Brain guards remember signals to shape long -term memory

Summary: A new study reveals how calcium ion channels in the brain do not just relate signals – they remember it. Researchers have discovered that CAV2.1 channels with synapses can adopt nearly 200 forms based on electrical activity, effectively entering a “memory state” which weakens signal transmission.

These brief molecular memories accumulate over time, leading to long -term synaptic changes essential to learning and formation of memory. Like a clutch in a car, part of the canal disengages after a repeated activity, preventing an additional signal flow and reshaping communication between neurons.

Key facts:

• Molecular memory: CAV2.1 calcium channels “remember” the previous activity by modifying the shape and temporarily blocking the signal flow.
• Synaptic plasticity link: The short -term channel memory is piling up, resulting in long -term synaptic changes.
• Medicines targeting potential: The study identifies specific parts of the channel which could be targeted to treat neurological disorders.

Source: Link university

One of the superpowers of the brain is his ability to learn past experiences and to train memories. These vital processes depend on the reshaping of connections between neurons in the brain.

The nerve junctions, called synapses, are reinforced or weakened throughout life in such a way that the brain is, in a certain sense, in constant evolution at the cellular level.

This phenomenon is called synaptic plasticity.

Several processes contribute to synaptic plasticity in the nervous system. One of these processes has to do with a type of molecules called calcium ion channels, which have long been interested in researchers from the University of Linköping (Liu).

“I want to discover the secret life of these molecules of ionic canals.

But beyond that, these molecules also have a kind of memory and remember the previous nervous signals, “explains Antonios Pantazi, associate professor in the Department of Biomedical and Clinical Sciences of Liu, who led the study.

The objective of this study was on a specific type of ion channel, the CAV2.1 channel, which is the most common calcium ion channel in the brain. The ion canal is located at Synapse, at the very end of the neuron.

When an electrical signal goes through the neuron, the ion channel opens, setting in motion a process leading to the release of neurotransmitter to the receiver neuron in the synapse. In this way, the CAV2.1 channels are the guards of synaptic communication, neuron-neuron.

The prolonged electrical activity reduces the number of CAV2.1 channels which can open, resulting in a less issuing release, so that the receiver neuron receives a lower message.

It is as if the channels could “remember” the previous signaling and, in so doing, go to the opening by subsequent signals. The way it works at the molecular level is unknown to scientists so far.

Linköping researchers have now discovered a mechanism on how the ion canal can “remember”. The canal is a large molecule made up of several interconnected parts, which can move compared to others in response to electrical signals.

They discovered that the ion canal can take nearly 200 different forms depending on the resistance and duration of an electrical signal; It is a very complex molecular machine.

“We believe that when the sustained electric nerve is signed, an important part of the molecule is disconnected from the channel door, similar to the way the clutch in a car breaks the connection between the engine and the wheels.

“The ion canal can no longer be opened. When hundreds of signals occur over a long enough time, they can convert most of the channels into this “storage state of memory” for several seconds, “said Antonios Pantazi.

If the ion canal can “remember” a few seconds, how does it contribute to learning throughout life? This type of collective memory in ion channels can accumulate over time and reduce communication between two neurons.

This then leads to changes in the receiver neuron, lasts hours or days. Finally, it results in much longer changes in the brain, such as the elimination of weakened synapses.

“In this way, a” memory “which lasts a few seconds in a single molecule can make a small contribution to the memory of a person who lasts a lifetime,” explains Antonios Pantazi.

Increased knowledge of the functioning of these ionic calcium channels can contribute to the treatment of certain diseases in the long term. There are many variants of the gene that produce the CAV2.1, CACNA1A channel, which are linked to rare but serious neurological diseases, which often take place in families.

To develop drugs against them, it is useful to know which part of the large ion channel you want to affect and how its activity should be modified.

“Our work indicates in which part of the protein should be targeted when developing new drugs,” said Antonios Pantazis.

Funding: Research was funded by the Swedish Research Council, the Center for Molecular Medicine at Linköping University, the Swedish Brain Foundation, the Swedish Heart-Lung Foundation, the Lions Research Fund for Public Diseases and the NIH.

About these news of the search for neuroscience and memory

Author: Pantazi Antonios
Source: Link university
Contact: Antonios Pantazis – Linkoping University
Picture: The image is credited with Neuroscience News

Original search: Open access.
“A rich conformational palette underlies the human turnover_V2.1-Canal availability »by Antonios Pantazis et al. Nature communications

Abstract

A rich conformational palette underlies the human turnover_VAvailability of 2.1 channels

Opening mentioned by the depolarization of CA_V2.1 (type P / q) CA²⁺-The channels trigger the release of neurotransmitters, while inactivation dependent on tension (VDI) limits the availability of the channel to open, contributing to synaptic plasticity.

The CA mechanism_V2.1 The response to the tension is not clear.

Using fluorometry and kinetic voltage-harp modeling, we follow optically and physically characterize the structural dynamics of the four Ca_V2.1 Domains of tension sensors (VSD). VSDs are differently sensitive to tension changes, both brief and long lifespan.

VSD-I seems to drive the opening directly and convert between two function modes, associated with VDI. VSD-II is apparently insensitive to tension.

VSD-III and VSD-IV feel more negative tensions and undergo a conversion dependent on unrealed tension with VDI. Auxiliary β subunits regulate the VSD-I-Pore coupling and the VSD conversion kinetics.

Therefore, the central role of CA_V2.1 Channels in synaptic release, and their contribution to plasticity, memory formation and learning, can come from conformional changes dependent on VSD-I.