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!
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
21.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
21.08.2017 | Life Sciences
21.08.2017 | Information Technology
18.08.2017 | Life Sciences