Modeling of the brain vesicles cycle unlocks synaptic secrets

Summary: A new computational model has mapped the cycle of brain vesicles with unprecedented details, providing a new vision of how nerve cells communicate. The researchers collaborated to simulate how vesicles, Tiny Sacs that release neurotransmitters, operate within synapses.

The model reveals how proteins such as Synapsin-1 and Tomasyn-1 regulate the recycling of vesicles, allowing synaptic transmission even at high shot speeds. This advance clarifies a long -standing mystery in neuroscience and opens the door to a better understanding of diseases such as depression and myastenic syndromes.

Key facts:

Bend behavior: only 10-20% of vesicles are active at the same time; The rest are stored in the reserve. New ideas: proteins such as Synapsin-1 and Tomassyn-1 regulate the movement and release of the gallbladder. Medical relevance: the results could help treatments for disorders involving a defective synaptic transmission.

Source: Oist

How do we think, feel, remember or move?

These processes involve synaptic transmission, in which chemical signals are transmitted between nerve cells using molecular containers called vesicles.

Now, researchers have successfully modeled the cycle of vesicles with unprecedented details, revealing new information about the way our brain works.

A joint study, published in Science Advances, among researchers from the Institute of Science and Technology of Okinawa (OIST), Japan and the Medical Center of the Göttingen University (UMG), Germany, has applied a unique computational modeling system, which considers the complicated interaction of vesicles, its cellular environments, activities and interactions, to create a realistic image of the way in which the vesicles in which the vest.

Its model predicts the parameters of synaptic function that could not be proven experimentally in the past, opening new ways in neuroscience research.

“Recent technological advances have allowed experimental scientists to capture increasing amounts of data.

“The challenge now lies in integrating and interpreting all the different types of data, to understand the complexities of the brain,” said Professor Erik of Schutter, head of the Oist Computational Neuroscience Unit and co -author in this study.

“Our model provides a better molecular and spatial detail of the gallbladder cycle, and much faster than any other system before. And it is also transferable to different cells and scenarios. It is a significant jump towards the scientific aspirations of the simulation of full cells and complete tissue.”

“We have been working in synapse for more than 20 years, but some functional steps were difficult to prove experimentally.

“After several years of experimental and computational work adjustment with our Japanese colleagues, we now have a model to test new hypotheses, especially in the context of neurological diseases,” added Professor Silvio Rizzoli, director of the Department of Neuro and Sensory Physiology in the UMG and also co -author in the study.

What is the cycle of synaptic vesicles?

The gallbladder cycle describes the steps through which neurotransmitters (chemical signals) are released in a synapse (a union between nerve cells), to transfer information between cells.

Vesicles containing neurotransmitters move and docked in the membrane, ready to merge and release their contents, before being recycled. The process is driven by electrical stimulation within the brain and is driven by a complex signaling waterfall.

Depending on the situation, different amounts of neurotransmitters must be released during different periods of time. To enable controlled and sustained synaptic transmission, only 10-20% of vesicles are easily available to join at any given time (these are known as the recycling group). Most vesicles are in a reserve pool, immobilized in a cluster.

Many details of this process, including the way in which vesicles move between the reserve and the recycling group, were little known.

The mechanisms of the recycling of high frequency vesicles of stimulation

In their publication, researchers shed new light on the recycling process of vesicles in the hippocampus synapses. With their model, they intended to confirm the behavior of vesicles at experimentally observed frequencies and explore the behavior at higher frequencies.

They discovered that the gallbladder cycle was able to operate at high stimulation frequencies, far beyond what is normally found in nature.

They were also able to identify some of the reasons behind this robust cycle, identifying the roles of the Synap-1 and Tomassyn-1 key proteins in the regulation of vesicles of the group of grouped reserves.

The researchers pointed out that the efficiency of the gallbladder cycle was based on the molecular layer. By physically connecting some vesicles to the membrane with ties, a close supply of vesicles for rapid coupling and the release of neurotransmitters could be made available.

These important findings allow a deeper understanding of the recycling of vesicles, a process involved in many different diseases.

“For example, the release of neurotransmitters is hindered in botulism or some myastenic syndromes. Treatments for depression and other important neurological diseases also often focus on synaptic transmission,” Schutter’s professor explained.

“As we expand our models, potential applications are enormous, both in the development of new therapies and to deepen our fundamental understanding of how the brain works.”

On this neuroscience research news

Author: Tomomi Okubo
Source: Oist
Contact: Tomomi Okubo – Oist
Image: The image is accredited to Neuroscience News

Original research: open access.
“Dynamic regulation of vesicles pools in a detailed space model of the complete synaptic vesicles cycle” by Erik of Schutter et al. Scientific advances

Abstract

Dynamic regulation of groups of vesicles in a detailed space model of the complete synaptic vesicles cycle

The synaptic transmission is driven by a complex cycle of coupling, release and recycling of vesicles, maintained by different vesicles.

However, the partition of vesicles and recruitment of the reserve pool remain little known.

We use a new vesicle modeling technology to model the cycle of unáphic vesicles in unprecedented molecular and spatial details in a hippocampus synapse.

Our model demonstrates a robust recycling of synaptic vesicles that maintain consistent synaptic release, even during high frequency sustained activation.

We also show how Synap-1 cytosolic proteins and volumesyn-1 cooperate to regulate the recruitment of pool reserve vesicles during sustained shot to maintain the transmission, as well as the potential of the adjustment of the active area of ​​selective vesicles to guarantee the rapid relear of the vesicles while minimizing the recruitment of the reserve pool.

We also monitor the use of vesicles in isolated hippocampus neurons using pH sensitive fluorine, which shows that the recruitment of reserve vesicles depends on the firing frequency, even at non -physiologically high shooting frequencies, as predicted by the model.