Fusion pore flux controls the rise-times of quantal synaptic responses

Area of Science:

• Neuroscience
• Cell Biology
• Biophysics

Background:

• Neurotransmitter release from synaptic vesicles generates quantal responses, such as miniature excitatory postsynaptic currents (mEPSCs) at excitatory synapses.
• mEPSCs are crucial for synaptic transmission, but the factors governing their precise characteristics are not fully understood.

Purpose of the Study:

• To investigate the relationship between mEPSC amplitude and rise-time.
• To identify the underlying biophysical mechanisms responsible for observed variations in mEPSC properties.
• To develop a model that accurately recapitulates experimental mEPSC data.

Main Methods:

• Analysis of mEPSCs in cultured mouse hippocampal neurons and HEK cells.
• Development and application of computational models to simulate mEPSC generation.
• Comparison of experimental data with model predictions based on different biophysical parameters.

Main Results:

• mEPSC amplitude and rise-time varied significantly across different cell types and within individual cells.
• A positive correlation between mEPSC amplitude and rise-time was observed, particularly in neurons.
• Modeling demonstrated that the fusion pore expulsion time, dependent on vesicle size, best explains the amplitude-rise-time correlation, rather than transmitter diffusion time.

Conclusions:

• Fusion pore dynamics, specifically the time course of neurotransmitter release, are a key determinant of mEPSC rise-time and amplitude.
• The amplitude versus rise-time plot serves as a sensitive tool to probe synaptic release properties and the role of fusion pores.
• This study provides novel insights into the biophysics of synaptic vesicle exocytosis and its impact on synaptic signaling.