Ca2+ buffer saturation underlies paired pulse facilitation in calbindin-D28k-containing terminals

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Calcium Signaling

Background:

• Paired pulse facilitation (PPF) is a short-term synaptic plasticity phenomenon.
• Calcium (Ca2+) buffer saturation has been hypothesized as a mechanism for PPF.
• The role of endogenous Ca2+ buffers in PPF under physiological conditions remains largely uncharacterized.

Purpose of the Study:

• To investigate whether endogenous fast calcium buffer saturation contributes to PPF at native synapses.
• To elucidate the role of calbindin-D28k (CB) in PPF in the mouse neocortex.
• To determine the underlying mechanisms of PPF in CB-containing synapses.

Main Methods:

• Paired recordings from synaptically connected interneurons and pyramidal neurons in mouse neocortex.
• Presynaptic terminal dialysis with BAPTA or CB.
• Experiments involving CB knockout mice.
• Manipulation of extracellular Ca2+ concentrations and use of EGTA.

Main Results:

• Dialysis of presynaptic terminals increased the first response amplitude and decreased PPF.
• Loading terminals with BAPTA or CB rescued the effects of CB washout.
• PPF in CB-containing terminals was dependent on Ca2+ influx, not initial release probability.
• CB knockout mice confirmed buffer saturation as a key mechanism for PPF.

Conclusions:

• Saturation of the endogenous fast Ca2+ buffer calbindin-D28k (CB) is a major determinant of PPF at CB-containing synapses.
• This mechanism provides a novel way for presynaptic activity to control synaptic gain.
• The findings highlight the importance of endogenous calcium buffering in regulating synaptic transmission.