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


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 Doc2?/?, 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. Doc2? promoted glutamatergic minis, while Doc2? 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.

SUBMITTER: Courtney NA 

PROVIDER: S-EPMC6090561 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Excitatory and Inhibitory Neurons Utilize Different Ca<sup>2+</sup> Sensors and Sources to Regulate Spontaneous Release.

Courtney Nicholas A NA   Briguglio Joseph S JS   Bradberry Mazdak M MM   Greer Christina C   Chapman Edwin R ER  

Neuron 20180510 5


Spontaneous neurotransmitter release (mini) is an important form of Ca<sup>2+</sup>-dependent synaptic transmission that occurs in the absence of action potentials. A molecular understanding of this process requires an identification of the underlying Ca<sup>2+</sup> sensors. Here, we address the roles of the relatively low- and high-affinity Ca<sup>2+</sup> sensors, synapotagmin-1 (syt1) and Doc2α/β, respectively. We found that both syt1 and Doc2 regulate minis, but, surprisingly, their relativ  ...[more]

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