Presynaptic calcium concentration microdomains and transmitter release

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Neurotransmitter release is a fundamental process in synaptic transmission.
• Calcium influx is a known trigger for neurotransmitter release at presynaptic terminals.
• The precise localization and concentration of calcium at release sites remain areas of investigation.

Purpose of the Study:

• To investigate the spatial and quantitative aspects of calcium dynamics during neurotransmitter release.
• To identify the specific locations within the presynaptic terminal where calcium triggers transmitter release.
• To correlate calcium concentration changes with the active zones responsible for synaptic transmission.

Main Methods:

• Injection of the calcium-sensitive luminescent protein, n-Aequorin J, into the squid giant synapse preterminal fiber.
• Stimulation of the presynaptic terminal to induce neurotransmitter release.
• Monitoring and mapping light emission from n-Aequorin J as an indicator of calcium concentration changes.

Main Results:

• Light emission, signifying calcium influx, was observed at well-defined sites within the active zones of the presynaptic terminal.
• These luminescent sites (quantum emission domains or QEDs) were consistently located across repeated stimuli.
• The distribution, size, and number of QEDs corresponded directly with the active zones and their number.

Conclusions:

• Neurotransmitter release is initiated by highly localized calcium concentration changes, potentially reaching several hundred micromoles.
• These calcium events occur at specific, invariant locations within the active zones of the presynaptic terminal.
• The findings provide direct evidence for the precise spatial regulation of calcium-triggered exocytosis.