Excitatory and Inhibitory Neurons Utilize Different Ca2+ Sensors and Sources to Regulate Spontaneous Release

Neuron
Nicholas A CourtneyEdwin R Chapman

Abstract

Spontaneous neurotransmitter release (mini) is an important form of Ca2+-dependent synaptic transmission that occurs in the absence of action potentials. A molecular understanding of this process requires an identification of the underlying Ca2+ sensors. Here, we address the roles of the relatively low- and high-affinity Ca2+ sensors, synapotagmin-1 (syt1) and Doc2α/β, respectively. We found that both syt1 and Doc2 regulate minis, but, surprisingly, their relative contributions depend on whether release was from excitatory or inhibitory neurons. Doc2α promoted glutamatergic minis, while Doc2β and syt1 both regulated GABAergic minis. We identified Ca2+ ligand mutations in Doc2 that either disrupted or constitutively activated the regulation of minis. Finally, Ca2+ entry via voltage-gated Ca2+ channels triggered miniature GABA release by activating syt1, but had no effect on Doc2-driven minis. This work reveals an unexpected divergence in the regulation of spontaneous excitatory and inhibitory transmission in terms of both Ca2+ sensors and sources.

Citations

Feb 9, 2019·The Journal of Physiology·Ege T Kavalali
Jun 8, 2019·ELife·Justin J GrassmeyerWallace B Thoreson
Sep 11, 2019·Nature Communications·Nicholas A CourtneyEdwin R Chapman
Oct 7, 2019·Journal of Neurochemistry·Kelly VargaLiang-Wei Gong
Jul 10, 2020·Journal of Neurochemistry·Debra AbramovJacqueline Burré
Feb 28, 2019·Frontiers in Cellular Neuroscience·Andrei RozovFliza Valiullina-Rakhmatullina
Jun 18, 2020·Frontiers in Immunology·Marwa SleimanJens Rettig
Aug 8, 2018·Frontiers in Synaptic Neuroscience·Claire Guerrier, David Holcman
Mar 12, 2019·Frontiers in Molecular Neuroscience·Magdalena MajVerena Tretter
Dec 12, 2019·F1000Research·Michael C. Andresen
Oct 9, 2019·Scientific Reports·Quentin Bourgeois-JaarsmaAlexander J Groffen
Feb 12, 2021·The Journal of Cell Biology·Lei LiZhitao Hu
Feb 25, 2021·Proceedings of the National Academy of Sciences of the United States of America·Chungwon ParkHyokeun Park
Feb 24, 2021·Cellular and Molecular Life Sciences : CMLS·Mónica C Quiñones-Frías, J Troy Littleton
Jul 15, 2020·Current Opinion in Neurobiology·Anne C Wolfes, Camin Dean
May 5, 2020·Neuron·Mazdak M BradberryEdwin R Chapman

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