Synaptotagmin 7 Sculpts Short-Term Plasticity at a High Probability Synapse.

Area of Science:

• Neuroscience
• Cellular Neuroscience
• Synaptic Plasticity

Background:

• High release probability (P) synapses typically show short-term depression due to vesicle depletion.
• The prevailing model attributes short-term depression to the depletion of release-ready vesicles post-action potential (AP).
• Layer 4 to layer 2/3 (L4-L2/3) synapses in rodent somatosensory cortex exhibit atypical short-term plasticity, with absent depression at short interstimulus intervals (ISIs).

Purpose of the Study:

• To elucidate the mechanisms underlying the biphasic time course of short-term plasticity at L4-L2/3 synapses.
• To investigate candidate mechanisms including neuromodulation, postsynaptic receptor desensitization, and use-dependent presynaptic calcium changes.
• To determine the role of synaptotagmin 7 (Syt7) in short-term plasticity at this synapse.

Main Methods:

• Whole-cell electrophysiology in acute brain slices from juvenile mice (male and female).
• Two-photon calcium imaging.
• Analysis of synaptic transmission properties across varying interstimulus intervals (ISIs).

Main Results:

• Release probability (P) at single L4-L2/3 synapses varies with ISI, explaining the observed biphasic short-term plasticity.
• A synaptotagmin 7 (Syt7)-dependent mechanism contributes to a transient increase in P at short ISIs.
• Two distinct vesicle release processes were identified: a basal, rapidly depressing mechanism with slow recovery (τ ≈ 3 s) and a Syt7-dependent facilitating mechanism (τ ≈ 100 ms).

Conclusions:

• Short-term plasticity at L4-L2/3 synapses results from the summation of two distinct vesicle release processes.
• The Syt7-dependent mechanism transiently increases release probability after an initial AP, counteracting depletion at short ISIs.
• This dual mechanism allows synapses to maintain high neurotransmission probability across multiple APs within short time frames.