SynapShot Unveiled: Observing the Processes of Memory and Cognition in Real Time

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A research team developed SynapShot, a novel technique for real-time observation of synapse formation and alterations. This breakthrough, allowing live monitoring of synaptic changes in neurons, is expected to transform neurological research and enhance understanding of brain functions. Credit:

SynapShot, developed by an international research team, marks a major advancement in neuroscience by enabling real-time, live observation of synaptic changes in the brain.

The human brain contains approximately 86 billion neurons and 600 trillion synapses that exchange signals between the neurons to help us control the various functions of the brain including cognition, emotion, and memory. Interestingly, the number of synapses decrease with age or as a result of diseases like Alzheimer’s, and research on synapses thus attracts a lot of attention. However, limitations have existed in observing the dynamics of synapse structures in real-time.

Observing Dynamically Changing Synapses

Figure 1. To observe dynamically changing synapses, dimerization-dependent fluorescent protein (ddFP) was expressed to observe flourescent signals upon synapse formation as ddFP enables fluorescence detection through reversible binding to pre- and postsynaptic terminals. Credit: KAIST Optogenetics & RNA therapeutics Lab

Breakthrough in Synapse Observation

On January 8, a joint research team led by Professor Won Do Heo from the KAIST Department of Biological Sciences, Professor Hyung-Bae Kwon from Johns Hopkins School of Medicine, and Professor Sangkyu Lee from the Institute for Basic Science (IBS) revealed that they have developed the world’s first technique to allow real-time observation of synapse formation, extinction, and alterations.

Professor Heo’s team conjugated dimerization-dependent fluorescent proteins (ddFP) to synapses in order to observe the process in which synapses create connections between neurons in real-time. The team named this technique SynapShot, by combining the words ‘synapse’ and snapshot’, and successfully tracked and observed the live formation and extinction processes of synapses as well as their dynamic changes.

Changes of the Flourescence of the Synapse Sensor (SynapShot)

Figure 2. Microscopic photos observed through changes of the flourescence of the synapse sensor (SynapShot) by cultivating the neurons of an experimental rat and expressing the SynapShot. The changes in the synapse that is created when the pre- and post-synaptic terminals come into contact and the synapse that disappears after a certain period of time are measured by the fluorescence of the SynapShot. Credit: KAIST Optogenetics & RNA therapeutics Lab

Enhancements and Applications of SynapShot

Through a joint research project, the teams led by Professor Heo and Professor Sangkyu Lee at IBS together designed a SynapShot with green and red fluorescence, and were able to easily distinguish the synapse connecting two different neurons. Additionally, by combining an optogenetic technique that can control the function of a molecule using light, the team was able to observe the changes in the synapses while simultaneously inducing certain functions of the neurons using light.

Simultaneous Use of Green-SynapShot and Red-SynapShot

Figure 3. Simultaneous use of green-SynapShot and red-SynapShot to distinguish and observe synapses with one post-terminal and different pre-terminals. Credit: KAIST Optogenetics & RNA therapeutics Lab

Through more joint research with the team led by Professor Hyung-Bae Kwon at the Johns Hopkins School of Medicine, Professor Heo’s team induced several situations on live mice, including visual discrimination training, exercise, and anesthesia, and used SynapShot to observe the changes in the synapses during each situation in real-time. The observations revealed that each synapse could change fairly quickly and dynamically. This was the first-ever case in which the changes in synapses were observed in a live mammal.

Strengthening of Synaptic Connections Through Signals of Brain-Derived Neurotrophic Factor Is Observed

Figure 4. Dimer-dependent fluorescent protein (ddFP) exists as a green fluorescent protein as well as a red fluorescent protein, and can be applied together with blue light-activated optogenetic technology. After activating Tropomyosin receptor kinase B (TrkB) by blue light using optogenetic technology, the strengthening of synaptic connections through signals of brain-derived neurotrophic factor is observed using red-SynapShot. Credit: KAIST Optogenetics & RNA therapeutics Lab

Conclusion and Future Prospects

Professor Heo said, “Our group developed SynapShot through a collaboration with domestic and international research teams, and have opened up the possibility for first-hand live observations of the quick and dynamic changes of synapses, which was previously difficult to do. We expect this technique to revolutionize research methodology in the neurological field, and play an important role in brightening the future of brain science.”

Real-Time Changing Synapses in the Visual Cortex

Figure 5. Micrographs showing real-time changing synapses in the visual cortex of mice trained through visual training using in vivo imaging techniques such as two-photon microscopy as well as at the cellular level. Credit: KAIST Optogenetics & RNA therapeutics Lab

This research, conducted by co-first authors Seungkyu Son (Ph.D. candidate), Jinsu Lee (Ph.D. candidate), and Dr. Kanghoon Jung from Johns Hopkins, was published in the online edition of Nature Methods on January 8 under the title “Real-time visualization of structural dynamics of synapses in live cells in vivo”, and will be printed in the February volume.

Reference: “Real-time visualization of structural dynamics of synapses in live cells in vivo” by Seungkyu Son, Kenichiro Nagahama, Jinsu Lee, Kanghoon Jung, Chuljung Kwak, Jihoon Kim, Young Woo Noh, Eunjoon Kim, Sangkyu Lee, Hyung-Bae Kwon and Won Do Heo, 8 January 2024, Nature Methods.
DOI: 10.1038/s41592-023-02122-4

This research was supported by Mid-Sized Research Funds and the Singularity Project from KAIST,  and by IBS.

3 Comments on "SynapShot Unveiled: Observing the Processes of Memory and Cognition in Real Time"

  1. kesiriy doctormehrdad | January 21, 2024 at 10:44 am | Reply

    Hello, don’t be tired.How did the souls of the spirits become the souls of the Lord?Those who, millions of years ago, had their skulls pierced with a stone, a more perfect soul would come out of their brains due to the opening of their skulls.If the skulls of those who die are removed and they Put them in special coffins and a bigger genie will come out of their corpses.Genie is the two letters of war, genin, crime, madness, gendar, and warrior in the south of heaven.The word genie in Farsi means the ghost of a human being.Now, when I translate and send to you in Latin America, the language will change when it is translated into English, and by sending synonyms, I want to make the English-speaking audience aware of words that are synonyms and are of the same familyand similar to each other.I want to make Razi understand you in the words I sent you, such as genie, war, madness, crime, but unfortunately, this cannot be achieved because the words genie, madness, genie, crime, war, paradise in Farsi, all thesewords are of the same family and synonyms, but when they are translated, they create a whole community that I sent it, everything gets ruined during the translation.The words jinn, war, madness, crime, and heaven are not the same family.Therefore, we come to the conclusion that the Quran cannot be the book of all Muslims and be used for all Muslims in the world, because the words change, that’s why.Islam has infiltrated the culture of every nation, war, madness and crime have occurred in Farsi, there are two letters of gen in the word war, but the word war, which is translated into English, does not become GANG.I typed the words jen and geng in Farsi, the two alphabets are the same, but in English the word war is war, but in Farsi the word changes, it changes in English, and when translating the text that I sent, the words jenand war are not synonymous, that’s why God in Surah Chahar Abraham said, “We did not send a messenger to any nation unless it spoke the same language as that nation, and God and the Lord send a messenger from the same nation. Whenever Islamwas in a land, there was a war where the religion and the Qur’an of the Salamis spoke the same language as the people of the land that the Salamis conquered.”They decided that the war will not end as long as the instructions of the Qur’an and Islam are in that non-Islamic land, because they and the lords of that land have been violated and do not want the instructions of the Islamic Qur’an to be used there, which is not the same language as the Qur’an of those Arabs.For other ethnic groups, the cause of wars is also because of language, and in this gengha gen plays a role, that’s why the two or three letters jen jn are synonymous with the word geng, it is synonymous with the word war.time in iran 10:14

    • kesiriy doctormehrdad | January 22, 2024 at 12:43 am | Reply

      With regards and courtesy to the people of the above topic, last night my humble servant explained that all or most of the Muslim wars were because of language, and in these wars jinn played a role.The great spirits of the world were both Arabs and Persians.I was afraid of the Arabs because of their bad religion and religion, and the Arabs followed the instructions of the Qur’an.I did not like the Arabs because of this, but now my position and vision have changed.And I became fully aware of this issue that I raised and I realized the secret that the reason why the jinns caused the war of war was that there are two letters of jinn in the first two letters of war.

      • kesiriy doctormehrdad | January 22, 2024 at 1:11 am | Reply

        But in Farsi, there are two letters of gen in the word war, but in English, there are no two letters of gen in war.English in Persian grammar, the word madness in Farsi has two letters jinn in the word jinn, again in the word crime there are two letters jinn.And it can guide madness and crime by focusing on specific people over whom jinns dominate, in fact, God and the lords of the world are also the jinn, and I am 100% aware of this, and I am protected by God and the lordsof the world.He has appointed his time, savior, and vicegerent to put aside the religions that have caused war, madness, conflict, and crime, and to follow God’s orders.I am knowledgeable in all legal, social, scientific, political, religious, and religious matters.It is necessary that if God has chosen me, then He has revealed all the secrets of creation to me and made me aware of their nature.does not find

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