Central cholinergic synaptic vesicle loading obeys the set-point model in Drosophila

Area of Science:

• Neuroscience
• Molecular Biology
• Synaptic Transmission

Background:

• Neurotransmitter release is regulated by synaptic vesicle (SV) content and release probability.
• The vesicular acetylcholine transporter (VAChT) is crucial for acetylcholine loading into SVs at cholinergic synapses.

Purpose of the Study:

• To investigate the role of VAChT in regulating SV content and release frequency at central synapses in Drosophila melanogaster.
• To determine if cholinergic SV loading follows a "set-point" or "steady-state" model.

Main Methods:

• Utilized an insecticidal compound (5Cl-CASPP) to inhibit VAChT activity.
• Employed transgenic overexpression of VAChT in cholinergic interneurons.
• Analyzed spontaneous SV release, quantal size, and vesicle number at the active zone.

Main Results:

• Decreased VAChT activity reduced spontaneous SV release without altering quantal size or vesicle number, suggesting neurotransmitter undersupply.
• VAChT overexpression increased SV release frequency, again without changes to quantal size or vesicle number.
• A VAChT polymorphism lacking a glutamine residue increased spontaneous SV release and quantal size.

Conclusions:

• Central cholinergic SV loading in Drosophila adheres to the "set-point" model.
• The poly-glutamine domain of VAChT may function in sensing neurotransmitter levels within SVs.