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Optogenetic silencing strategies differ in their effects on inhibitory synaptic transmission

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Abstract

Optogenetic silencing using light-driven ion fluxes permits rapid and effective inhibition of neural activity. Using rodent hippocampal neurons, we found that silencing activity with a chloride pump can increase the probability of synaptically evoked spiking after photoactivation; this did not occur with a proton pump. This effect can be accounted for by changes to the GABAA receptor reversal potential and demonstrates an important difference between silencing strategies.

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Figure 1: Optogenetic silencing strategies differ in their effects on synaptically evoked spiking activity.
Figure 2: A light-activated Cl pump, but not a H+ pump, causes a sustained change in GABAergic transmission.

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Acknowledgements

We thank P. Bolam (Oxford University) for resources, and K. Deisseroth (Stanford University) and E. Boyden (Massachusetts Institute of Technology) for DNA constructs. We also thank G. Miesenböck, D. Kätzel and B. Richards for comments. Supported by a grant from the Medical Research Council (G0601503); research leading to these results received funding under the European Community's Seventh Framework Programme (FP7/2007-2013).

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J.V.R. and C.J.A. designed the research. J.V.R., T.J.E. and L.K. performed the experiments. J.V.R. and C.J.A. analyzed the data. J.V.R. and C.J.A. wrote the paper.

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Correspondence to Colin J Akerman.

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The authors declare no competing financial interests.

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Raimondo, J., Kay, L., Ellender, T. et al. Optogenetic silencing strategies differ in their effects on inhibitory synaptic transmission. Nat Neurosci 15, 1102–1104 (2012). https://doi.org/10.1038/nn.3143

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