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Presynaptic nanodomains: a tale of two synapses
Lu-Yang Wang1, George J Augustine2
1Program in Neurosciences and Mental Health, SickKids Research Institute Toronto, Canada ; Department of Physiology, University of Toronto Toronto, Canada.
Frontiers in Cellular Neuroscience
|February 13, 2015
Summary
Nanodomain calcium signals, not widespread calcium influx, are crucial for rapid neurotransmitter release at giant synapses. Evidence from squid and mammalian synapses supports this nanodomain hypothesis for synaptic transmission.
Area of Science:
- Neuroscience
- Cell Biology
- Synaptic Physiology
Background:
- Neurotransmitter release is a fundamental process in synaptic transmission.
- Calcium influx through presynaptic voltage-gated calcium channels triggers neurotransmitter release.
- The spatial and temporal dynamics of calcium signaling at synapses remain incompletely understood.
Purpose of the Study:
- To summarize evidence supporting the role of nanodomain calcium signals in neurotransmitter release.
- To investigate nanodomain calcium signaling at the squid giant synapse and the mammalian calyx of Held.
- To elucidate the relationship between calcium channel activity and neurotransmitter release kinetics.
Main Methods:
- Analysis of experimental data from squid giant synapse and mammalian calyx of Held.
- Manipulation of external calcium concentration and presynaptic action potential duration.
- Use of low-affinity calcium indicators, calcium chelators (EGTA, BAPTA), and calcium uncaging.
- Calcium imaging and diffusion simulations at the calyx of Held.
Main Results:
- Non-linear relationship between unitary calcium current and release, versus linear relationship with open channel number at the squid synapse.
- High presynaptic calcium concentrations (hundreds of micromolar) inferred from experiments.
- Differential effects of fast (BAPTA) vs. slow (EGTA) calcium chelators on release.
- Developmental shift from microdomain to nanodomain coupling at the calyx of Held.
- Peak calcium concentrations reaching tens of micromolar at the calyx of Held.
Conclusions:
- Nanodomain calcium signaling is a critical mechanism gating rapid neurotransmitter release.
- The spatial proximity of calcium channels to release sites defines nanodomain signaling.
- Evidence from diverse giant synapse models strongly supports the nanodomain hypothesis.
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