Summary: A new research uncovers molecular mechanisms driving storage formation in the brain, focusing on lush fiber synapses. Researchers observed important proteins, Cav2.1 and Munc13, adjust during storage control, enhancing junction efficiency and power.
Using life mouse brain cells and advanced imaging methods, the crew provided a real-time perspective of memory-linked structural shifts. This research demonstrates how different experiences can be encoded by the hippocampus through synaptic plasticity and neurotransmitters.
The findings provide fresh insights into the chemical foundation of cognitive processes and memory formation. This study provides a chemical foundation for the study of memory-related problems.
Important Information:
- Memory creation involves Cav2.1 and Munc13 protein rearranging at leafy fiber connections.
- The research used “freeze dislocation labeling” to capture chemical changes in life tissue.
- Findings attribute improved junction power, which is crucial for memory encoding, to protein dynamics.
Origin: ISTA
Resembling a seahorse, as its name implies from the Greek words “hippos” ( horse ) and “kampus” ( sea monster ), the hippocampus is a brain region crucial for memory formation. However, until recently, it was difficult for scientists to relate different chemical signals to memory formation.
A team of researchers from the Max Planck Institute for Multidisciplinary Sciences and the Institute of Science and Technology Austria ( ISTA ) are thought to have opened this black box.
Their findings are  , then published , in , PLOS Biology.
Henry Gustav Molaison, known as client ‘ H. M. ‘, was suffering from seizures. Riddled by convulsions, he was referred to a physician, who localized the seizure to the temporal lobes inside his head, home of the brain.
On September 1, 1953, H. M. underwent brain operation, removing his brain to remedy his seizure. After the surgery, the seizure and spasms were gone, but H. M. developed severe side effects.
He was now unable to create new memories because of dopaminergic memory, which prevented him from recalling everything that had happened prior to the surgery. His case helped to explain how storage and function are related to the brain.
Today, the hippocampus is recognized as a critical area in the human brain, engaged in memory formation and geographical navigation. It converts short-term ram into long-term storage, facilitating the correction of individual experience.
In a new study led by Olena Kim, Yuji Okamoto, and , Magdalena Walz Professor for Life Sciences , at the Institute of Science and Technology Austria ( ISTA )  , Peter Jonas, an international team of neuroscientists uncovered new details about the molecular mechanisms that drive memory processing.
The scientists took a precise look at the mossy fiber synapse—a key connection point between specific nerve cells ( neurons ) in the hippocampus—by combining approaches to study its structure, essential molecules, and functionality.
The storage facility
Inside the brain, several types of cells are involved in storage control. Granule cell, for example, are essential for handling incoming information.
Olena Kim, an ISTA grad and current postdoc at the Austrian Academy of Sciences ( AW), explains that “granule cells receive different signals from other brain parts, which they must approach and propagate more.
These indicators get transmitted through the particle cells ‘ axons—their arm-like expansion, known as leafy fibers. The lush fiber synapse, or pyramidal cells, is formed by these fibers.
Neurotransmitters, messenger molecules, facilitate communication at this point, finally triggering the development and storage of memory.
Mossy fibre connections are characterized by their great flexibility, meaning they can change their action, construction, and contacts based on stimuli. This adaptability aids in the hippocampus ‘ ability to distinguish between identical cues and process information effectively.
Kim gives an example,” This presume, you encounter a tiger and a black cat together, both appear dark and feline. One can be distinguished between a lion and a kitty, for example. In the process of encoding and processing these distinctive features, and ultimately obtaining storage and knowledge, mobile fibers synapses play a significant role.
Mossy grain connections in close-up
The precise mechanisms governing the operation of leafy fibre connections ‘ signal processing are still undetermined. In 2020, Peter Jonas, Carolina Borges-Merjane, and Olena Kim set out to study the structure of mossy fiber synapses, by using a new technique called’ Flash and Freeze ‘—a powerful tool, where neurons are frozen right after being stimulated.
” Again then, we were able to relate structural changes in the leafy grain neurons to their functionality”, says Kim.
” But we wanted to expand the scope of the strategy by looking at both the structure of the synapses and the chemical changes that happen when signals are processed.
The scientists were particularly interested in two proteins located at the hormone release area: Cav2.1 magnesium channels, which are important as the flow of magnesium through those channels triggers serotonin release, and Munc13, a key factor, that hints at the neurotransmitter’s readiness to be released.
” Before our research, all the work on these two enzymes was done with biologically fixed mental samples”, Kim continues. As those examples are not dead, they do not offer insights into energetic processes.
” For our fresh study, we were excited to use lived brain tissue to preserve the relationships, the natural works, and the translation of these protein”.
A moon-like surface
With the help of their ISTA colleagues,  , Professor Ryuichi Shigemoto, and , Staff Scientist , Walter Kaufmann, the scientists used the’ freeze fracture labeling ‘ technique.
In mouse brain tissue samples, they chemically activated the memory-forming process by stimulating the granule cells. The brain tissue was then instantly frozen and split into two halves.
The section’s inner side represents the tissue’s exposed surface inside, a 3D footprint of the tissue at that specific time, complete with embedded molecules and proteins.
After labeling Cav2.1 and Munc13 to make them visible, the researchers used an electron microscope to find their exact localization. The images, resembling a close-up of the moon, revealed that upon stimulation, these two proteins rearranged and moved closer together.
Further investigation revealed that the mossy fiber synapse’s functionality is inextricably related to the rearrangement. Peter Jonas summarizes,” Upon activation, there are two changes.
First, the number of vesicles near the membrane increases. Second, there is nano-rearrangement of Cav2.1 and Munc13, making the synapses more powerful and more precise. Both changes may contribute to memory formation”.
The research illuminates how structure and function at a crucial hippocampus synapses. Our memories frequently bring back vivid images. However, so far, we have n’t been able to identify the molecular factors that cause memory formation. The foundation of that is the present study.
Information on animal studies
In order to better understand fundamental processes, for example, in the fields of neuroscience, immunology, or genetics, the use of animals in research is indispensable. No other methods, such as in silico models, can serve as alternative.
The animals are raised, cared for, and treated in accordance with Austrian law’s strict rules. The Austrian Federal Ministry of Education, Science, and Research has a copy of every animal procedure.
About this news about neuroscience research and memory
Author: Andreas Rothe
Source: ISTA
Contact: Andreas Rothe – ISTA
Image: The image is credited to Neuroscience News
Original Research: Open access.
Olena Kim and colleagues ‘” Hippocampal mossy fiber boutons undergo synaptic vesicle reconfiguration and channel-vesicle coupling as a result of a result of a result of a result of a cAMP-PKA-mediated potentiation..” PLOS Biology
Abstract
Hippocampal mossy fiber boutons undergo synaptic vesicle reconfiguration and channel-vesicle coupling as a result of a result of a result of a result of a cAMP-PKA-mediated potentiation.
Synapses ‘ nanoscopic structural changes, which lead to the formation of synaptic engrams, are widely accepted as the cause of information storage in neuronal circuits. However, direct evidence for this hypothesis is lacking.
To test this conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic recordings, and structural analysis by electron microscopy ( EM) and freeze-fracture replica labeling ( FRL ) at the rodent hippocampal mossy fiber synapse, a key synapse in the trisynaptic circuit of the hippocampus.
Synaptic transmission was studied biophysically to determine whether forskolin-induced chemical potentiation increased the size and frequency of readily detectable vesicle pools by 146 % and 49 %, respectively.
The number of vesicles close to the plasma membrane and the number of clusters of the priming protein Munc13-1 increased, indicating an increase in both the number of docked and primed vesicles, according to structural analysis of mossy fiber synapses by EM and FRL.
Furthermore, FRL analysis revealed a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ , channels, suggesting reconfiguration of the channel-vesicle coupling nanotopography.
Our findings demonstrate that active zone structural reorganization is related to presynaptic plasticity. We make the case that synaptic vesicle release site potential organization changes may affect learning and memory at a plastic central synapse.
