Abstract
Long-term synaptic changes, which are essential for learning and memory, are dependent on homeostatic mechanisms that stabilize neural activity. Homeostatic responses have also been implicated in pathological conditions, including nicotine addiction. Although multiple homeostatic pathways have been described, little is known about how compensatory responses are tuned to prevent them from overshooting their optimal range of activity. We found that prolonged inhibition of nicotinic acetylcholine receptors (nAChRs), the major excitatory receptors in the Drosophila CNS, resulted in a homeostatic increase in the Drosophila α7 (Dα7)-nAChR. This response then induced an increase in the transient A-type K+ current carried by Shaker cognate L (Shal; also known as voltage-gated K+ channel 4, Kv4) channels. Although increasing Dα7-nAChRs boosted miniature excitatory postsynaptic currents, the ensuing increase in Shal channels served to stabilize postsynaptic potentials. These data identify a previously unknown mechanism for fine tuning the homeostatic response.
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Acknowledgements
We thank G. Waro for genetic crosses and technical assistance. We thank H. Bellen (Baylor College of Medicine) for the antibody to Dα7 and the Dα7-deficient mutant line, S. Sigrist (Institute for Biology/Genetics) for the UAS–nAcRα-18C-EGFP fly line, M. Fujioka (Thomas Jefferson University) for the RRa-GAL4, RN2-GAL4 and EL-GAL4 fly lines, S. Singh (State University of New York, Buffalo) for the Shab[3] line, and E. Gundelfinger and U. Thomas (Leibniz Institute for Neurobiology) for the antibodies to Drosophila nAChRs. We also thank C. Yeung for carrying out genetic mapping and crosses for the transgenic HA-Shal line. S.T. is supported by a grant from the US National Institutes of Health (R01 GM083335).
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Y.P. conducted all of the experiments and analyzed all of the data. S.T. supervised the project and wrote the majority of the manuscript.
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Ping, Y., Tsunoda, S. Inactivity-induced increase in nAChRs upregulates Shal K+ channels to stabilize synaptic potentials. Nat Neurosci 15, 90–97 (2012). https://doi.org/10.1038/nn.2969
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DOI: https://doi.org/10.1038/nn.2969
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