Elevated synaptic vesicle release probability in synaptophysin/gyrin family quadruple knockouts

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Synaptophysins (SYP1, SYP2) and synaptogyrins (SYG1, SYG3) are major synaptic vesicle membrane proteins.
• Their precise physiological functions remain largely unresolved, unlike other well-characterized synaptic vesicle proteins.

Purpose of the Study:

• To investigate the functional role of the synaptophysin and synaptogyrin protein family in regulating neurotransmission.
• To determine the impact of these proteins on vesicle release probability and dynamics.

Main Methods:

• Generation and analysis of knockout mice lacking all four family members (SYP1, SYP2, SYG1, SYG3).
• Electrophysiological recordings at various synapse types to assess neurotransmitter release.
• Quantification of readily releasable vesicle pool size and recruitment timing.

Main Results:

• Robust elevation in the probability of readily releasable vesicle release was observed in knockout mice across multiple synapse types.
• No significant changes were detected in the size of the readily releasable pool or the kinetics of vesicle recruitment.
• These findings indicate that the protein family acts as a negative regulator of neurotransmitter release.

Conclusions:

• Synaptophysins and synaptogyrins function as negative regulators of neurotransmission, dampening synaptic strength.
• They selectively reduce neurotransmitter release at low-frequency firing, suggesting a role in synaptic activity filtering.
• This points to a fundamental role for chemical synapses in biological computation beyond current understanding.