Acute Complexin Knockout Abates Spontaneous and Evoked Transmitter Release

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• SNARE-mediated synaptic vesicle (SV) fusion regulates neurotransmitter release.
• Complexins are key regulators of SV fusion, but their precise function is debated, with evidence suggesting both facilitatory and inhibitory roles.
• Contradictory findings may stem from different experimental approaches.

Purpose of the Study:

• To elucidate the role of complexins in SV fusion and neurotransmitter release.
• To resolve conflicting data on complexin function by using a stringent genetic perturbation.
• To investigate whether complexins are essential for fusion clamping.

Main Methods:

• Utilized a conditional complexin-knockout mouse line for acute genetic perturbation.
• Examined autaptic and mass-cultured hippocampal neurons.
• Assessed SV fusion probability and neurotransmitter release rates (spontaneous, synchronous, asynchronous, delayed).

Main Results:

• Acute loss of complexins reduced SV fusion probability.
• Neurotransmitter release rates (spontaneous, synchronous, asynchronous, delayed) were diminished upon complexin loss.
• SV priming remained unaffected, and spontaneous SV fusion was not "unclamped."

Conclusions:

• Complexins act as facilitators of SV fusion in mammalian forebrain neurons.
• Complexins are dispensable for the
• fusion clamping
• mechanism in these neurons.