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Author Notes:

Correspondence: Peter Wenner, pwenner@emory.edu

Conceived and designed the experiments: PW CL.

Performed the experiments: CL CG.

Analyzed the data: PW CL CG.

Wrote the paper: PW CL.

Peter Wenner is on the PLOS ONE Editorial Board.

We thank Dr. Michael O'Donovan for his valuable comments on the manuscript.

This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


Research Funding:

Neurological Disorders and Stroke - NS065992, NS065992-03S1 Whitehall Foundation - Grant # 2010-05-42, Neilsen Foundation - Grant # 161414.

Activity Blockade and GABAA Receptor Blockade Produce Synaptic Scaling through Chloride Accumulation in Embryonic Spinal Motoneurons and Interneurons


Journal Title:



Volume 9, Number 4


, Pages e94559-e94559

Type of Work:

Article | Final Publisher PDF


Synaptic scaling represents a process whereby the distribution of a cell's synaptic strengths are altered by a multiplicative scaling factor. Scaling is thought to be a compensatory response that homeostatically controls spiking activity levels in the cell or network. Previously, we observed GABAergic synaptic scaling in embryonic spinal motoneurons following in vivo blockade of either spiking activity or GABAA receptors (GABAARs). We had determined that activity blockade triggered upward GABAergic scaling through chloride accumulation, thus increasing the driving force for these currents. To determine whether chloride accumulation also underlies GABAergic scaling following GABAAR blockade we have developed a new technique. We expressed a genetically encoded chloride-indicator, Clomeleon, in the embryonic chick spinal cord, which provides a non-invasive fast measure of intracellular chloride. Using this technique we now show that chloride accumulation underlies GABAergic scaling following blockade of either spiking activity or the GABAAR. The finding that GABAAR blockade and activity blockade trigger scaling via a common mechanism supports our hypothesis that activity blockade reduces GABAAR activation, which triggers synaptic scaling. In addition, Clomeleon imaging demonstrated the time course and widespread nature of GABAergic scaling through chloride accumulation, as it was also observed in spinal interneurons. This suggests that homeostatic scaling via chloride accumulation is a common feature in many neuronal classes within the embryonic spinal cord and opens the possibility that this process may occur throughout the nervous system at early stages of development.

Copyright information:

© 2014 Lindsly et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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