Maturation of a PKG-dependent retrograde mechanism for exoendocytic coupling of synaptic vesicles.

Kohgaku Eguchi, Setsuko Nakanishi, Hiroshi Takagi, Zacharie Taoufiq, Tomoyuki Takahashi

Cellular & Molecular Synaptic Function Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Kunigami, Okinawa 904-0412, Japan. eguchi@oist.jp

Neuron 2012 May 10

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At presynaptic terminals vesicular membranes are fused into plasma membrane upon exocytosis and retrieved by endocytosis. During a sustained high-frequency transmission, exoendocytic coupling is critical for the maintenance of synaptic transmission. Here, we show that this homeostatic coupling is supported by cGMP-dependent protein kinase (PKG) at the calyx of Held. This mechanism starts to operate after hearing onset during the second postnatal week, when PKG expression becomes upregulated in the brainstem. Pharmacological tests with capacitance measurements revealed that presynaptic PKG activity is supported by a retrograde signal cascade mediated by NO that is released by activation of postsynaptic NMDA receptors. Activation of PKG also upregulates phosphatidylinositol-4,5-bisphosphate, thereby accelerating endocytosis. Furthermore, presynaptic PKG activity upregulates synaptic fidelity during high-frequency transmission. We conclude that maturation of the PKG-dependent retrograde signal cascade strengthens the homeostatic plasticity for the maintenance of high-frequency synaptic transmission at the fast glutamatergic synapse. Copyright © 2012 Elsevier Inc. All rights reserved.

Citation

Kohgaku Eguchi, Setsuko Nakanishi, Hiroshi Takagi, Zacharie Taoufiq, Tomoyuki Takahashi. Maturation of a PKG-dependent retrograde mechanism for exoendocytic coupling of synaptic vesicles. Neuron. 2012 May 10;74(3):517-29