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Silke Haverkamp - One of the best experts on this subject based on the ideXlab platform.
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connectivity map of Bipolar Cells and photoreceptors in the mouse retina
bioRxiv, 2016Co-Authors: Christian Behrens, Silke Haverkamp, Timm Schubert, Thomas Euler, Philipp BerensAbstract:Visual processing already starts at the very first synapse of the visual system. In the mouse retina, three different kinds of photoreceptors (M-cones, S-cones and rods) provide input to 14 parallel Bipolar Cell types. The precise pattern of connectivity between them determines which signals are available to downstream circuits and therefore the entire visual system. While it has been shown that cone Bipolar Cell types 1 contact M-cones and type 9 contacts S-cones selectively, most Bipolar Cell types are thought to contact all cones within their dendritic field. Also, ON Bipolar Cells are thought to contact cones exclusively via so-called invaginating synapses, while OFF Bipolar Cells are thought to form basal synapses. By mining publically available electron microscopy data, we confirm that there are no additional M- or S-cone selective Bipolar Cell types in the mouse retina; however, we found interesting violations of the established rules of outer retinal connectivity: Cone Bipolar Cell type X contacted only ~20% of the cones in its dendritic field and made mostly atypical non-invaginating contacts with cones. Types 5T, 5O and 8 also contacted fewer cones than expected from the extent of their dendritic field. In addition, we provide anatomical evidence that rod and cone pathways are interconnected in both directions: Not only OFF-types 3A, 3B and 4 get direct input from rods but also rod Bipolar Cells from cones. Together, this suggests that the organization of the outer plexiform layer is less straightforward than classically thought.
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Cell type specific Bipolar Cell input to ganglion Cells in the mouse retina
Neuroscience, 2016Co-Authors: Sonja Neumann, Laura Huser, K Ondreka, N Auler, Silke HaverkampAbstract:Many distinct ganglion Cell types, which are the output elements of the retina, were found to encode for specific features of a visual scene such as contrast, color information or movement. The detailed composition of retinal circuits leading to this tuning of retinal ganglion Cells, however, is apart from some prominent examples, largely unknown. Here we aimed to investigate if ganglion Cell types in the mouse retina receive selective input from specific Bipolar Cell types or if they sample their synaptic input non-selectively from all Bipolar Cell types stratifying within their dendritic tree. To address this question we took an anatomical approach and immunolabeled retinae of two transgenic mouse lines (GFP-O and JAM-B) with markers for ribbon synapses and type 2 Bipolar Cells. We morphologically identified all green fluorescent protein (GFP)-expressing ganglion Cell types, which co-stratified with type 2 Bipolar Cells and assessed the total number of Bipolar input synapses and the proportion of synapses deriving from type 2 Bipolar Cells. Only JAM-B ganglion Cells received synaptic input preferentially from Bipolar Cell types other than type 2 Bipolar Cells whereas the other analyzed ganglion Cell types sampled their Bipolar input most likely from all Bipolar Cell terminals within their dendritic arbor.
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immunohistochemical identification and synaptic inputs to the diffuse Bipolar Cell type db1 in macaque retina
The Journal of Comparative Neurology, 2011Co-Authors: Theresa Puthussery, Jacqueline Gayetprimo, Rowland W Taylor, Silke HaverkampAbstract:Detailed analysis of the synaptic inputs to the primate DB1 Bipolar Cell has been precluded by the absence of a suitable immunohistochemical marker. Here we demonstrate that antibodies for the EF-hand calcium-binding protein, secretagogin, strongly label the DB1 Bipolar Cell as well as a mixed population of GABAergic amacrine Cells in the macaque retina. Using secretagogin as a marker, we show that the DB1 Bipolar makes synaptic contact with both L/M as well as S-cone photoreceptors and only minimal contact with rod photoreceptors. Electron microscopy showed that the DB1 Bipolar makes flat contacts at both triad-associated and nontriad-associated positions on the cone pedicle. Double labeling with various glutamate receptor subunit antibodies failed to conclusively determine the subunit composition of the glutamate receptors on DB1 Bipolar Cells. In the IPL, DB1 Bipolar Cell axon terminals expressed the glycine receptor, GlyRα1, at sites of contact with AII amacrine Cells, suggesting that these Cells receive input from the rod pathway.
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Bipolar Cells of the ground squirrel retina
The Journal of Comparative Neurology, 2011Co-Authors: Christian Puller, K Ondreka, Silke HaverkampAbstract:Parallel processing of an image projected onto the retina starts at the first synapse, the cone pedicle, and each cone feeds its light signal into a minimum of eight different Bipolar Cell types. Hence, the morphological classification of Bipolar Cells is a prerequisite for analyzing retinal circuitry. Here we applied common Bipolar Cell markers to the cone-dominated ground squirrel retina, studied the labeling by confocal microscopy and electron microscopy, and compared the resulting Bipolar Cell types with those of the mouse (rod dominated) and primate retina. Eight different cone Bipolar Cell types (three OFF and five ON) and one rod Bipolar Cell were distinguished. The major criteria for classifying the Cells were their immunocytochemical identity, their dendritic branching pattern, and the shape and stratification level of their axons in the inner plexiform layer (IPL). Immunostaining with antibodies against Gγ13, a marker for ON Bipolar Cells, made it possible to separate OFF and ON Bipolars. Recoverin-positive OFF Bipolar Cells partly overlapped with ON Bipolar axon terminals at the ON/OFF border of the IPL. Antibodies against HCN4 labeled the S-cone selective (bb) Bipolar Cell. The calcium-binding protein CaB5 was expressed in two OFF and two ON cone Bipolar Cell types, and CD15 labeled a widefield ON cone Bipolar Cell comparable to the DB6 in primate. J. Comp. Neurol. 519:759–774, 2011. © 2010 Wiley-Liss, Inc.
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cone contacts mosaics and territories of Bipolar Cells in the mouse retina
The Journal of Neuroscience, 2009Co-Authors: Heinz Wässle, Christian Puller, Frank Muller, Silke HaverkampAbstract:We report a quantitative analysis of the different Bipolar Cell types of the mouse retina. They were identified in wild-type mice by specific antibodies or in transgenic mouse lines by specific expression of green fluorescent protein or Clomeleon. The Bipolar Cell densities, their cone contacts, their dendritic coverage, and their axonal tiling were measured in retinal whole mounts. The results show that each and all cones are contacted by at least one member of any given type of Bipolar Cell (not considering genuine blue cones). Consequently, each cone feeds its light signals into a minimum of 10 different Bipolar Cells. Parallel processing of an image projected onto the retina, therefore, starts at the first synapse of the retina, the cone pedicle. The quantitative analysis suggests that our proposed catalog of 11 cone Bipolar Cells and one rod Bipolar Cell is complete, and all major Bipolar Cell types of the mouse retina appear to have been discovered.
Heinz Wässle - One of the best experts on this subject based on the ideXlab platform.
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cone contacts mosaics and territories of Bipolar Cells in the mouse retina
The Journal of Neuroscience, 2009Co-Authors: Heinz Wässle, Christian Puller, Frank Muller, Silke HaverkampAbstract:We report a quantitative analysis of the different Bipolar Cell types of the mouse retina. They were identified in wild-type mice by specific antibodies or in transgenic mouse lines by specific expression of green fluorescent protein or Clomeleon. The Bipolar Cell densities, their cone contacts, their dendritic coverage, and their axonal tiling were measured in retinal whole mounts. The results show that each and all cones are contacted by at least one member of any given type of Bipolar Cell (not considering genuine blue cones). Consequently, each cone feeds its light signals into a minimum of 10 different Bipolar Cells. Parallel processing of an image projected onto the retina, therefore, starts at the first synapse of the retina, the cone pedicle. The quantitative analysis suggests that our proposed catalog of 11 cone Bipolar Cells and one rod Bipolar Cell is complete, and all major Bipolar Cell types of the mouse retina appear to have been discovered.
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type 4 off cone Bipolar Cells of the mouse retina express calsenilin and contact cones as well as rods
The Journal of Comparative Neurology, 2008Co-Authors: Silke Haverkamp, Heinz Wässle, Dana Specht, Sriparna Majumdar, Nikhat F Zaidi, Johann Helmut Brandstatter, Wilma Wasco, Susanne Tom DieckAbstract:Immunocytochemical discrimination of distinct Bipolar Cell types in the mouse retina is a prerequisite for analyzing retinal circuitry in wild-type and transgenic mice. Here we demonstrate that among the more than 10 anatomically defined mouse Bipolar Cell types, type 4 Bipolar Cells are specifically recognized by anti-calsenilin antibodies. Axon terminals in the inner plexiform layer are not readily identifiable because calsenilin is also expressed in a subset of amacrine and ganglion Cells. In contrast, in the outer plexiform layer calsenilin immunoreactivity allows the analysis of photoreceptor to type 4 Bipolar Cell contacts. A dense plexus of calsenilin-positive dendrites makes several basal contacts at cone pedicles. An individual calsenilin-positive Bipolar Cell contacts five to seven cones. In addition, some calsenilin-positive dendrites contact rod photoreceptors. On average we counted 10 rod spherule contacts per type 4 Bipolar Cell, and approximately 10% of rods contacted type 4 Bipolar Cells. We suggest that type 4 Bipolar Cells, together with the recently described type 3a and b Cells, provide an alternative and direct route from rods to OFF cone Bipolar Cells. In the Bassoon ΔEx4/5 mouse, a mouse mutant that shows extensive remodeling of the rod system including sprouting of horizontal and rod Bipolar Cells into the outer nuclear layer due to impaired synaptic transmission, we found that in addition mixed-input (type 3 and 4) OFF Bipolar Cells sprout to ectopic sites. In contrast, true cone-selective type 1 and 2 OFF cone Bipolar Cells did not show sprouting in the Bassoon mouse mutant. J. Comp. Neurol. 507: 1087–1101, 2008. © 2007 Wiley-Liss, Inc.
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types of Bipolar Cells in the mouse retina
The Journal of Comparative Neurology, 2004Co-Authors: Krishna K Ghosh, Silke Haverkamp, Sascha Bujan, Andreas Feigenspan, Heinz WässleAbstract:We studied the morphology of Bipolar Cells in fixed vertical tissue sections (slices) of the mouse retina by injecting the Cells with Lucifer Yellow and Neurobiotin. Nine different cone Bipolar Cell types and one rod Bipolar Cell type were distinguished. The major criteria for classifying the Cells were the branching pattern and stratification level of their axon terminals in the inner plexiform layer (IPL). To assess this, the IPL was subdivided into five strata of equal width. The slices were immunostained for calretinin, which labels three horizontal bands serving as a standard measure for the precise localization of the axon terminals. Immunostaining the retina with antibodies against the G-protein Ggamma13, a marker for ON-Bipolar Cells, made it possible to separate OFF- and ON-Bipolar Cells. At least two OFF-cone Bipolar Cells (Types 1 and 2) were immunolabeled with antibodies against the neurokinin 3 receptors (NK3R). A further OFF- and an ON-cone Bipolar Cell (Types 3 and 5) were immunostained with antibodies against the calcium-binding protein CaB5. The Bipolar Cell types described here were compared with previous schemes of rat and primate Bipolar Cells. Homologous types between the three species are discussed.
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immunocytochemical description of five Bipolar Cell types of the mouse retina
The Journal of Comparative Neurology, 2003Co-Authors: Silke Haverkamp, Arlene A Hirano, Krishna K Ghosh, Heinz WässleAbstract:With the ever-growing number of transgenic mice being used in vision research, a precise knowledge of the Cellular organization of the mouse retina is required. As with the cat, rabbit, rat, and primate retinae, as many as 10 cone Bipolar types and one rod Bipolar type can be expected to exist in the mouse retina; however, they still have to be defined. In the current study, several immunocytochemical markers were applied to sections of mouse retina, and the labeling of Bipolar Cells was studied using confocal microscopy and electron microscopy. By using antibodies against the neurokinin-3 receptor NK3R; the plasma membrane calcium ATPase1 (PMCA1); and the calcium (Ca)-binding proteins CaB1, CaB5, caldendrin, and recoverin, three different OFF-cone Bipolar Cells could be identified. One type of ON-cone Bipolar Cell was identified through its immunoreactivity for CaB5 and PMCA1. Rod Bipolar Cells, comparable in morphology to those of other mammalian retinae, expressed protein kinase Cα and CaB5. It was also shown that putative OFF-cone Bipolar Cells receive light signals through flat contacts at the cone pedicle base, whereas ON-cone Bipolar signaling involves invaginating contacts. The distribution of the kainate receptor subunit GluR5 was studied by confocal and electron microscopy. GluR5 was expressed at flat Bipolar Cell contacts; however, it appears to be involved with only certain types of OFF-cone Bipolar Cells. This suggests that different Bipolar Cell types receive their light signals through different sets of glutamate receptors.
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the synaptic complex of cones in the fovea and in the periphery of the macaque monkey retina
Vision Research, 1996Co-Authors: Myunghoon Chun, Paul R Martin, Ulrike Grunert, Heinz WässleAbstract:Parallel pathways for visual information processing start at the first synapse of the retina, at the cone pedicle. At least eight different types of Bipolar Cells receive direct synaptic input from an individual cone. The present study explores whether enough synaptic sites are available at the cone pedicle to supply all these Bipolar Cells. Monkey retinae were optimally fixed for electron microscopy. Serial horizontal sections were cut through the cone pedicle layer in a piece close to the fovea (eccentricity: 0.75 mm) and in a peripheral piece (eccentricity: 5-6 mm). The ribbon synapses (triads) at the cone pedicle base were analysed. The average number of synaptic ribbons per cone pedicle increased from 21.4 +/- 1.6 (n = 26) in central retina to 41.8 +/- 3 (n = 14) in peripheral retina. Five central and five peripheral pedicles were reconstructed and the invaginating Bipolar Cell dendrites forming the central elements of the triads were characterized. Close to the fovea an average of 18 invaginating Bipolar Cell dendrites was found, in peripheral retina the average was 90. Pedicles of foveal cones have one invaginating central process per ribbon, pedicles of peripheral cones have two. It is possible that midget Bipolar Cell dendrites occupy the majority of triads in the fovea, while in peripheral retina both midget and diffuse Bipolar Cell dendrites share the triads.
Neal S Peachey - One of the best experts on this subject based on the ideXlab platform.
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a missense mutation in grm6 reduces but does not eliminate mglur6 expression or rod depolarizing Bipolar Cell function
Journal of Neurophysiology, 2017Co-Authors: Neal S Peachey, Nazarul Hasan, Bernard Fitzmaurice, Samantha Burrill, Gobinda Pangeni, Son Yong Karst, Laura G Reinholdt, Melissa L BerryAbstract:This article describes a mouse model of the human disease complete congenital stationary night blindness in which the mutation reduces but does not eliminate GRM6 expression and Bipolar Cell functi...
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gpr179 is required for depolarizing Bipolar Cell function and is mutated in autosomal recessive complete congenital stationary night blindness
American Journal of Human Genetics, 2012Co-Authors: Neal S Peachey, Ralph J Florijn, Lucy B Rowe, Trijntje Sjoerdsma, Susana Contrerasalcantara, Kenkichi Baba, Gianluca Tosini, Nikita Pozdeyev, Michael P IuvoneAbstract:Complete congenital stationary night blindness (cCSNB) is a clinically and genetically heterogeneous group of retinal disorders characterized by nonprogressive impairment of night vision, absence of the electroretinogram (ERG) b-wave, and variable degrees of involvement of other visual functions. We report here that mutations in GPR179, encoding an orphan G protein receptor, underlie a form of autosomal-recessive cCSNB. The Gpr179nob5/nob5 mouse model was initially discovered by the absence of the ERG b-wave, a component that reflects depolarizing Bipolar Cell (DBC) function. We performed genetic mapping, followed by next-generation sequencing of the critical region and detected a large transposon-like DNA insertion in Gpr179. The involvement of GPR179 in DBC function was confirmed in zebrafish and humans. Functional knockdown of gpr179 in zebrafish led to a marked reduction in the amplitude of the ERG b-wave. Candidate gene analysis of GPR179 in DNA extracted from patients with cCSNB identified GPR179-inactivating mutations in two patients. We developed an antibody against mouse GPR179, which robustly labeled DBC dendritic terminals in wild-type mice. This labeling colocalized with the expression of GRM6 and was absent in Gpr179nob5/nob5 mutant mice. Our results demonstrate that GPR179 plays a critical role in DBC signal transduction and expands our understanding of the mechanisms that mediate normal rod vision.
Gautam B Awatramani - One of the best experts on this subject based on the ideXlab platform.
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intrinsic oscillatory activity arising within the electrically coupled aii amacrine on cone Bipolar Cell network is driven by voltage gated na channels
The Journal of Physiology, 2012Co-Authors: Stuart Trenholm, Joanna Borowska, Jiawei Zhang, Alex Hoggarth, Kyle Johnson, Steven Barnes, Timothy J Lewis, Gautam B AwatramaniAbstract:Key points • In mouse models for retinal degeneration, photoreceptor death leads to membrane oscillation in the remnant AII amacrine–ON cone Bipolar Cell network through an unknown mechanism. • We found such oscillations require voltage-gated Na+ channels and gap junctions but not hyperpolarization-activated currents (Ih). • Na+ channels are expressed predominantly in AII amacrine Cells and Ih in ON cone Bipolar Cells, and appear to interact via gap junctions to shape oscillations. • Similar intrinsic oscillations arose in the wild-type (wt) AII amacrine–ON cone Bipolar Cell network when photoreceptor inputs to Bipolar Cells were pharmacologically occluded. • Computational modelling captures experimental findings when a low level of Cellular heterogeneity is introduced in the coupled network. • These unique insights into the Cellular mechanisms underlying spontaneous activity in the degenerating retina might aid in designing the most effective strategies to restore vision using retinal prosthesis. Abstract In the rd1 mouse model for retinal degeneration, the loss of photoreceptors results in oscillatory activity (∼10–20 Hz) within the remnant electrically coupled network of retinal ON cone Bipolar and AII amacrine Cells. We tested the role of hyperpolarization-activated currents (Ih), voltage-gated Na+ channels and gap junctions in mediating such oscillatory activity. Blocking Ih (1 mm Cs+) hyperpolarized the network and augmented activity, while antagonizing voltage-dependent Na+ channels (1 μm TTX) abolished oscillatory activity in the AII amacrine–ON cone Bipolar Cell network. Voltage-gated Na+ channels were only observed in AII amacrine Cells, implicating these Cells as major drivers of activity. Pharmacologically uncoupling the network (200 μm meclofenamic acid (MFA)) blocked oscillations in all Cells indicating that Na+ channels exert their influence over multiple Cell types within the network. In wt retina, occluding photoreceptor inputs to Bipolar Cells (10 μm NBQX and 50 μm l-AP4) resulted in a mild (∼10 mV) hyperpolarization and the induction of oscillatory activity within the AII amacrine–ON cone Bipolar Cell network. These oscillations had similar properties to those observed in rd1 retina, suggesting that no major degeneration-induced network rewiring is required to trigger spontaneous oscillations. Finally, we constructed a simplified computational model that exhibited Na+ channel-dependent network oscillations. In this model, mild heterogeneities in channel densities between individual neurons reproduced our experimental findings. These results indicate that TTX-sensitive Na+ channels in AII amacrine Cells trigger degeneration-induced network oscillations, which provide a persistent synaptic drive to downstream remnant neurons, thus appearing to replace photoreceptors as the principal drivers of retinal activity.
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intrinsic oscillatory activity arising within the electrically coupled aii amacrine on cone Bipolar Cell network is driven by voltage gated na channels
The Journal of Physiology, 2012Co-Authors: Stuart Trenholm, Joanna Borowska, Jiawei Zhang, Alex Hoggarth, Kyle Johnson, Steven Barnes, Timothy J Lewis, Gautam B AwatramaniAbstract:In the rd1 mouse model for retinal degeneration, the loss of photoreceptors results in oscillatory activity (∼10–20 Hz) within the remnant electrically coupled network of retinal ON cone Bipolar and AII amacrine Cells. We tested the role of hyperpolarization-activated currents (I(h)), voltage-gated Na(+) channels and gap junctions in mediating such oscillatory activity. Blocking I(h) (1 mm Cs(+)) hyperpolarized the network and augmented activity, while antagonizing voltage-dependent Na(+) channels (1 μm TTX) abolished oscillatory activity in the AII amacrine-ON cone Bipolar Cell network. Voltage-gated Na(+) channels were only observed in AII amacrine Cells, implicating these Cells as major drivers of activity. Pharmacologically uncoupling the network (200 μm meclofenamic acid (MFA)) blocked oscillations in all Cells indicating that Na(+) channels exert their influence over multiple Cell types within the network. In wt retina, occluding photoreceptor inputs to Bipolar Cells (10 μm NBQX and 50 μm l-AP4) resulted in a mild (∼10 mV) hyperpolarization and the induction of oscillatory activity within the AII amacrine-ON cone Bipolar Cell network. These oscillations had similar properties to those observed in rd1 retina, suggesting that no major degeneration-induced network rewiring is required to trigger spontaneous oscillations. Finally, we constructed a simplified computational model that exhibited Na(+) channel-dependent network oscillations. In this model, mild heterogeneities in channel densities between individual neurons reproduced our experimental findings. These results indicate that TTX-sensitive Na(+) channels in AII amacrine Cells trigger degeneration-induced network oscillations, which provide a persistent synaptic drive to downstream remnant neurons, thus appearing to replace photoreceptors as the principal drivers of retinal activity.
Stuart Trenholm - One of the best experts on this subject based on the ideXlab platform.
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intrinsic oscillatory activity arising within the electrically coupled aii amacrine on cone Bipolar Cell network is driven by voltage gated na channels
The Journal of Physiology, 2012Co-Authors: Stuart Trenholm, Joanna Borowska, Jiawei Zhang, Alex Hoggarth, Kyle Johnson, Steven Barnes, Timothy J Lewis, Gautam B AwatramaniAbstract:Key points • In mouse models for retinal degeneration, photoreceptor death leads to membrane oscillation in the remnant AII amacrine–ON cone Bipolar Cell network through an unknown mechanism. • We found such oscillations require voltage-gated Na+ channels and gap junctions but not hyperpolarization-activated currents (Ih). • Na+ channels are expressed predominantly in AII amacrine Cells and Ih in ON cone Bipolar Cells, and appear to interact via gap junctions to shape oscillations. • Similar intrinsic oscillations arose in the wild-type (wt) AII amacrine–ON cone Bipolar Cell network when photoreceptor inputs to Bipolar Cells were pharmacologically occluded. • Computational modelling captures experimental findings when a low level of Cellular heterogeneity is introduced in the coupled network. • These unique insights into the Cellular mechanisms underlying spontaneous activity in the degenerating retina might aid in designing the most effective strategies to restore vision using retinal prosthesis. Abstract In the rd1 mouse model for retinal degeneration, the loss of photoreceptors results in oscillatory activity (∼10–20 Hz) within the remnant electrically coupled network of retinal ON cone Bipolar and AII amacrine Cells. We tested the role of hyperpolarization-activated currents (Ih), voltage-gated Na+ channels and gap junctions in mediating such oscillatory activity. Blocking Ih (1 mm Cs+) hyperpolarized the network and augmented activity, while antagonizing voltage-dependent Na+ channels (1 μm TTX) abolished oscillatory activity in the AII amacrine–ON cone Bipolar Cell network. Voltage-gated Na+ channels were only observed in AII amacrine Cells, implicating these Cells as major drivers of activity. Pharmacologically uncoupling the network (200 μm meclofenamic acid (MFA)) blocked oscillations in all Cells indicating that Na+ channels exert their influence over multiple Cell types within the network. In wt retina, occluding photoreceptor inputs to Bipolar Cells (10 μm NBQX and 50 μm l-AP4) resulted in a mild (∼10 mV) hyperpolarization and the induction of oscillatory activity within the AII amacrine–ON cone Bipolar Cell network. These oscillations had similar properties to those observed in rd1 retina, suggesting that no major degeneration-induced network rewiring is required to trigger spontaneous oscillations. Finally, we constructed a simplified computational model that exhibited Na+ channel-dependent network oscillations. In this model, mild heterogeneities in channel densities between individual neurons reproduced our experimental findings. These results indicate that TTX-sensitive Na+ channels in AII amacrine Cells trigger degeneration-induced network oscillations, which provide a persistent synaptic drive to downstream remnant neurons, thus appearing to replace photoreceptors as the principal drivers of retinal activity.
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intrinsic oscillatory activity arising within the electrically coupled aii amacrine on cone Bipolar Cell network is driven by voltage gated na channels
The Journal of Physiology, 2012Co-Authors: Stuart Trenholm, Joanna Borowska, Jiawei Zhang, Alex Hoggarth, Kyle Johnson, Steven Barnes, Timothy J Lewis, Gautam B AwatramaniAbstract:In the rd1 mouse model for retinal degeneration, the loss of photoreceptors results in oscillatory activity (∼10–20 Hz) within the remnant electrically coupled network of retinal ON cone Bipolar and AII amacrine Cells. We tested the role of hyperpolarization-activated currents (I(h)), voltage-gated Na(+) channels and gap junctions in mediating such oscillatory activity. Blocking I(h) (1 mm Cs(+)) hyperpolarized the network and augmented activity, while antagonizing voltage-dependent Na(+) channels (1 μm TTX) abolished oscillatory activity in the AII amacrine-ON cone Bipolar Cell network. Voltage-gated Na(+) channels were only observed in AII amacrine Cells, implicating these Cells as major drivers of activity. Pharmacologically uncoupling the network (200 μm meclofenamic acid (MFA)) blocked oscillations in all Cells indicating that Na(+) channels exert their influence over multiple Cell types within the network. In wt retina, occluding photoreceptor inputs to Bipolar Cells (10 μm NBQX and 50 μm l-AP4) resulted in a mild (∼10 mV) hyperpolarization and the induction of oscillatory activity within the AII amacrine-ON cone Bipolar Cell network. These oscillations had similar properties to those observed in rd1 retina, suggesting that no major degeneration-induced network rewiring is required to trigger spontaneous oscillations. Finally, we constructed a simplified computational model that exhibited Na(+) channel-dependent network oscillations. In this model, mild heterogeneities in channel densities between individual neurons reproduced our experimental findings. These results indicate that TTX-sensitive Na(+) channels in AII amacrine Cells trigger degeneration-induced network oscillations, which provide a persistent synaptic drive to downstream remnant neurons, thus appearing to replace photoreceptors as the principal drivers of retinal activity.