Early maturation of GABAergic synapses in mouse retinal ganglion cells

Unsoeld, Thomas; Stradomska, Alicja; Wang, Rui; Rathjen, Fritz G.; Jüttner, René

doi:10.1016/j.ijdevneu.2007.12.001

Cited by 8 publications

(9 citation statements)

References 38 publications

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“…However, ribbon synapses, characteristic of bipolar cells, are not present until P11, after which they also increase at an equivalent rate [18]. Indeed, functional drive from amacrine cells develops prior to glutamatergic transmission from bipolar cells [55]. Our previous studies separately mapping excitatory and inhibitory postsynaptic sites on individual RGCs also suggested that inhibitory and excitatory synaptogenesis may be coordinated during development to balance inhibition and excitation after glutamatergic synaptogenesis begins, at least for one RGC type [15], [26].…”

Section: Discussionmentioning

confidence: 92%

Spatial Relationships between GABAergic and Glutamatergic Synapses on the Dendrites of Distinct Types of Mouse Retinal Ganglion Cells across Development

Bleckert

Parker

Kang³

et al. 2013

PLoS ONE

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Neuronal output requires a concerted balance between excitatory and inhibitory (I/E) input. Like other circuits, inhibitory synaptogenesis in the retina precedes excitatory synaptogenesis. How then do neurons attain their mature balance of I/E ratios despite temporal offset in synaptogenesis? To directly compare the development of glutamatergic and GABAergic synapses onto the same cell, we biolistically transfected retinal ganglion cells (RGCs) with PSD95CFP, a marker of glutamatergic postsynaptic sites, in transgenic Thy1YFPγ2 mice in which GABAA receptors are fluorescently tagged. We mapped YFPγ2 and PSD95CFP puncta distributions on three RGC types at postnatal day P12, shortly before eye opening, and at P21 when robust light responses in RGCs are present. The mature IGABA/E ratios varied among ON-Sustained (S) A-type, OFF-S A-type, and bistratified direction selective (DS) RGCs. These ratios were attained at different rates, before eye-opening for ON-S and OFF-S A-type, and after eye-opening for DS RGCs. At both ages examined, the IGABA/E ratio was uniform across the arbors of the three RGC types. Furthermore, measurements of the distances between neighboring PSD95CFP and YFPγ2 puncta on RGC dendrites indicate that their local relationship is established early in development, and cannot be predicted by random organization. These close spatial associations between glutamatergic and GABAergic postsynaptic sites appear to represent local synaptic arrangements revealed by correlative light and EM reconstructions of a single RGC's dendrites. Thus, although RGC types have different IGABA/E ratios and establish these ratios at separate rates, the local relationship between excitatory and inhibitory inputs appear similarly constrained across the RGC types studied.

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Section: Discussionmentioning

confidence: 92%

Spatial Relationships between GABAergic and Glutamatergic Synapses on the Dendrites of Distinct Types of Mouse Retinal Ganglion Cells across Development

Bleckert

Parker

Kang³

et al. 2013

PLoS ONE

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“…For example, in the hippocampus, the apical dendrite of CA1 pyramidal cells is first contacted by GABAergic inteneurons prior to extension of these dendrites into the stratum lacunosum-moleculare, where they later receive input from glutamatergic afferents of the perforant pathway [4,5]. Likewise, RGCs also obtain GABAergic and glycinergic drive from amacrine cells prior to the formation of glutamatergic synapses from bipolar cells [51] (but see [52]). Unlike hippocampal pyramidal cells where dendrites need to reach available glutamatergic afferents, the delay in glutamatergic synaptogenesis onto RGCs is because bipolar cells are generated much later than amacrine cells.…”

Section: Discussionmentioning

confidence: 99%

Coordinated increase in inhibitory and excitatory synapses onto retinal ganglion cells during development

et al. 2011

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BackgroundNeuronal output is shaped by a balance of excitation and inhibition. How this balance is attained in the central nervous system during development is not well understood, and is complicated by the fact that, in vivo, GABAergic and glycinergic synaptogenesis precedes that of glutamatergic synapses. Here, we determined the distributions of inhibitory postsynaptic sites on the dendritic arbors of individual neurons, and compared their developmental patterns with that of excitatory postsynaptic sites. We focused on retinal ganglion cells (RGCs), the output neurons of the retina, which receive excitatory input from bipolar cells and inhibitory input from amacrine cells. To visualize and map inhibitory postsynaptic sites, we generated transgenic mice in which RGCs express fluorescently tagged Neuroligin 2 (YFP-NL2) under the control of the Thy1 promoter. By labeling RGC dendrites biolistically in YFP-NL2-expressing retinas, we were able to map the spatial distribution and thus densities of inhibitory postsynaptic sites on the dendritic arbors of individual large-field RGCs across ages.ResultsWe demonstrate that YFP-NL2 is present at inhibitory synapses in the inner plexiform layer by its co-localization with gephyrin, the γ2 subunit of the GABAA receptor and glycine receptors. YFP-NL2 puncta were apposed to the vesicular inhibitory transmitter transporter VGAT but not to CtBP2, a marker of presynaptic ribbons found at bipolar cell terminals. Similar patterns of co-localization with synaptic markers were observed for endogenous NL2. We also verified that expression of YFP-NL2 in the transgenic line did not significantly alter spontaneous inhibitory synaptic transmission onto RGCs. Using these mice, we found that, on average, the density of inhibitory synapses on individual arbors increased gradually until eye opening (postnatal day 15). A small centro-peripheral gradient in density found in mature arbors was apparent at the earliest age we examined (postnatal day 8). Unexpectedly, the adult ratio of inhibitory/excitatory postsynaptic sites was rapidly attained, shortly after glutamatergic synaptogenesis commenced (postnatal day 7).ConclusionOur observations suggest that bipolar and amacrine cell synaptogenesis onto RGCs appear coordinated to rapidly attain a balanced ratio of excitatory and inhibitory synapse densities prior to the onset of visual experience.

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“…Both GABA and glycine are already localized within neurons at the time of birth in rodent retina, whereas expression of glutamate appears diffuse around birth until about a week after birth (Fletcher and Kalloniatis, 1997). GABA A -specific spontaneous postsynaptic currents can be recorded from retinal ganglion cells as early as embryonic day 17 (Unsoeld et al, 2008). Spontaneous excitatory postsynaptic currents (EPSCs), on the other hand, can be recorded from mouse retinal ganglion cells only around P7 (Johnson et al, 2003; Morgan et al, 2008).…”

Section: Synapse Structure and Connectivity Of Retinal Neuronsmentioning

confidence: 99%

Functional architecture of the retina: Development and disease

Hoon

Okawa

Santina

et al. 2014

Progress in Retinal and Eye Research

467

385

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Structure and function are highly correlated in the vertebrate retina, a sensory tissue that is organized into cell layers with microcircuits working in parallel and together to encode visual information. All vertebrate retinas share a fundamental plan, comprising five major neuronal cell classes with cell body distributions and connectivity arranged in stereotypic patterns. Conserved features in retinal design have enabled detailed analysis and comparisons of structure, connectivity and function across species. Each species, however, can adopt structural and/or functional retinal specializations, implementing variations to the basic design in order to satisfy unique requirements in visual function. Recent advances in molecular tools, imaging and electrophysiological approaches have greatly facilitated identification of the cellular and molecular mechanisms that establish the fundamental organization of the retina and the specializations of its microcircuits during development. Here, we review advances in our understanding of how these mechanisms act to shape structure and function at the single cell level, to coordinate the assembly of cell populations, and to define their specific circuitry. We also highlight how structure is rearranged and function is disrupted in disease, and discuss current approaches to re-establish the intricate functional architecture of the retina.

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Early maturation of GABAergic synapses in mouse retinal ganglion cells

Cited by 8 publications

References 38 publications

Spatial Relationships between GABAergic and Glutamatergic Synapses on the Dendrites of Distinct Types of Mouse Retinal Ganglion Cells across Development

Spatial Relationships between GABAergic and Glutamatergic Synapses on the Dendrites of Distinct Types of Mouse Retinal Ganglion Cells across Development

Coordinated increase in inhibitory and excitatory synapses onto retinal ganglion cells during development

Functional architecture of the retina: Development and disease

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