. Many of these ON–OFF GACs target ON cone bipolar cell axons, ON γACs, and/or ON–OFF ganglion cells, representing widespread mechanisms for OFF to ON crossover inhibition. Other targets include OFF γACs presynaptic to OFF bipolar cells, forming γAC‐mediated crossover motifs. ON cone bipolar cell axonal ribbons drive bistratified ON–OFF ganglion cells in the OFF layer and provide ON drive to polarity‐appropriate targets such as bistratified diving ganglion cells (bsdGCs). The targeting precision of ON cone bipolar cell axonal synapses shows that this drive incidence is necessarily a joint distribution of cone bipolar cell axonal frequency and target cell trajectories through a given volume of the OFF layer. Such joint distribution sampling is likely common when targets are sparser than sources and when sources are coupled, as are ON cone bipolar cells. J. Comp. Neurol. 521:977–1000, 2013. © 2012 Wiley Periodicals, Inc.     

Two distinct types of ON directionally selective ganglion cells in the rabbit retina

Mammalian retinas contain about 20 types of ganglion cells that respond to different aspects of the visual scene, including the direction of motion of objects in the visual field. The rabbit retina has long been thought to contain two distinct types of directionally selective (DS) ganglion cell: a bistratified ON-OFF DS ganglion cell that responds to onset and termination of light, and an ON DS ganglion cell, which stratifies only in the ON layer and responds only to light onset. This division is challenged by targeted recordings from rabbit retina, which indicate that ON DS ganglion cells occur in two discriminably different types. One of these is strongly tracer-coupled to amacrine cells; the other is never tracer-coupled. These two types also differ in branching pattern, stratification depth, relative latency, and transience of spiking. The sustained, uncoupled ON DS cell ramifies completely within the lower cholinergic band and responds to nicotine with continuous firing. In contrast, the transient, coupled ON DS ganglion cell stratifies above the cholinergic band and is not positioned to receive major input from cholinergic amacrine cells, consistent with its modest response to the cholinergic agonist nicotine. Much data have accrued that directional responses in the mammalian retina originate via gamma-aminobutyric acid (GABA) release from the dendrites of starburst amacrine cells (Euler et al., 2002). If there is an ON DS ganglion cell that does not stratify in the starburst band, this suggests that its GABA-dependent directional signals may be generated by a mechanism independent of starburst amacrine cells.     

A functional organization of ON and OFF pathways in the rabbit retina

Intracellular electrophysiological recordings were obtained from amacrine and ganglion cells in an isolated, superfused retina-eyecup preparation of the rabbit. Cells were characterized physiologically, after which cell-staining was accomplished by intracellular iontophoresis of HRP. A computer-assisted image-processing system was used to study the dendritic stratification pattern of HRP-labeled neurons within the inner plexiform layer (IPL). Our results support the concept that the IPL is functionally divided into a distal OFF region and proximal ON layer. ON and OFF ganglion and amacrine cells show dendritic arborizations consistent with this division and ON-OFF ganglion cells have processes in both portions of the IPL. It appears that these functional subdivisions of the IPL reflect excitatory, but not necessarily inhibitory, inputs. Thus, the pattern of dendritic arborization of a cell appears to predict its physiological response polarity, regardless of the type of inhibition it receives.     

Synaptic inputs onto small bistratified (blue‐ON/yellow‐OFF) ganglion cells in marmoset retina

The inner plexiform layer of the retina contains functional subdivisions, which segregate ON and OFF type light responses. Here, we studied quantitatively the ON and OFF synaptic input to small bistratified (blue‐ON/yellow‐OFF) ganglion cells in marmosets (Callithrix jacchus). Small bistratified cells display an extensive inner dendritic tier that receives blue‐ON input from short‐wavelength‐sensitive (S) cones via blue cone bipolar cells. The outer dendritic tier is sparse and is thought to receive yellow‐OFF input from medium (M)‐ and long (L)‐wavelength‐sensitive cones via OFF diffuse bipolar cells. In total, 14 small bistratified cells from different eccentricities were analyzed. The cells were retrogradely labeled from the koniocellular layers of the lateral geniculate nucleus and subsequently photofilled. Retinal preparations were processed with antibodies against the C‐terminal binding protein 2, the AMPA receptor subunit GluR4, and/or gephyrin to identify bipolar and/or amacrine input. The results show that the synaptic input is evenly distributed across the dendritic tree, with a density similar to that reported previously for other ganglion cell types. The population of cells showed a consistent pattern, where bipolar input to the inner tier is about fourfold greater than bipolar input to the outer tier. This structural asymmetry of bipolar input may help to balance the weight of cone signals from the sparse S cone array against inputs from the much denser M/L cone array. J. Comp. Neurol. 517:655–669, 2009. © 2009 Wiley‐Liss, Inc.     

Selective synaptic connections in the retinal pathway for night vision

The mammalian retina encodes visual information in dim light using rod photoreceptors and a specialized circuit: rods→rod bipolar cells→AII amacrine cell. The AII amacrine cell uses sign-conserving electrical synapses to modulate ON cone bipolar cell terminals and sign-inverting chemical (glycinergic) synapses to modulate OFF cone cell bipolar terminals; these ON and OFF cone bipolar terminals then drive the output neurons, retinal ganglion cells (RGCs), following light increments and decrements, respectively. The AII amacrine cell also makes direct glycinergic synapses with certain RGCs, but it is not well established how many types receive this direct AII input. Here, we investigated functional AII amacrine→RGC synaptic connections in the retina of the guinea pig (Cavia porcellus) by recording inhibitory currents from RGCs in the presence of ionotropic glutamate receptor (iGluR) antagonists. This condition isolates a specific pathway through the AII amacrine cell that does not require iGluRs: cone→ON cone bipolar cell→AII amacrine cell→RGC. These recordings show that AII amacrine cells make direct synapses with OFF Alpha, OFF Delta and a smaller OFF transient RGC type that co-stratifies with OFF Alpha cells. However, AII amacrine cells avoid making synapses with numerous RGC types that co-stratify with the connected RGCs. Selective AII connections ensure that a privileged minority of RGC types receives direct input from the night-vision pathway, independent from OFF bipolar cell activity. Furthermore, these results illustrate the specificity of retinal connections, which cannot be predicted solely by co-stratification of dendrites and axons within the inner plexiform layer.     

Directional excitatory input to direction-selective ganglion cells in the rabbit retina

Directional responses in retinal ganglion cells are generated in large part by direction-selective release of γ-aminobutyric acid from starburst amacrine cells onto direction-selective ganglion cells (DSGCs). The excitatory inputs to DSGCs are also widely reported to be direction-selective, however, recent evidence suggests that glutamate release from bipolar cells is not directional, and directional excitation seen in patch-clamp analyses may be an artifact resulting from incomplete voltage control. Here, we test this voltage-clamp-artifact hypothesis in recordings from 62 ON-OFF DSGCs in the rabbit retina. The strength of the directional excitatory signal varies considerably across the sample of cells, but is not correlated with the strength of directional inhibition, as required for a voltage-clamp artifact. These results implicate additional mechanisms in generating directional excitatory inputs to DSGCs.     

Color vision and retinal chromatic information processing in teleost: A review

Teleosts exist under conditions where the intensity and spectral composition of available light is a function of media transmissivity, season, and geographic location. Moreover, the composition of a stimulus is dependent upon the object's direction and distance from the subject. Even should the same stimulus be presented repeatedly, the animal's ability to perceive it will be a function of temperature and season. Such diverse visual conditions have been dealt with (evolutionarily) by the development of specialized features such as a reflective tapetum, area and temperature dependent distribution of visual pigments, and an area-specific distribution of photoreceptor types.The cyprinid retina has a least 7 distinct photoreceptor types. Each of the photoreceptor types make synaptic contacts with bipolar and horizontal cells of one or more classes. There are at least 4 horizontal cell classes, 3 of which are thought to make color-specific feedback connections on photoreceptors. The receptors are not only the first neural retinal element, but also act as interneurons and display the first indication of antagonistic spectral and spatial response properties. Indeed, the complexity of the spectral response patterns observed within horizontal and receptor cells makes one wonder how information is sorted out in order to produce the high spectral and spatial resolution at the ganglion cell level. Two points must be kept in mind: (1) a photoreceptor's response is due primarily to quantum capture in that receptor's outer segment and is not due to horizontal cell feedback or inter-receptor connections; (2) bipolar cells form direct contacts with receptors and ganglion cells. The bipolar cells therefore provide a direct — straight-through — information transfer pathway.The importance of primary, direct neural pathways should not be underestimated. In general, the direct pathways, RECEPTOR→BIPOLAR→GANGLION CELL, provide the primary and most direct means of chromatic information transfer (Fig. 19). The secondary, internal, pathways, which include the horizontal and amacrine cells, are important only to the extent that they modify and contribute to both spectral and spatial contrast. The horizontal cells do contribute to the bipolar cell's surround properties, but the bipolar cell's greatest sensitivity and most dominant responses are within its central receptive field. The same can be said of the ganglion cells, their dominant response properties are to central field stimulation. The surround responses of both bipolars and ganglions are weak and temporally slow.The direct neural pathways can be subdivided into two systems which shall be termed the ON and OFF channels. Each of these channels consist of receptor, bipolar and ganglion cell combinations. These direct pathways are functionally defined by the response polarity of the bipolar and ganglion cell pair to a step increase in illumination. The ON pathways or channels consist of bipolar/ganglion cell combinations, each of which depolarizes to an increase in stimulus energy (+ΔI stimulus). Each component of the OFF pathways hyperpolarizes to the same stimulus. The ON and OFF pathways can also be identified anatomically. The ON pathways obviously make sign-inverting synapses between photoreceptors and bipolar cells, in order to transform the receptor's hyperpolarization into a depolarization: an ON response. The ON bipolar also terminates in only one lamina of the inner plexiform layer (layer b). The OFF pathways conserve the photoreceptors' hyperpolarizing response and the OFF bipolar cells terminate in sublamina ‘a’ of the IPL where they contact OFF ganglion cells. The ON and OFF pathways are believed to have different spectral sensitivities, with the ON channels representing the shorter wavelengths and the OFF channels favoring the longer wavelengths. The transfer of chromatic information is obviously more complex than simply ON and OFF responses.In addition to the independent ON and OFF pathways, some amacrine and ganglion cells receive input from both ON and OFF bipolars, forming the ON-OFF (transient) amacrine and ganglion cell classes. The ON-OFF cells terminate in both sublaminae of the IPL (Fig. 19). This combined input produces transient depolarizations to stimulus onset and cessation, due to the dominate depolarizing phase of the individual bipolar cell's response. The 3 identified ganglion cell types, ON, OFF, and ON-OFF may represent 3 distinct cell classes, or simply be components of a continuum with different ganglion cells contacting ON and OFF bipolar cells with different ratios. The continuum theory is supported by the observation that individual ganglion cells may produce ON, OFF, or ON-OFF responses depending on stimulus conditions, i.e., a ganglion cell's response may be altered by selecting stimulus conditions which favor ON or OFF bipolar cell types.The chromatic response properties of individual retinal neurons can best be described be defining which photoreceptor systems supply which interneurons. However, of all the bipolar cell types, only one or two have been adequately described in terms of receptor inputs. Moreover, no attempts have been made to define which bipolar cell types contact which ganglion cell classes. Therefore, it remains impossible to describe discrete (cell class to cell class) retinal chromatic pathways. It is impossible to determine the general response properties of such pathways by recording from ganglion cells. A spectrally/spatially defined ganglion cell permits one to deduce the spectral properties of the participating bipolar cells and whether they are ON or OFF units. With this information, the participating horizontal and receptor cell types can be described.The optic nerve may also affect chromatic information transfer. It is suggested that different size ganglion cells convey different chromatic information. Since there is a direct correlation between cell size and axon diameter and between axon diameter and conduction velocity, short versus long wavelength information may be transmitted to the CNS at different rates.Retinal ganglion cells project to and innervate numerous CNS structures. The optic tectum receives the majority of the projections. Even though numerous histological and functional studies on optic tectum have been reported, information on the response properties of individual cell types is non-existent. For example, the cytoarchitecture of the optic tectum is known, but no information is available on neural pathways or cellular interactions. We also do not know which CNS structures are involved in particular behavioral patterns.It is clear that different behavioral patterns are associated with different spectral sensitivities, i.e., spectral sensitivity is task dependent. Reflex type behaviors are apparently mediated by long wavelength stimuli, whereas more complex behaviors require differential integration across CNS structures and tend to be associated with medium and short wavelength stimuli. Data have been presented which suggest that spectral sensitivity is also a function of previous experience and may be altered during critical developmental periods. The major voids in our knowledge of chromatic information processing exist in CNS pathways, degree of task dependency and neural plasticity.     

Vsx1 regulates terminal differentiation of type 7 ON bipolar cells

Although retinal bipolar cells represent a morphologically well defined population of retinal interneurons, very little is known about the developmental mechanisms that regulate their processing. Furthermore, the identity of specific bipolar cell types that function in distinct visual circuits remains poorly understood. Here, we show that the homeobox gene Vsx1 is expressed in Type 7 ON bipolar cells. In the absence of Vsx1, Type 7 bipolar cells exhibit proper morphological specification but show defects in terminal gene expression. Vsx1 is required for the repression of bipolar cell-specific markers, including Calcium-binding protein 5 and Chx10. This contrasts its genetic requirement as an activator of gene expression in OFF bipolar cells. To assess possible ON signaling defects in Vsx1-null mice, we recorded specifically from ON-OFF directionally selective ganglion cells (DSGCs), which cofasciculate with Type 7 bipolar cell terminals. Vsx1-null ON-OFF DSGCs received more sustained excitatory synaptic input, possibly due to Type 7 bipolar cell defects. Interestingly, in Vsx1-null mice, the directionally selective circuit is functional but compromised. Together, these findings indicate that Vsx1 regulates terminal gene expression in Type 7 bipolar cells and is necessary for proper ON visual signaling within a directionally selective circuit.     

ON and OFF components of the receptive fields have different latencies to diffuse flashes of light in the superior colliculus of golden hamsters

Single unit activities were recorded from the superior colliculus in anesthetized hamsters. ON center and OFF center cells without surround showed short (within 150 ms) and long latency (longer than 150 ms) responses to diffuse flashes of light, respectively; ON and OFF center cells with an antagonistic surround and ON-OFF center cells showed both short and long latency responses. We suggest that the short latency discharges represent the activity on the ON component of the receptive field, while the long latency responses correspond to the OFF component. Thus, latencies of unit response to diffuse flashes of light may provide a useful indication of the existence of ON or OFF components in the receptive field.     

Gap-junction communication between subtypes of direction-selective ganglion cells in the developing retina

The On-Off direction-selective ganglion cells (DSGCs) in the rabbit retina comprise four distinct subtypes that respond preferentially to image motion in four orthogonal directions; each subtype forms a regular territorial array, which is overlapped by the other three arrays. In this study, ganglion cells in the developing retina were injected with Neurobiotin, a gap-junction-permeable tracer, and the DSGCs were identified by their characteristic type 1 bistratified (BiS1) morphology. The complex patterns of tracer coupling shown by the BiS1 ganglion cells changed systematically during the course of postnatal development. BiS1 cells appear to be coupled together around the time of birth, but, over the next 10 days, BiS1 cells decouple from each other, leading to the mature pattern in which only one subtype is coupled. At about postnatal day 5, before the ganglion cells become visually responsive, each of the BiS1 cells commonly showed tracer coupling both to a regular array of neighboring BiS1 cells, presumably destined to be DSGCs of the same subtype, and to a regular array of overlapping BiS1 cells, presumably destined to be DSGCs of a different subtype. The gap-junction intercellular communication between subtypes of DSGCs with different preferred directions may play an important role in the differentiation of their synaptic connectivity, with respect to either the inputs that DSGCs receive from retinal interneurons or the outputs that DSGCs make to geniculate neurons.     

Activity-regulated cell death contributes to the formation of ON and OFF α ganglion cell mosaics

At maturity, ON and OFF α ganglion cells in the cat retina are arrayed in regular mosaics, with adjacent cells commonly forming ON-OFF pairs. In the present study, we investigated the role of activity-mediated ganglion cell death in the formation of such cellular patterns. Because direct measures of ganglion cell mosaics are problematic in the developing retina, we examined the distributions of ON and OFF α cells in the postnatal cat retina by assessing the degree to which cells in closest proximity were of opposite sign (i.e., ON-OFF pairs). Computer simulations demonstrated that superimposition of two regular distributions results in a high incidence (∼90%) of opposite sign pairs. This is also the case for ON and OFF α cells in the mature retina, reflecting the high degree of regularity exhibited by this cell class. In contrast, during the first postnatal month, α cells displayed a much lower incidence of opposite sign pairs (∼60%), comparable to the superimposition of two simulated random distributions. We also show that there is a 20% loss of α cells in the central retina during postnatal development and that this magnitude of loss is sufficient to form regular distributions of ON and OFF cells. To assess the influence of sodium voltage-gated activity on this developmental process, intraocular injections of tetrodotoxin (TTX) were made during the postnatal period of α cell loss. When the TTX-treated animals reached maturity, there was a dose-related decrease in the incidence of opposite sign pairs, without any appreciable change in cell density. Moreover, the regularity index of ON and OFF cells was significantly lower than normal in the TTX-treated retinas. These findings demonstrate that a spatially selective pattern of ganglion cell loss contributes to the formation of regular ON and OFF ganglion cell distributions and that such cell loss is regulated by retinal activity. J. Comp. Neurol. 394:335–343, 1998. © 1998 Wiley-Liss, Inc.     

Theta ganglion cell type of cat retina

We define a new bistratified ganglion cell type of cat retina using intracellular staining in vitro. The theta cell has a small soma, slender axon, and delicate, highly branched dendritic arbor. Dendritic fields are intermediate in size among cat ganglion cells, with diameters typically two to three times those of beta cells. Fields increase in size with distance from the area centralis, ranging in diameter from 70 to 150 microns centrally to a maximum of 700 microns in the periphery. Theta cells have markedly smaller dendritic fields within the nasal visual streak than above or below it and smaller fields nasally than temporally. Dendritic arbors are narrowly bistratified. The outer arbor lies in the lower part of sublamina a (OFF sublayer) of the inner plexiform layer where it costratifies with the dendrites of OFF alpha cells. The inner arbor occupies the upper part of sublamina b (ON sublayer), where it costratifies with ON alpha dendrites. The outer and inner arbors are composed of many relatively short segments and are densely interconnected by branches that traverse the a/b sublaminar border. Experiments combining retrograde labeling with intracellular staining indicate that theta cells project to the superior colliculus and to two components of the dorsal lateral geniculate nucleus (the C laminae and medial interlaminar nucleus). Theta cells project contralaterally from the nasal retina and ipsilaterally from the temporal retina. They apparently correspond to a sluggish transient or phasic W-cell with an ON-OFF receptive field center.     

Morphology and connectivity of the small bistratified A8 amacrine cell in the mouse retina

Amacrine cells comprise ～30 morphological types in the mammalian retina. The synaptic connectivity and function of a few γ‐aminobutyric acid (GABA)ergic wide‐field amacrine cells have recently been studied; however, with the exception of the rod pathway‐specific AII amacrine cell, the connectivity of glycinergic small‐field amacrine cells has not been investigated in the mouse retina. Here, we studied the morphology and connectivity pattern of the small‐field A8 amacrine cell. A8 cells in mouse retina are bistratified with lobular processes in the ON sublamina and arboreal dendrites in the OFF sublamina of the inner plexiform layer. The distinct bistratified morphology was first visible at postnatal day 8, reaching the adult shape at P13, around eye opening. The connectivity of A8 cells to bipolar cells and ganglion cells was studied by double and triple immunolabeling experiments by using various cell markers combined with synaptic markers. Our data suggest that A8 amacrine cells receive glutamatergic input from both OFF and ON cone bipolar cells. Furthermore, A8 cells are coupled to ON cone bipolar cells by gap junctions, and provide inhibitory input via glycine receptor (GlyR) subunit α1 to OFF cone bipolar cells and to ON A‐type ganglion cells. Measurements of spontaneous glycinergic postsynaptic currents and GlyR immunolabeling revealed that A8 cells express GlyRs containing the α2 subunit. The results show that the bistratified A8 cell makes very similar synaptic contacts with cone bipolar cells as the rod pathway‐specific AII amacrine cell. However, unlike AII cells, A8 amacrine cells provide glycinergic input to ON A‐type ganglion cells. J. Comp. Neurol. 523:1529–1547, 2015. © 2015 Wiley Periodicals, Inc.     

Pathway-specific maturation, visual deprivation, and development of retinal pathway.

One of the fundamental features of the visual system is the segregation of neural circuits that process increments and decrements of luminance into ON and OFF pathways. In mature retina, the dendrites of retinal ganglion cells (RGCs) in the inner plexiform layer (IPL) of retina are separated into ON or OFF sublamina-specific stratification. At an early developmental stage, however, the dendrites of most RGCs are ramified throughout the IPL. The maturation of RGC ON/OFF dendritic stratification requires neural activities mediated by afferent inputs from bipolar and amacrine cells. The synchronized spontaneous burst activities in early postnatal developing retina regulate RGC dendritic filopodial movements and the maintenance or elimination of dendritic processes. After eye opening, visual experience further remodels and consolidates the retinal neural circuit into mature forms. Several neurotransmitter systems, including glutamatergic, acetylcholinergic, GABAergic, and glycinergic systems, might act together to modulate the RGC dendritic refinement. In addition, both the bipolar cells and cholinergic amacrine cells may provide laminar cues for the maturation of RGC dendritic stratification.