Synaptotagmin 7 Mediates Both Facilitation and Asynchronous Release at Granule Cell Synapses

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Calcium Signaling

Background:

• Presynaptic action potentials evoke calcium influx, leading to vesicle fusion and neurotransmitter release.
• Residual calcium (Ca_res) influences subsequent synaptic events like facilitation and asynchronous release (AR).
• Synaptotagmin 7 (Syt7) has been implicated in facilitation and AR, but its dual role at the same synapse is unclear.

Purpose of the Study:

• To investigate the role of synaptotagmin 7 (Syt7) in mediating synaptic facilitation and asynchronous release (AR) at cerebellar granule cell synapses.
• To determine if Syt7 can mediate both AR and facilitation, despite their distinct properties.
• To assess the contribution of Syt7 to these phenomena in mice.

Main Methods:

• Utilized Syt7 knock-out (KO) and wild-type (WT) mice.
• Examined cerebellar granule cell synapses onto stellate and Purkinje cells.
• Measured synaptic facilitation and asynchronous release (AR) following presynaptic activity.
• Assessed initial release probability and Ca_res signals.

Main Results:

• Syt7 deficiency reduced both facilitation and AR duration and amplitude compared to WT.
• Initial release probability and Ca_res signals remained unchanged in Syt7 KO animals.
• Syt7 was identified as the primary mediator of both facilitation and AR at these synapses, despite their differing calcium sensitivities.

Conclusions:

• Synaptotagmin 7 (Syt7) plays a crucial role in mediating both synaptic facilitation and asynchronous release (AR) at cerebellar granule cell synapses.
• While Syt7-independent mechanisms contribute, Syt7 is the dominant factor for both phenomena.
• This finding unifies the understanding of Syt7's function in synaptic plasticity.