Types Of Amacrine Cells Research Articles

Sidekick 2 directs formation of a retinal circuit that detects differential motion.

In the mammalian retina, processes of ~70 types of interneurons form specific synapses on ~30 types of retinal ganglion cells (RGCs) in a neuropil called the inner plexiform layer (IPL). Each RGC type extracts salient features from visual input, which are sent deeper into the brain for further processing 1-4. The specificity and stereotypy of synapses formed in the IPL account for the feature-detecting ability of the RGCs. Here, we analyze the development and function of synapses on one RGC type, the W3B-RGC5,6. These cells have the remarkable property of responding when the timing of a small object's movement differs from that of the background, but not when they coincide6. Such cells, called “local edge detectors” or “object motion sensors”, can distinguish moving objects from a visual scene that is also moving6-12. We show that W3B-RGCs receive strong and selective input from an unusual excitatory amacrine cell type called VG3-AC. Both W3B-RGCs and VG3-ACs express the immunoglobulin superfamily recognition molecule Sidekick-2 (Sdk2)13,14, and both loss- and gain-of function studies indicate that Sdk2-dependent homophilic interactions are necessary for the selectivity of the connection. The Sdk2-specified synapse is essential for visual responses of W3B-RGCs: whereas bipolar cells relay visual input directly to most RGCs, the W3B-RGCs receive much of their input indirectly, via the VG3-ACs. This non-canonical circuit introduces a delay into the pathway from photoreceptors in the center of the receptive field to W3B-RGCs, which could improve their ability to judge the synchrony of local and global motion.

Function and Circuitry of VIP+ Interneurons in the Mouse Retina.

The retina is a model system for understanding nervous system function. At the first stage, rod and cone photoreceptors encode light and communicate with a complex network of interneurons. These interneurons drive the responses of ganglion cells, which form the optic nerve and transmit visual information to the brain. Presently, we lack information about many of the retina's inhibitory amacrine interneurons. In this study, we used genetically modified mice to study the light responses and intercellular connections of specific amacrine cell types. The results show diversity in the shape and function of the studied amacrine cells and elucidate their connections with specific types of ganglion cell. The findings advance our understanding of the cellular basis for retinal function.

Tyrosine hydroxylase positive perisomatic rings are formed around various amacrine cell types in the mammalian retina.

Dopaminergic neurons of the central nervous system are mainly found in nuclei of the midbrain and the hypothalamus that provide subcortical and cortical targets with a rich and divergent innervation. Disturbance of signaling through this system underlies a variety of deteriorating conditions such as Parkinson's disease and schizophrenia. Although retinal dopaminergic signaling is largely independent of the above circuitry, malfunction of the retinal dopaminergic system has been associated with anomalies in visual adaptation and a number of retinal disorders. Dopamine (DA) is released mainly in a paracrine manner by a population of tyrosine hydroxylase expressing (TH(+) ) amacrine cells (AC) of the mammalian retina; thus DA reaches virtually all retinal cell types by diffusion. Despite this paracrine release, however, the so called AII ACs have been considered as the main targets of DA signaling owing to a characteristic and robust ring-like TH(+) innervation to the soma/dendritic-stalk area of AII cells. This apparent selectivity of TH(+) innervation seems to contradict the divergent DAergic signaling scheme of other brain loci. In this study, however, we show evidence for intimate proximity between TH(+) rings and somata of neurochemically identified non-AII cells. We also show that this phenomenon is not species specific, as we observe it in popular mammalian animal models including the rabbit, the rat, and the mouse. Finally, our dataset suggests the existence of further, yet unidentified post-synaptic targets of TH(+) dendritic rings. Therefore, we hypothesize that TH(+) ring-like structures target the majority of ACs non-selectively and that such contacts are wide-spread among mammals. Therefore, this new view of inner retinal TH(+) innervation resembles the divergent DAergic innervation of other brain areas through the mesolimbic, mesocortical, and mesostriatal signaling streams. AII amacrine cells have been considered as the main targets of dopamine signaling in the mammalian retina owing to a characteristic ring-like innervation from dopaminergic (TH(+) ) amacrine cells (green) to somata of AII cells (red). In this study, we show the intimate proximity of TH(+) rings and somata of non-AII cells, including starburst-a amacrine cells (blue) and other unidentified amacrine cells (magenta). We find that this phenomenon is not species specific and it occurs in a number of popular mammalian animal models. We hypothesize that TH(+) ring-inputs target most amacrine cells non-selectively and thus it resembles the divergent dopaminergic innervation of other brain areas.

Whole-exome sequencing reveals ZNF408 as a new gene associated with autosomal recessive retinitis pigmentosa with vitreal alterations.

Retinitis pigmentosa (RP) is a group of progressive inherited retinal dystrophies that cause visual impairment as a result of photoreceptor cell death. RP is heterogeneous, both clinically and genetically making difficult to establish precise genotype-phenotype correlations. In a Spanish family with autosomal recessive RP (arRP), homozygosity mapping and whole-exome sequencing led to the identification of a homozygous mutation (c.358_359delGT; p.Ala122Leufs*2) in the ZNF408 gene. A screening performed in 217 additional unrelated families revealed another homozygous mutation (c.1621C>T; p.Arg541Cys) in an isolated RP case. ZNF408 encodes a transcription factor that harbors 10 predicted C2H2-type fingers thought to be implicated in DNA binding. To elucidate the ZNF408 role in the retina and the pathogenesis of these mutations we have performed different functional studies. By immunohistochemical analysis in healthy human retina, we identified that ZNF408 is expressed in both cone and rod photoreceptors, in a specific type of amacrine and ganglion cells, and in retinal blood vessels. ZNF408 revealed a cytoplasmic localization and a nuclear distribution in areas corresponding with the euchromatin fraction. Immunolocalization studies showed a partial mislocalization of the p.Arg541Cys mutant protein retaining part of the WT protein in the cytoplasm. Our study demonstrates that ZNF408, previously associated with Familial Exudative Vitreoretinopathy (FEVR), is a new gene causing arRP with vitreous condensations supporting the evidence that this protein plays additional functions into the human retina.

Type 2 wide-field amacrine cells in TH::GFP mice show a homogenous synapse distribution and contact small ganglion cells.

In vertebrate retinas, wide-field amacrine cells represent a diverse class of interneurons, important for the extraction of selective features, like motion or objects, from the visual scene. Most types of wide-field amacrine cells lack dedicated output processes, whereas some types spatially segregate outputs from inputs. In the tyrosine hydroxylase (TH)::green fluorescent protein (GFP) mouse line, two types of GFP-expressing wide-field amacrine cells have been described: dopaminergic type 1 and γ-aminobutyric acid-ergic type 2 cells (TH2). TH2 cells possess short and long radial processes stratifying in the middle of the inner plexiform layer, where they collect excitatory and inhibitory inputs from bipolar cells and other amacrine cells, respectively. Although it was shown that these inputs lead to ON-OFF light responses, their spatial distribution along TH2 cell processes is unknown. Also, the postsynaptic targets of TH2 cells have not been identified so far. Here, we analysed the synapse distribution of these cells in TH::GFP mice and show that they form a weakly coupled network. Electrical synapses (made of connexin36) and chemical (excitatory and inhibitory) synapses are uniformly distributed along TH2 dendrites, independent of dendrite length or distance from soma. Moreover, we reveal that TH2 cells contact at least two types of small ganglion cells; one of them is the W3 cell, a ganglion cell sensitive to object motion. Contacts were often associated with markers of inhibitory synapses. Thus, TH2 wide-field amacrine cells likely provide postsynaptic inhibition to W3 ganglion cells and may contribute to object-motion detection in the mouse retina.

Identification of amacrine subtypes that express the atypical cadherin celsr3

We previously identified Celsr3, an atypical cadherin, as essential for normal inhibitory circuit formation in the inner retina. Its absence during retinal development leads to increases in GABA receptor numbers on ON-bipolar cell terminals and consequent changes in retinal physiology, but does not cause obvious cell spacing or synaptic lamination defects. This study focuses on defining the subset of amacrine cells that express celsr3 during development of the wild type zebrafish retina. We have developed a BAC transgene expressing EGFP under the control of celsr3 promoter, Tg(celsr3:EGFP). Similar to the retinal expression of the endogenous gene, the transgene is expressed in amacrine, ganglion and bipolar, but not horizontal or photoreceptor cells. We transiently expressed the BAC in zebrafish larvae and categorized 104 celsr3 expressing amacrine cells based on their shape, arborization and lamination. Ten different amacrine cell types express Tg(celsr3:EGFP). These include narrow, medium and wide-field types of varicose cells. There are many multistratified cells, including one not previously identified and a few specific types of monostratified amacrine cells. Non-varicose amacrine cells do not express the transgene. We propose that celsr3 expression in varicose amacrine cells is key to this molecule's function in circuitry formation during retinal development. The BAC transgene we have developed provides a useful tool to study Celsr3 function.

Functional regulation of neuronal nitric oxide synthase expression and activity in the rat retina

In the nervous system within physiological conditions, nitric oxide (NO) production depends on the activity of nitric oxide synthases (NOSs), and particularly on the expression of the neuronal isoform (nNOS). In the sensory systems, the role of NO is poorly understood. In this study, we identified nNOS-positive cells in the inner nuclear layer (INL) of the rat retina, with distinct characteristics such as somata size, immunolabeling level and location. Employing mathematical cluster analysis, we determined that nNOS amacrine cells are formed by two distinct populations. We next investigated the molecular identity of these cells, which did not show colocalization with calbindin (CB), choline acetyltransferase (ChAT), parvalbumin (PV) or protein kinase C (PKC), and only partial colocalization with calretinin (CR), revealing the accumulation of nNOS in specific amacrine cell populations. To access the functional, circuitry-related roles of these cells, we performed experiments after adaptation to different ambient light conditions. After 24h of dark-adaptation, we detected a subtle, yet statistically significant decrease in nNOS transcript levels, which returned to steady-state levels after 24h of normal light–dark cycle, revealing that nNOS expression is governed by ambient light conditions. Employing electron paramagnetic resonance (EPR), we demonstrated that dark-adaptation decreases NO production in the retina. Furthermore, nNOS accumulation changed in the dark-adapted retinas, with a general reduction in the inner plexiform layer. Finally, computational analysis based on clustering techniques revealed that dark-adaptation differently affected both types of nNOS-positive amacrine cells. Taken together, our data disclosed functional regulation of nNOS expression and activity, disclosing new circuitry-related roles of nNOS-positive cells. More importantly, this study indicated unsuspected roles for NO in the sensory systems, particularly related to adaptation to ambient demands.

Genetically targeted binary labeling of retinal neurons.

A major stumbling block to understanding neural circuits is the extreme anatomical and functional diversity of interneurons. Subsets of interneurons can be targeted for manipulation using Cre mouse lines, but Cre expression is rarely confined to a single interneuron type. It is essential to have a strategy that further restricts labeling in Cre driver lines. We now describe an approach that combines Cre driver mice, recombinant adeno-associated virus, and rabies virus to produce sparse but binary labeling of select interneurons--frequently only a single cell in a large region. We used this approach to characterize the retinal amacrine and ganglion cell types in five GABAergic Cre mouse (Mus musculus) lines, and identified two new amacrine cell types: an asymmetric medium-field type and a wide-field type. We also labeled several wide-field amacrine cell types that have been previously identified based on morphology but whose connectivity and function had not been systematically studied due to lack of genetic markers. All Cre-expressing amacrine cells labeled with an antibody to GABA. Cre-expressing RGCs lacked GABA labeling and included classically defined as well as recently identified types. In addition to the retina, our technique leads to sparse labeling of neurons in the cortex, lateral geniculate nucleus, and superior colliculus, and can be used to express optogenetic tools such as channelrhodopsin and protein sensors such as GCaMP. The Cre drivers identified in this study provide genetic access to otherwise hard to access cell types for systematic analysis including anatomical characterization, physiological recording, optogenetic and/or chemical manipulation, and circuit mapping.

DSCAM localization and function at the mouse cone synapse

The Down syndrome cell adhesion molecule (DSCAM) is required for regulation of cell number, soma spacing, and cell type-specific dendrite avoidance in many types of retinal ganglion and amacrine cells. In this study we assay the organization of cells making up the outer plexiform layer of the retina in the absence of Dscam. Some types of OFF bipolar cells, type 3b and type 4 bipolar cells, had defects in dendrite arborization in the Dscam mutant retina, whereas other cell types appeared similar to wild type. The cone synapses that these cells project their dendrites to were intact, as visualized by electron microscopy, and had a distribution and density that was not significantly different from that of wild type. The spacing of type 3b bipolar cell dendrites was further analyzed by Voronoi domain analysis, density recovery profiling (DRP) analysis, and nearest neighbor analysis. Spacing was found to be significantly different when wild-type and mutant type 3b bipolar cell dendrites were compared. Defects in arborization of these bipolar cells could not be attributed to the disorganization of inner plexiform layer cells that occurs in the Dscam mutant retina or an increase in cell number, as they arborized when Dscam was targeted in retinal ganglion cells only or in the bax null retina. Localization of DSCAM was assayed and the protein was localized near to cone synapses in mouse, macaque, and ground squirrel retinas. DSCAM protein was detected in several types of bipolar cells, including type 3b and type 4 bipolar cells.

Urocortin 2 treatment is protective in excitotoxic retinal degeneration

Urocortin 2 (Ucn 2) is a corticotrop releasing factor paralog peptide with many physiological functions and it has widespread distribution. There are some data on the cytoprotective effects of Ucn 2, but less is known about its neuro- and retinoprotective actions. We have previously shown that Ucn 2 is protective in ischemia-induced retinal degeneration. The aim of the present study was to examine the protective potential of Ucn 2 in monosodium-glutamate (MSG)-induced retinal degeneration by routine histology and to investigate cell-type specific effects by immunohistochemistry. Rat pups received MSG applied on postnatal days 1, 5 and 9 and Ucn 2 was injected intravitreally into one eye. Retinas were processed for histology and immunocytochemistry after 3 weeks. Immunolabeling was determined for glial fibrillary acidic protein, vesicular glutamate transporter 1, protein kinase Cα, calbindin, parvalbumin and calretinin. Retinal tissue from animals treated with MSG showed severe degeneration compared to normal retinas, but intravitreal Ucn 2 treatment resulted in a retained retinal structure both at histological and neurochemical levels: distinct inner retinal layers and rescued inner retinal cells (different types of amacrine and rod bipolar cells) could be observed. These findings support the neuroprotective function of Ucn 2 in MSG-induced retinal degeneration.

Characterization of secretagogin‐immunoreactive amacrine cells in marmoset retina

The retina contains at least 30 different types of amacrine cells but not many are well characterized. In the present study the calcium-binding protein secretagogin was localized in a population of regular and displaced amacrine cells in the retina of the common marmoset Callithrix jacchus. Irrespective of their soma location, the dendrites of secretagogin amacrine cells occupy strata 2, 3, and 4 of the inner plexiform layer, between the two bands formed by cholinergic amacrine cells. Segretagogin amacrine cells are also immunopositive to antibodies against glutamic acid decarboxylase, suggesting that they use γ-aminobutyric acid (GABA) as their neurotransmitter. The spatial density of secretagogin amacrine cells decreases from a peak of about 400 cells/mm(2) near 1 mm eccentricity to less than 100 cells/mm(2) in peripheral retina; these densities account for about 1% of amacrine cells in the inner nuclear layer and for up to 27% of displaced amacrine cells. The cell bodies form a regular mosaic, suggesting that they constitute a single amacrine cell population. Secretagogin cells have varicose dendrites, which are decorated with small spines. Intracellular injection of DiI into secretagogin cells revealed an average dendritic field diameter of 170 μm and an average coverage factor of 3.2. In summary, secretagogin cells in marmoset retina are medium-field amacrine cells that share their stratification pattern with narrow-field amacrine cells and their neurotransmitter with wide-field amacrine cells. They may mediate spatial inhibition spanning the centralmost (on and off) bands of the inner plexiform layer.

Morphological and physiological properties of enhanced green fluorescent protein (EGFP)‐expressing wide‐field amacrine cells in the ChAT‐EGFP mouse line

Mammalian retinas comprise a variety of interneurons, among which amacrine cells represent the largest group, with more than 30 different cell types each exhibiting a rather distinctive morphology and carrying out a unique function in retinal processing. However, many amacrine types have not been studied systematically because, in particular, amacrine cells with large dendritic fields, i.e. wide-field amacrine cells, have a low abundance and are therefore difficult to target. Here, we used a transgenic mouse line expressing the coding sequence of enhanced green fluorescent protein under the promoter for choline acetyltransferase (ChAT-EGFP mouse) and characterized a single wide-field amacrine cell population monostratifying in layer 2/3 of the inner plexiform layer (WA-S2/3 cell). Somata of WA-S2/3 cells are located either in the inner nuclear layer or are displaced to the ganglion cell layer and exhibit a low cell density. Using immunohistochemistry, we show that WA-S2/3 cells are presumably GABAergic but may also release acetylcholine as their somata are weakly positive for ChAT. Two-photon-guided patch-clamp recordings from intact retinas revealed WA-S2/3 cells to be ON-OFF cells with a homogenous receptive field even larger than the dendritic field. The large spatial extent of the receptive field is most likely due to the extensive homologous and heterologous coupling among WA-S2/3 cells and to other amacrine cells, respectively, as indicated by tracer injections. In summary, we have characterized a novel type of GABAergic ON-OFF wide-field amacrine cell which is ideally suited to providing long-range inhibition to ganglion cells due to its strong coupling.

Characterization of small‐field bistratified amacrine cells in macaque retina labeled by antibodies against synaptotagmin‐2

Macaque retinae were immunostained with monoclonal antibodies directed against the protein synaptotagmin-2 (Syt2). Syt2 was localized in a population of small-field amacrine cells, whose cell bodies formed a regular mosaic within the inner nuclear layer, indicating they represent a single amacrine cell type. The labeled amacrine cells had a bistratified appearance with a dense dendritic plexus in the OFF-layer and only a few lobular processes extending into the ON-layer of the inner plexiform layer, similar to A8 amacrine cells described in cat and human retina. Syt2-labeled cells were immunoreactive for glycine but lacked immunoreactivity for γ-aminobutyric acid (GABA), suggesting they use glycine as their neurotransmitter. The density of these cells increases from ∼200/mm(2) in peripheral retina to ∼1,400/mm(2) in central retina. Their bipolar cell input was studied by immunolabeling experiments using various bipolar cell markers combined with CtBP2, a marker of presynaptic ribbons. Our data show that Syt2-labeled amacrine cells receive input from both OFF and ON cone bipolar cells, as well as from rod bipolar cells. The OFF input is dominated by the diffuse bipolar cell DB1 (44%) and the OFF midget bipolar cell (38%). Here we describe a population of bistratified small-field amacrine cells closely resembling A8 amacrine cells and their cone-dominated bipolar cell input. J. Comp. Neurol. 521:709-724, 2013. © 2012 Wiley Periodicals, Inc.

Divergence of visual channels in the inner retina

Bipolar cells form parallel channels that carry visual signals from the outer to the inner retina. Each type of bipolar cell is thought to carry a distinct visual message to select types of amacrine cells and ganglion cells. However, the number of ganglion cell types exceeds that of the bipolar cells providing their input, suggesting that bipolar cell signals diversify on transmission to ganglion cells. We explored in the salamander retina how signals from individual bipolar cells feed into multiple ganglion cells and found that each bipolar cell was able to evoke distinct responses among ganglion cells, differing in kinetics, adaptation and rectification properties. This signal divergence resulted primarily from interactions with amacrine cells that allowed each bipolar cell to send distinct signals to its target ganglion cells. Our findings indicate that individual bipolar cell-ganglion cell connections have distinct transfer functions. This expands the number of visual channels in the inner retina and enhances the computational power and feature selectivity of early visual processing.

Receptor targets of amacrine cells

Amacrine cells are a morphologically and functionally diverse group of inhibitory interneurons. Morphologically, they have been divided into approximately 30 types. Although this diversity is probably important to the fine structure and function of the retinal circuit, the amacrine cells have been more generally divided into two subclasses. Glycinergic narrow-field amacrine cells have dendrites that ramify close to their somas, cross the sublaminae of the inner plexiform layer, and create cross talk between its parallel ON and OFF pathways. GABAergic wide-field amacrine cells have dendrites that stretch long distances from their soma but ramify narrowly within an inner plexiform layer sublamina. These wide-field cells are thought to mediate inhibition within a sublamina and thus within the ON or OFF pathway. The postsynaptic targets of all amacrine cell types include bipolar, ganglion, and other amacrine cells. Almost all amacrine cells use GABA or glycine as their primary neurotransmitter, and their postsynaptic receptor targets include the most common GABA(A), GABA(C), and glycine subunit receptor configurations. This review addresses the diversity of amacrine cells, the postsynaptic receptors on their target cells in the inner plexiform layer of the retina, and some of the inhibitory mechanisms that arise as a result. When possible, the effects of GABAergic and glycinergic inputs on the visually evoked responses of their postsynaptic targets are discussed.

Physiological characterization and functional heterogeneity of narrow‐field mammalian amacrine cells

Light-evoked responses of 106 morphologically identified narrow-field amacrine cells (ACs) were studied in dark-adapted mouse retinal slices. Forty-five cells exhibit AIIAC morphology, 55% of which show characteristic AIIAC physiological properties (AIIAC1s) and the remaining 45% display different physiological responses, suggesting that AIIACs are functionally heterogeneous. Moreover, we found that 42 cells exhibit morphology that resembles the seven morphological types of glycine-positive ACs (GlyAC1-7) reported in the rat retina, and for the first time assigned light response and function properties to these morphological types of glycinergic ACs in the mouse retina. In addition, five narrow-field ACs exhibited morphology resembling that of the GlyAC5 or GlyAC7 but with different physiological responses (GlyAC5(#) and GlyAC7(#)). Therefore, the eight morphological types of narrow-field ACs exhibit 12 classes of physiological responses. Furthermore, we found ACs whose physiological responses were indistinguishable from those of GlyAC3 or GlyAC4s but with different morphology (GlyAC3* or GlyAC4*). These observations suggest that although the majority of narrow-field mammalian ACs forms discrete functional groups that correlate with their morphology, a significant number of these cells with similar morphology do not display the same light responses, and some with similar light responses do not exhibit the same morphology.

NeuroD Factors Regulate Cell Fate and Neurite Stratification in the Developing Retina

Members of the basic helix-loop-helix (bHLH) family of transcription factors have been shown to control critical aspects of development in many tissues. To identify bHLH genes that might regulate specific aspects of retinal cell development, we investigated the expression of bHLH genes in single, developing mouse retinal cells, with particular emphasis on the NeuroD family. Two of these factors, NeuroD2 and NeuroD6/NEX, had not been previously reported as expressed in the retina. A series of loss- and gain-of-function experiments was performed, which suggested that NeuroD genes have both similarities and differences in their activities. Notably, misexpression of NeuroD genes can direct amacrine cell processes to two to three specific sublaminae in the inner plexiform layer. This effect is specific to cell type and NeuroD gene, as the AII amacrine cell type is refractory to the effects of NeuroD1 and NeuroD6, but uniquely sensitive to the effect of NeuroD2 on neurite targeting. Additionally, NeuroD2 is endogenously expressed in AII amacrine cells, among others, and loss of NeuroD2 function results in a partial loss of AII amacrine cells. The effects of misexpressing NeuroD genes on retinal cell fate determination also suggested shared and divergent functions. Remarkably, NeuroD2 misexpression induced ganglion cell production even after the normal developmental window of ganglion cell genesis. Together, these data suggest that members of the NeuroD family are important for neuronal cell type identity and may be involved in several cell type-specific aspects of retinal development, including fate determination, differentiation, morphological development, and circuit formation.

Regional distribution of nitrergic neurons in the inner retina of the chicken

Using both NADPH diaphorase and anti-nNOS antibodies, we have identified-from retinal flatmounts-neuronal types in the inner retina of the chicken that are likely to be nitrergic. The two methods gave similar results and yielded a total of 15 types of neurons, comprising 9 amacrine cells, 5 ganglion cells, and 1 centrifugal midbrain neuron. Six of these 15 cell types are ubiquitously distributed, comprising 3 amacrine cells, 2 displaced ganglion cells, and a presumed orthotopic ganglion cell. The remaining nine cell types are regionally restricted within the retina. As previously reported, efferent fibers of midbrain neurons and their postsynaptic partners, the unusual axon-bearing target amacrine cells, are entirely confined to the ventral retina. Also confined to the ventral retina, though with somewhat different distributions, are the "bullwhip" amacrine cells thought to be involved in eye growth, an orthotopic ganglion cell, and two types of large axon-bearing amacrine cells whose dendrites and axons lie in stratum 1 of the inner plexiform layer (IPL). Intracellular fills of these two cell types showed that only a minority of otherwise morphologically indistinguishable neurons are nitrergic. Two amacrine cells that branch throughout the IPL are confined to an equatorial band, and one small-field orthotopic ganglion cell that branches in the proximal IPL is entirely dorsal. These findings suggest that the retina uses different processing on different regions of the visual image, though the benefit of this is presently obscure.

Mechanism and circuitry underlying retinal sensitization

AbstractRecently we have described a population of retinal ganglion cells that increase their sensitivity after the presentation of a high contrast stimulus. This process, termed contrast sensitization is a form of short-term information storage that enables ganglion cells to store the location of a previously moving object for several seconds. Effectively, sensitizing ganglion cells make a prediction that the location of a strong stimulus at one point in time will continue to be important in the near future, even after the strong stimulus ceases. To understand how the retina can paradoxically increase its sensitivity in the face of a strong stimulus, we recorded intracellularly from sensitizing ganglion cells, and found that a depolarization of the baseline membrane potential underlies the increase in sensitivity. We then fit the membrane potential fluctuations with a model that contained two independently adapting pathways: one excitatory and one inhibitory. In this model, a strong stimulus adapts the inhibitory pathway, such that subsequent stimuli are processed with less inhibition, thus increasing sensitivity. Consistent with this model, pharmacologically blocking GABAergic inhibitory transmission eliminated sensitization. To identify interneurons that generated sensitization, we recorded intracellularly from an inhibitory amacrine cell, while simultaneously recording from a population of ganglion cells with an extracellular multielectrode array. By injecting current into the amacrine cell, we measured whether amacrine transmission changed during sensitization. Initial results indicate the presence of an amacrine cell whose transmission to ganglion cells depresses during sensitization, as predicted by the model. This effect was specific, as other types of amacrine cells did not change their transmission under the same conditions. These results lead to an understanding of sensitization whereby a strong stimulus primes the circuit to form a prediction of future input by locally removing one type of inhibition.

Mechanism and circuitry underlying retinal sensitization

Recently we have described a population of retinal ganglion cells that increase their sensitivity after the presentation of a high contrast stimulus. This process, termed contrast sensitization is a form of short-term information storage that enables ganglion cells to store the location of a previously moving object for several seconds. Effectively, sensitizing ganglion cells make a prediction that the location of a strong stimulus at one point in time will continue to be important in the near future, even after the strong stimulus ceases. To understand how the retina can paradoxically increase its sensitivity in the face of a strong stimulus, we recorded intracellularly from sensitizing ganglion cells, and found that a depolarization of the baseline membrane potential underlies the increase in sensitivity. We then fit the membrane potential fluctuations with a model that contained two independently adapting pathways: one excitatory and one inhibitory. In this model, a strong stimulus adapts the inhibitory pathway, such that subsequent stimuli are processed with less inhibition, thus increasing sensitivity. Consistent with this model, pharmacologically blocking GABAergic inhibitory transmission eliminated sensitization. To identify interneurons that generated sensitization, we recorded intracellularly from an inhibitory amacrine cell, while simultaneously recording from a population of ganglion cells with an extracellular multielectrode array. By injecting current into the amacrine cell, we measured whether amacrine transmission changed during sensitization. Initial results indicate the presence of an amacrine cell whose transmission to ganglion cells depresses during sensitization, as predicted by the model. This effect was specific, as other types of amacrine cells did not change their transmission under the same conditions. These results lead to an understanding of sensitization whereby a strong stimulus primes the circuit to form a prediction of future input by locally removing one type of inhibition.