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.
Information transmission at the synapse between neurons is a highly complex, but at the same time very fast, series of events. When a voltage change, the so-called action potential, reaches the synaptic terminal in the presynaptic neuron, calcium flows through voltage-gated calcium channels into the presynaptic neuron. This influx leads to a rise in the intracellular calcium concentration. Calcium then binds to a calcium sensor in the presynaptic terminal, which in turn triggers the release of vesicles containing neurotransmitters into the synapse. The released neurotransmitter binds to postsynaptic receptors, leading to a response in the postsynaptic neuron. The coupling between calcium channels and sensors of exocytosis is key in determining the speed, timing and probability of synaptic transmission. Two forms of coupling occur in the brain: in tight, or „nanodomain“ coupling, channels and sensors are located very close to each other, with 10 to 20 nm distance, while in loose, or „microdomain“ coupling, channel and sensor are further apart, in the region of around 100 nm.
Previous research suggests that loose coupling occurs in synapses during early development, while tight coupling is observed in the mature central nervous system. In their current paper, Vyleta and Jonas ask whether, given the advantages of tight coupling – including the speed, temporal precision, fidelity and energy efficiency of synaptic transmission – any synapse in the mature central nervous system makes use of loose coupling? And if it does so, what are the consequences for the function of synaptic transmission?
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.
Oliver Lehmann | EurekAlert!
Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University
Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
17.10.2017 | Life Sciences
17.10.2017 | Life Sciences
17.10.2017 | Earth Sciences