Homeostatic synaptic depression is achieved through a regulated decrease in presynaptic calcium channel abundance

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Abstract

Homeostatic signaling stabilizes synaptic transmission at the neuromuscular junction (NMJ) of Drosophila, mice, and human. It is believed that homeostatic signaling at the NMJ is bi-directional and considerable progress has been made identifying mechanisms underlying the homeostatic potentiation of neurotransmitter release. However, very little is understood mechanistically about the opposing process, homeostatic depression, and how bi-directional plasticity is achieved. Here we show that homeostatic potentiation and depression can be simultaneously induced, demonstrating true bi-directional plasticity. Next, we show that mutations that block homeostatic potentiation do not alter homeostatic depression, demonstrating that these are genetically separable processes. Finally, we show that homeostatic depression is achieved by decreased presynaptic calcium channel abundance and calcium influx, changes that are independent of the presynaptic action potential waveform. Thus, we identify a novel mechanism of homeostatic synaptic plasticity and propose a model that can account for the observed bi-directional, homeostatic control of presynaptic neurotransmitter release.

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Michael A Gaviño

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States

Competing interests
No competing interests declared.
Kevin J Ford

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States

Competing interests
No competing interests declared.
Santiago Archila

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States

Competing interests
No competing interests declared.
Graeme W Davis

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States

For correspondence
graeme.davis@ucsf.edu

Competing interests
Graeme W Davis, Reviewing editor, eLife.

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