Augmentation controls the fast rebound from depression at excitatory hippocampal synapses

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Calcium Signaling

Background:

• Short-term plasticity involves both positive and negative components, but their interactions are poorly understood.
• Residual calcium (Ca2+) enhances release at low release probability (augmentation), but its role in depression-dominated synapses is unclear.

Purpose of the Study:

• Investigate the impact of residual Ca2+ on neurotransmitter release at excitatory hippocampal synapses under conditions of depression.
• Clarify the mechanisms underlying augmentation and its interaction with synaptic depression.

Main Methods:

• Electrophysiological recordings from hippocampal synapses.
• Analysis of neurotransmitter release dynamics during and after repetitive stimulation.
• Modeling of calcium dynamics and vesicle pool replenishment.

Main Results:

• Residual Ca2+ significantly enhances release at synapses recovering from depression, even with recently recruited vesicles.
• No evidence for vesicle priming or rapid refilling of the readily releasable pool (RRP).
• Augmentation decay correlated with Ca2+ clearance; release probability rebounded quickly but also depressed rapidly.

Conclusions:

• Residual Ca2+ plays a crucial role in modulating release probability during synaptic depression.
• Augmentation can be saturated and occlude other facilitation mechanisms at physiological release conditions.
• Findings help resolve discrepancies in estimating recovery from synaptic depression.