Paired-pulse plasticity at the single release site level: an experimental and computational study

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Computational Neuroscience

Background:

• CA3-CA1 glutamatergic synapses in the hippocampus display significant heterogeneity in release probability and paired-pulse (PP) plasticity.
• This heterogeneity is established early in the neonatal period, even when connections have a single release site.

Purpose of the Study:

• To investigate the relative importance of different factors contributing to the heterogeneity in PP plasticity at CA3-CA1 synapses.
• To understand the mechanisms underlying variations in synaptic strength and plasticity.

Main Methods:

• Utilized a computational model based on data from single neonatal CA3-CA1 synapses.
• Analyzed the impact of vesicle pool size, initial release probability (P(ves1)), and changes in release probability (P(ves)) on PP plasticity.

Main Results:

• At a 20 msec PP interval, the PP ratio varied widely (0.1 to 4.5), with desensitization and replenishment playing minor roles.
• Heterogeneity in PP plasticity was primarily explained by variations in P(ves1), with the preprimed pool size being less significant.
• Changes in release probability from the first to the second stimulus (P(ves2)) were uniform, contributing little to the observed PP ratio heterogeneity.

Conclusions:

• Initial release probability (P(ves1)) is the main driver of heterogeneity in PP plasticity at neonatal CA3-CA1 synapses.
• The relationship between release probability alterations and PP ratio is complex and depends on initial conditions and the specific factor altered.
• Synaptic strength regulation involves intricate interplay between vesicle pool dynamics and release probability modulation.