Presynaptic Mitochondria Communicate With Release Sites for Spatio-Temporal Regulation of Exocytosis at the Motor Nerve Terminal

Mario Lopez-Manzaneda; Andrea Fuentes-Moliz; Lucia Tabares

doi:10.3389/fnsyn.2022.858340

Presynaptic Mitochondria Communicate With Release Sites for Spatio-Temporal Regulation of Exocytosis at the Motor Nerve Terminal

Front Synaptic Neurosci. 2022 May 12:14:858340. doi: 10.3389/fnsyn.2022.858340. eCollection 2022.

Authors

Mario Lopez-Manzaneda¹, Andrea Fuentes-Moliz¹, Lucia Tabares¹

Affiliation

¹ Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, Seville, Spain.

Abstract

Presynaptic Ca²⁺ regulation is critical for accurate neurotransmitter release, vesicle reloading of release sites, and plastic changes in response to electrical activity. One of the main players in the regulation of cytosolic Ca²⁺ in nerve terminals is mitochondria, which control the size and spread of the Ca²⁺ wave during sustained electrical activity. However, the role of mitochondria in Ca²⁺ signaling during high-frequency short bursts of action potentials (APs) is not well known. Here, we studied spatial and temporal relationships between mitochondrial Ca²⁺ (mCa²⁺) and exocytosis by live imaging and electrophysiology in adult motor nerve terminals of transgenic mice expressing synaptophysin-pHluorin (SypHy). Our results show that hot spots of exocytosis and mitochondria are organized in subsynaptic functional regions and that mitochondria start to uptake Ca²⁺ after a few APs. We also show that mitochondria contribute to the regulation of the mode of fusion (synchronous and asynchronous) and the kinetics of release and replenishment of the readily releasable pool (RRP) of vesicles. We propose that mitochondria modulate the timing and reliability of neurotransmission in motor nerve terminals during brief AP trains.

Keywords: active zones; asynchronous release; calcium; exocytosis; mitochondria; neuromuscular junction; synapse; synchronous release.