Presynaptic endoplasmic reticulum regulates short-term plasticity in hippocampal synapses

Area of Science:

• Neuroscience
• Computational Biology
• Synaptic Plasticity

Background:

• Short-term plasticity (STP) modulates synaptic transmission based on recent activity.
• Presynaptic calcium dynamics, primarily from voltage-dependent calcium channels, regulate STP.
• Endoplasmic reticulum (ER) calcium stores are present in presynaptic terminals but their role in STP is unknown.

Purpose of the Study:

• To investigate the contribution of presynaptic ER calcium stores to STP at CA3-CA1 synapses.
• To model the role of ER in synaptic function using realistic synaptic geometries.

Main Methods:

• In-silico experiments using computational models.
• Simulations based on reconstructed rat CA3-CA1 synapse geometries.

Main Results:

• Presynaptic ER is critical for the characteristic STP profile of CA3-CA1 synapses.
• ER calcium stores enhance the reliability of synapses with low release probability.
• Blocking ER calcium release reduces synaptic facilitation, mimicking observations in Alzheimer's disease models.

Conclusions:

• Presynaptic ER plays a vital role in regulating normal short-term synaptic plasticity.
• ER calcium stores are essential for reliable synaptic function.
• Dysfunction of presynaptic ER may contribute to neurological disorders like Alzheimer's disease.