Research conducted by the Computational Neuroscience Unit at the Okinawa Institute of Science and Technology Graduate University (OIST) has shown for the first time that a computer model can replicate and explain a unique property displayed by a crucial brain cell. Their findings, published today in eLife, shed light on how groups of neurons can self-organize by synchronizing when they fire fast.

The model focuses on Purkinje neurons, which are found within the cerebellum. This dense region of the hindbrain receives inputs from the body and other areas of the brain in order to fine-tune the accuracy and timing of movement, among other tasks.

“Purkinje cells are an attractive target for computational modeling as there has always been a lot of experimental data to draw from,” said Professor Erik De Schutter, who leads the Computation Neuroscience Unit. “But a few years ago, experimental research into these neurons uncovered a strange behavior that couldn’t be replicated in any existing models.”

These studies showed that the firing rate of a Purkinje neuron affected how it reacted to signals fired from other neighboring neurons. {module INSIDE STORY}

The rate at which a neuron fires electrical signals is one of the most crucial means of transmitting information to other neurons. Spikes, or action potentials, follow an “all or nothing” principle – either they occur, or they don’t – but the size of the electrical signal never changes, only the frequency. The stronger the input to a neuron, the quicker that neuron fires.

But neurons don’t fire in an independent manner.  “Neurons are connected and entangled with many other neurons that are also transmitting electrical signals. These spikes can perturb neighboring neurons through synaptic connections and alter their firing pattern,” explained Prof. De Schutter.

Interestingly, when a Purkinje cell fires slowly, spikes from connected cells have little effect on the neuron’s spiking. But, when the firing rate is high, the impact of input spikes grows and makes the Purkinje cell fire earlier.

“The existing models could not replicate this behavior and therefore could not explain why this happened. Although the models were good at mimicking spikes, they lacked data about how the neurons acted in the intervals between spikes,” Prof. De Schutter said. “It was clear that a newer model including more data was needed.”

Testing a new model

Fortunately, Prof. De Schutter’s unit had just finished developing an updated model, an immense task primarily undertaken by now former postdoctoral researcher, Dr. Yunliang Zang.

Once completed, the team found that for the first time, the new model was able to replicate the unique firing-rate dependent behavior.

In the model, they saw that in the interval between spikes, the Purkinje neuron’s membrane voltage in slowly firing neurons was much lower than the rapidly firing ones.

Cell membranes have a voltage across them due to the uneven distribution of charged particles, called ions, between the inside and outside of the cell. Neurons can shuttle ions across their membrane through channels and pumps, which changes the voltage of the membrane. Fast firing Purkinje neurons have a higher membrane voltage than slow firing neurons.

Credit: 

Image modified from "How neurons communicate: Figure 2," by OpenStax College, Biology (CC BY 4.0).

“In order to trigger a new spike, the membrane voltage has to be high enough to reach a threshold. When the neurons fire at a high rate, their higher membrane voltage makes it easier for perturbing inputs, which slightly increase the membrane voltage, to cross this threshold and cause a new spike,” explained Prof. De Schutter.

The researchers found that these differences in the membrane voltage between fast and slow firing neurons were because of the specific types of potassium ion channels in Purkinje neurons.

“The previous models were developed with only the generic types of potassium channels that we knew about. But the new model is much more detailed and complex, including data about many Purkinje cell-specific types of potassium channels. So that’s why this unique behavior could finally be replicated and understood,” said Prof. De Schutter.

The key to synchronization

The researchers then decided to use their model to explore the effects of this behavior on a larger-scale, across a network of Purkinje neurons. They found that at high firing rates, the neurons started to loosely synchronize and fire together at the same time. Then when the firing rate slowed down, this coordination was quickly lost.

Using a simpler, mathematical model, Dr. Sungho Hong, a group leader in the unit, then confirmed this link was due to the difference in how fast and slow firing Purkinje neurons responded to spikes from connected neurons.

“This makes intuitive sense,” said Prof. De Schutter. He explained that for neurons to be able to sync up, they need to be able to adapt their firing rate in response to inputs to the cerebellum. “So this syncing with other spikes only occurs when Purkinje neurons are firing rapidly,” he added.

When a group of Purkinje neurons fire rapidly, loose synchronization occurs. This can be seen by the spikes occurring in groups at regular intervals (highlighted in yellow). When Purkinje neurons fire slowly, this synchronization does not occur.

The role of synchrony is still controversial in neuroscience, with its exact function remaining poorly understood. But many researchers believe that synchronization of neural activity plays a role in cognitive processes, allowing communication between distant regions of the brain. For Purkinje neurons, they allow strong and timely signals to be sent out, which experimental studies have suggested could be important for initiating movement.

“This is the first time that research has explored whether the rate at which neurons fire affects their ability to synchronize and explains how these assemblies of synchronized neurons quickly appear and disappear,” said Prof. De Schutter. “We may find that other circuits in the brain also rely on this rate-dependent mechanism.”

The team now plans to continue using the model to probe deeper into how these brain cells function, both individually and as a network. And, as technology develops and supercomputing power strengthens, Prof. De Schutter has an ultimate life ambition.

“My goal is to build the most complex and realistic model of a neuron possible,” said Prof. De Schutter. “OIST has the resources and supercomputing power to do that, to carry out really fun science that pushes the boundary of what’s possible. Only by delving into deeper and deeper detail in neurons, can we really start to better understand what’s going on.”

Pioneering new research has revealed the first direct evidence that groups of stars can tear apart their planet-forming disc, leaving it warped and with tilted rings.

An international team of experts, led by astronomers at the University of Exeter, has identified a stellar system where planet formation might take place in inclined dust and gas rings within a warped circumstellar disc around multiple stars.

A view from a potential planet around this system will give the observer a stunning view of a tilted, multiple stellar constellation - similar to Star Wars' Tatooine.

The results were made possible thanks to observations with the European Southern Observatory's Very Large Telescope (VLT), Georgia State University's Center for High-Angular Resolution Astronomy telescope array (CHARA), and the Atacama Large Millimeter/submillimeter Array (ALMA).

The research is the first output of a large programme on young stellar system that uses a pioneering infrared imager, called MIRC-X, that combines the light from all six telescopes of the CHARA telescope array. MIRC-X has been built by the Universities of Michigan and Exeter as part of a European Research Council-funded research project.

The instrument has been designed to give new insights into how star and planet formation is taking place within the rotating, circumstellar discs of dense dust and gas surrounding young stars.

Our Solar System is remarkably flat, with the planets all orbiting in the same plane. However, this is not always the case, especially for planet-forming discs around multiple stars, like the object of the new study: GW Orionis. This system, located just 1,200 light-years away in the constellation of Orion, has three stars and a deformed, broken-apart disc surrounding them.

Stefan Kraus, professor of astrophysics at the University of Exeter, who led the research published today in Science, said: "We're really excited that our new MIRC-X imager has provided the sharpest view yet of this intriguing system and revealed the gravitational dance of the three stars in the system. Normally, planets form around a flat disc of swirling dust and gas- yet our images reveal an extreme case where the disc is not flat at all.", said Stefan Kraus,

"Instead it is warped and has a misaligned ring that has broken away from the disc. The misaligned ring is located in the inner part of the disc, close to the three stars. The effect is that the view of a potential planet within this ring looks remarkably like that of Tatooine, of Star Wars fame." {module INSIDE STORY}

The team observed the system with the SPHERE instrument on ESO's VLT and with ALMA, and were able to image the inner ring and confirm its misalignment. The team observed shadows that this ring casts on the rest of the disc. This helped them figure out the 3D shape of the rings and overall disc geometry.

The new research reveals that this inner ring contains 30 Earth masses of dust, which could be enough to form planets.

Alexander Kreplin of the University of Exeter, said: "Any planets formed within the misaligned ring will orbit the star on highly oblique orbits and we predict that many planets on oblique, wide-separation orbits will be discovered in future planet imaging surveys.

"Since more than half of stars in the sky are born with one or more companions, this raises an exciting prospect: there could be an unknown population of exoplanets that orbit their stars on very inclined and distant orbits."

To reach these conclusions, the team observed GW Orionis for over 11 years and mapped the orbit of the stars with unprecedented precision. Alison Young, a member of the team from the Universities of Exeter and Leicester, said: "We found that the three stars do not orbit in the same plane, but their orbits are misaligned with respect to each other and with respect to the disc."

The international team, with researchers from the UK, Belgium, Chile, France and the US, then combined their exhaustive observations with supercomputer simulations to understand what had happened to the system. For the first time, they were able to clearly link the observed misalignments to the theoretical 'disc-tearing effect', which suggests that the conflicting gravitational pull of stars in different planes can warp and break their surrounding disc.

"We conducted simulations that show that the misalignment in the orbits of the three stars could cause the disc around them to break into distinct rings. This is what we see in the observations.", said Matthew Bate, professor of theoretical astrophysics at Exeter, who carried out some of the supercomputer simulations on the system. "The observed shape of the inner ring also matches predictions on how the disc would tear."