February 7, 2014
Loose Coupling Between Calcium Channels And Sensors: A Key Mechanism Underlying Synaptic Plasticity
Science paper by IST Austria scientists reports first evidence for “microdomain” coupling at a mature central synapse and explores the implications for synaptic plasticity
In research published in this week’s online edition of Science (DOI: 10.1126/science.1244811), postdoc Nicholas Vyleta and Professor Peter Jonas of the Institute of Science and Technology Austria (IST Austria) uncover the existence of loose coupling between calcium channels and release sensors of exocytosis at a mature central synapse in the rodent brain. The researchers show that loose coupling provides a framework for presynaptic plasticity, a hallmark of synaptic signaling in hippocampal microcircuits.
A specific synapse in the hippocampus, the mossy fiber synapse on CA3 pyramidal neurons, which is accessible to direct recording using the patch-clamp method and shows a high degree of plasticity, was the focus in this research. To investigate whether loose or tight coupling occurs in this synapse, Vyleta and Jonas made use of calcium chelators, which capture calcium ions on their way from the source to the sensor, to investigate the timescale and distance of coupling. If only the fast-acting chelator, BAPTA, can inhibit exocytosis and synaptic transmission, but the slow chelator EGTA cannot, tight coupling is at work, while in loose coupling, both fast and slow chelators can inhibit transmission. As both fast and slow chelators suppress transmission in the synapse under investigation, results suggest loose coupling between channels and sensors, with a mean coupling distance of around 75 nm.
Why does loose coupling, which is likely slower and has less fidelity than tight coupling, exist in the mossy fiber-pyramidal neuron synapse? Further results by Vyleta and Jonas show that due to loose coupling, fast endogenous calcium buffers in the synapse can act as a brake on transmission, controlling how likely the initial release of neurotransmitter is. Loose coupling provides the time frame for endogenous buffers to act on synaptic transmission. The saturation of endogenous buffers after repeated stimulation may also promote facilitation, the phenomenon in which impulses are more likely to generate action potentials when they closely follow a prior impulse.
The new findings challenge the view that loose coupling is a developmental phenomenon, demonstrating instead that coupling is regulated in a synapse-specific way. Loose coupling is predominantly used at dynamic and plastic synapses, both in the developing and the mature brain. Together with fast endogenous calcium buffers, loose channel-sensor coupling may provide the molecular framework for presynaptic plasticity, a hallmark of hippocampal neurons.
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