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Neural Development

, 9:25

First Online: 07 November 2014Received: 09 June 2014Accepted: 20 October 2014


BackgroundSpontaneous retinal activity SRA is important during eye-specific segregation within the dorsal lateral geniculate nucleus dLGN, but the features of activity critical for retinogeniculate refinement are controversial. Pharmacologically or genetically manipulating cholinergic signaling during SRA perturbs correlated retinal ganglion cell RGC spiking and disrupts eye-specific retinofugal refinement in vivo, consistent with an instructive role for SRA during visual system development. Paradoxically, ablating the starburst amacrine cells SACs that generate cholinergic spontaneous activity disrupts correlated RGC firing without impacting retinal activity levels or eye-specific segregation in the dLGN. Such experiments suggest that patterned SRA during retinal waves is not critical for eye-specific refinement and instead, normal activity levels are permissive for retinogeniculate development. Here we revisit the effects of ablating the cholinergic network during eye-specific segregation and show that SAC ablation disrupts, but does not eliminate, retinal waves with no concomitant impact on normal eye-specific segregation in the dLGN.

ResultsWe induced SAC ablation in postnatal ferret pups beginning at birth by intraocular injection of a novel immunotoxin selective for the ferret vesicular acetylcholine transporter Ferret VAChT-Sap. Through dual-patch whole-cell and multi-electrode array recording we found that SAC ablation altered SRA patterns and led to significantly smaller retinal waves compared with controls. Despite these defects, eye-specific segregation was normal. Further, interocular competition for target territory in the dLGN proceeded in cases where SAC ablation was asymmetric in the two eyes.

ConclusionsOur data demonstrate normal eye-specific retinogeniculate development despite significant abnormalities in patterned SRA. Comparing our current results with earlier studies suggests that defects in retinal wave size, absolute levels of SRA, correlations between RGC pairs, RGC burst frequency, high frequency RGC firing during bursts, and the number of spikes per RGC burst are each uncorrelated with abnormalities in eye-specific segregation in the dLGN. An increase in the fraction of asynchronous spikes occurring outside of bursts and waves correlates with eye-specific segregation defects in studies reported to date. These findings highlight the relative importance of different features of SRA while providing additional constraints for computational models of Hebbian plasticity mechanisms in the developing visual system.

KeywordsRetinogeniculate Eye-specific segregation Retinal wave Spontaneous activity Retinal ganglion cell Dorsal lateral geniculate nucleus Abbreviationsß2KOA line of transgenic mice with the ß2 subunit of the nicotinic acetylcholine receptor knocked out

ß2TGA line of transgenic mice in which ß2 subunit of the nicotinic acetylcholine receptor expression is limited to the ganglion cell layer of the retina

ß2-nAChRThe ß2 subunit of the nicotinic acetylcholine receptor

ChATCholine acetyltransferase

dLGNDorsal lateral geniculate nucleus

MEMEEagle’s minimum essential media


MEAMulti-electrode array

NSnot significant

OCTOptimal Cutting Temperature Medium

P0Postnatal day zero

P2Postnatal day two

P4Postnatal day four

P6Postnatal day six

P8Postnatal day eight

P10Postnatal day 10


RGCRetinal ganglion cell

SACStarburst amacrine cell


SEMstandard error of the mean

SRASpontaneous retinal activity

VAChTVesicular acetylcholine transporter.

Electronic supplementary materialThe online version of this article doi:10.1186-1749-8104-9-25 contains supplementary material, which is available to authorized users.

Colenso M Speer, Chao Sun, Barbara Chapman contributed equally to this work.

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Autor: Colenso M Speer - Chao Sun - Lauren C Liets - Ben K Stafford - Barbara Chapman - Hwai-Jong Cheng

Fuente: https://link.springer.com/

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