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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-08-24

AUTHORS

Florentina Soto, Adam Bleckert, Renate Lewis, Yunhee Kang, Daniel Kerschensteiner, Ann Marie Craig, Rachel OL Wong

ABSTRACT

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. More... »

PAGES

31

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1749-8104-6-31

DOI

http://dx.doi.org/10.1186/1749-8104-6-31

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1011334105

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21864334


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115 sites
116 spatial distribution
117 spontaneous inhibitory synaptic transmission
118 subunits
119 synapse density
120 synapses
121 synaptic markers
122 synaptic transmission
123 synaptogenesis
124 system
125 terminals
126 transgenic lines
127 transgenic mice
128 transmission
129 visual experience
130 vivo
131 γ2 subunit
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