Inter-spike mitochondrial Ca²⁺ release enhances high frequency synaptic transmission

Area of Science:

• Neuroscience
• Cell Biology
• Synaptic Physiology

Background:

• Mitochondrial calcium (Ca2+) buffering locally regulates synaptic transmission.
• The occurrence and role of mitochondrial Ca2+ release (MCR) during high-frequency stimulation (HFS) remain largely unknown.

Purpose of the Study:

• To investigate the role of MCR via the mitochondrial Na+/Ca2+ exchanger (mNCX) in short-term plasticity during HFS.
• To determine if MCR influences synaptic transmission under physiological extracellular Ca2+ concentrations.

Main Methods:

• Utilized tetraphenylphosphonium (TPP+), a specific inhibitor of mNCX, at the calyx of Held synapse in rat.
• Assessed short-term facilitation (STF) and excitatory postsynaptic currents (EPSCs) during HFS.
• Measured presynaptic mitochondrial Ca2+ levels.

Main Results:

• TPP+ significantly reduced STF and steady-state EPSCs at mature calyx synapses under physiological extracellular Ca2+ (1.2 mM).
• These effects were correlated with increased presynaptic mitochondrial Ca2+ accumulation during HFS.
• MCR enhanced vesicular release probability without altering global presynaptic Ca2+ transients.

Conclusions:

• MCR, mediated by mNCX, contributes to short-term facilitation at the calyx of Held synapse.
• Intra-train MCR elevates local Ca2+ near synaptic sites, enhancing release probability and supporting high-frequency neurotransmission.
• Mitochondrial Ca2+ release plays a crucial role in maintaining stable synaptic transmission under physiological conditions.