Spontaneous and evoked synaptic vesicle release arises from a single releasable pool

Area of Science:

• Neuroscience
• Cell Biology
• Synaptic Transmission

Background:

• Quantal content calculation assumes shared vesicle pools for spontaneous and evoked release.
• This assumption is challenged by theories proposing distinct vesicle pools for different release modes.

Purpose of the Study:

• To investigate whether spontaneous and evoked neurotransmitter release utilize the same or different synaptic vesicle pools.
• To determine the reversibility and cross-depletion dynamics between spontaneous and evoked release modes.

Main Methods:

• Pharmacological alkalinization was used to "silence" synaptic vesicles.
• Optogenetic acidification was employed to rescue vesicle function.
• Fluorescent tagging of Vti1a and CRISPR-Cas9 gene editing were used to track vesicle trafficking.

Main Results:

• Silenced synaptic vesicles, when rescued during evoked or spontaneous activity, cross-depleted the complementary release mode.
• This cross-depletion effect was fully reversible.
• Endogenous tagging of Vti1a did not show significant trafficking to synaptic vesicles, unlike overexpression.

Conclusions:

• Both spontaneous and evoked neurotransmitter release draw synaptic vesicles from the same readily releasable pool.
• The findings challenge the concept of distinct vesicle pools for spontaneous and evoked release.
• Synaptic vesicle recycling and release mechanisms are more integrated than previously thought.