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Editor-in-Chief | Introduction to the award-winning research of Enzymic Science-PINS: Neuromodulation Candidate Award: Yang Weijian, Assistant Professor at the University of California, Davis (UC Davis)
.
Graduated from the Department of Electronics of Peking University in 2008; received a Ph.
D.
from the Department of Electronics at UC Berkeley in 2013; worked as a postdoctoral fellow in the Department of Biology at Columbia University from 2014 to 2017; joined at the end of 2017 Department of Electronic and Computer Engineering, University of California, Davis
.
He is currently engaged in the interdisciplinary research of electronic engineering and neuroscience, mainly developing advanced optical systems and neural technologies, and using them to monitor and control the activities of neural circuits, so as to gain insight into the organization and operation mechanism of neural circuits and nerves.
How the activity promotes animal behavior
.
Perception and behavior stem from the coordinated activities between neurons in the brain's neural circuits
.
Multiple interconnected neurons form a neuron group and become the unit that drives the complex functions of the brain
.
The precise regulation of neuronal group activity helps to analyze neural circuits and study the causal relationship between neural activity and animal behavior
.
It is also expected to play an important role in the treatment of brain diseases and become a new tool for precision medicine
.
Electrical stimulation is the most mature method of regulating brain activity
.
However, penetrating electrodes are highly invasive and lack cell-level resolution
.
All neurons near the electrode will be stimulated indiscriminately, which may cause off-target effects
.
This not only limits the application of electrical stimulation in the study of neural circuits and clinical treatment, but also may produce side effects in the latter
.
Optogenetics is a new method of regulating neural activity
.
Compared with electrical stimulation, optogenetics can act on specific cell types, but its early application in the living brain faces the same problem as electrical stimulation: incident light irradiates a large brain area, and many neurons will be destroyed.
Stimulate differently
.
Two-photon light solves the problem of spatial resolution
.
Borrowing laser scanning microscope technology, two-photon light can stimulate a single neuron in sequence
.
However, stimulating single cells sequentially cannot simulate the simultaneous activity of multiple neurons in the brain
.
To use an analogy, stimulating neurons is similar to playing the piano
.
Stimulating a single neuron at a time is like playing the piano with one finger, and it cannot produce rhythmic and melody music
.
In order to effectively regulate neural activity, we need to stimulate a group of neurons scattered in the three-dimensional brain at the same time-just like we need to use ten fingers of both hands to play a coordinated piano music
.
Using two-photon holography technology, Dr.
Weijian Yang and his collaborators solved the above problems.
They were one of the first teams to stimulate a group of neurons distributed in three-dimensional space in the brain of living mice and record their activities at the same time
.
Using this technology, they showed how to use two-photon holographic optogenetics to efficiently control neural circuits and animal behavior
.
Figure: Two-photon holographic optogenetics can regulate neuronal groups distributed in the three-dimensional space of the brain
.
At the same time, two-photon three-dimensional calcium ion imaging can record the activity of neuronal groups
.
Through closed-loop regulation and recording of neural activity, researchers can establish a causal relationship between neural circuits and animal behavior, and then effectively regulate animal behavior
.
Two-photon holographic optogenetics technology Two-photon holographic optogenetics uses a spatial light modulator to encode the three-dimensional spatial information of the target neuron group into a hologram, so that the light beam projected into the mouse brain is focused on the corresponding neuron group In
.
The two-photon nonlinear excitation characteristic ensures that the transmitted light can penetrate deep into the brain tissue and only excite the focused neuron group
.
Researchers can stimulate more than 50 neurons at the same time; by quickly switching holograms, different groups of neurons can be stimulated in sequence
.
At the same time, through a two-path microscope, the researchers combined two-photon high-speed three-dimensional calcium ion imaging with two-photon holographic optogenetics to realize the "read" and "write" of brain activity at the same time
.
While accurately stimulating any group of neurons, researchers can monitor the response of neural circuits in real time, providing a technical basis for closed-loop regulation of brain activity
.
Regulating animal behavior Two-photon holographic optogenetics provides a very effective method for regulating brain activity and animal behavior
.
To confirm this, the researchers designed a visual recognition task
.
The mouse has to judge the direction of the moving grating on the screen to decide whether to lick a water outlet
.
The researchers found that in the visual recognition task, if a random set of neurons in the mouse visual cortex is stimulated, the task performance of the mouse will decrease
.
In contrast, if the core neuron group corresponding to the direction of the moving grating is stimulated, the task performance of the mice will be improved
.
Surprisingly, only a small number of core neurons in the neuron group (such as two) can be stimulated to stimulate the activities of other neurons in the neuron group, thereby regulating the behavior of the mouse
.
The "pattern completion" effect amplifies the stimulation of a small number of core neurons, greatly improving the efficiency of two-photon holographic optogenetics
.
Through the stimulating effect of this "pulling the whole body", researchers can also trigger the licking behavior of mice without a screen display, just as the mice actually see the corresponding moving grating
.
This study confirms that two-photon holographic optogenetics can accurately write information into the brain and trigger behaviors, providing a possible new solution for the treatment of brain diseases
.
Reshaping neural networks In addition to studying the causality of neural circuits, two-photon holographic optogenetics is also an ideal tool for inducing the plasticity of neural networks
.
By repeatedly stimulating a group of neurons, researchers can enhance the functional connections of this group of neurons
.
If a mouse is given a reward while stimulating a certain group of neurons, the mouse can learn to associate the excitation and reward of the neuron group, which has also been confirmed by multiple independent laboratories
.
These findings indicate that two-photon holographic optogenetics can program the brain and artificially create new links between neural circuits and animal cognition
.
Using this technology, people are expected to restore the functions of the damaged brain in other brain regions
.
Prospects: In the new era of precise regulation of brain nerve activity, looking forward to the future, two-photon holographic optogenetics has many potentials that can be unearthed
.
How to apply non-invasively or minimally to the deep brain regions will be an important research field
.
The closed-loop real-time control of imaging, optogenetics, and behavior monitoring is expected to create a new brain-computer interface
.
Two-photon holography technology brings optogenetics into the era of precision.
It will continue to play an important role in basic neuroscience and is expected to become a new tool for precision medicine
.
The Science-PINS neuromodulation award this time is the Associate Professor Stanisa Raspopovic from ETH Zurich.
His research focuses on in-depth understanding through computational modeling, the design of sensory neuroprostheses and bioelectronics solutions, and the study of the interaction between humans and electric fields.
The interaction of the nervous system with the electric field
.
Original link: https://science.
sciencemag.
org/content/373/6555/635 Plate maker: Notes for reprinting on the 11th [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting without permission is prohibited.
The author has all legal rights, and offenders must be investigated
.
.
Graduated from the Department of Electronics of Peking University in 2008; received a Ph.
D.
from the Department of Electronics at UC Berkeley in 2013; worked as a postdoctoral fellow in the Department of Biology at Columbia University from 2014 to 2017; joined at the end of 2017 Department of Electronic and Computer Engineering, University of California, Davis
.
He is currently engaged in the interdisciplinary research of electronic engineering and neuroscience, mainly developing advanced optical systems and neural technologies, and using them to monitor and control the activities of neural circuits, so as to gain insight into the organization and operation mechanism of neural circuits and nerves.
How the activity promotes animal behavior
.
Perception and behavior stem from the coordinated activities between neurons in the brain's neural circuits
.
Multiple interconnected neurons form a neuron group and become the unit that drives the complex functions of the brain
.
The precise regulation of neuronal group activity helps to analyze neural circuits and study the causal relationship between neural activity and animal behavior
.
It is also expected to play an important role in the treatment of brain diseases and become a new tool for precision medicine
.
Electrical stimulation is the most mature method of regulating brain activity
.
However, penetrating electrodes are highly invasive and lack cell-level resolution
.
All neurons near the electrode will be stimulated indiscriminately, which may cause off-target effects
.
This not only limits the application of electrical stimulation in the study of neural circuits and clinical treatment, but also may produce side effects in the latter
.
Optogenetics is a new method of regulating neural activity
.
Compared with electrical stimulation, optogenetics can act on specific cell types, but its early application in the living brain faces the same problem as electrical stimulation: incident light irradiates a large brain area, and many neurons will be destroyed.
Stimulate differently
.
Two-photon light solves the problem of spatial resolution
.
Borrowing laser scanning microscope technology, two-photon light can stimulate a single neuron in sequence
.
However, stimulating single cells sequentially cannot simulate the simultaneous activity of multiple neurons in the brain
.
To use an analogy, stimulating neurons is similar to playing the piano
.
Stimulating a single neuron at a time is like playing the piano with one finger, and it cannot produce rhythmic and melody music
.
In order to effectively regulate neural activity, we need to stimulate a group of neurons scattered in the three-dimensional brain at the same time-just like we need to use ten fingers of both hands to play a coordinated piano music
.
Using two-photon holography technology, Dr.
Weijian Yang and his collaborators solved the above problems.
They were one of the first teams to stimulate a group of neurons distributed in three-dimensional space in the brain of living mice and record their activities at the same time
.
Using this technology, they showed how to use two-photon holographic optogenetics to efficiently control neural circuits and animal behavior
.
Figure: Two-photon holographic optogenetics can regulate neuronal groups distributed in the three-dimensional space of the brain
.
At the same time, two-photon three-dimensional calcium ion imaging can record the activity of neuronal groups
.
Through closed-loop regulation and recording of neural activity, researchers can establish a causal relationship between neural circuits and animal behavior, and then effectively regulate animal behavior
.
Two-photon holographic optogenetics technology Two-photon holographic optogenetics uses a spatial light modulator to encode the three-dimensional spatial information of the target neuron group into a hologram, so that the light beam projected into the mouse brain is focused on the corresponding neuron group In
.
The two-photon nonlinear excitation characteristic ensures that the transmitted light can penetrate deep into the brain tissue and only excite the focused neuron group
.
Researchers can stimulate more than 50 neurons at the same time; by quickly switching holograms, different groups of neurons can be stimulated in sequence
.
At the same time, through a two-path microscope, the researchers combined two-photon high-speed three-dimensional calcium ion imaging with two-photon holographic optogenetics to realize the "read" and "write" of brain activity at the same time
.
While accurately stimulating any group of neurons, researchers can monitor the response of neural circuits in real time, providing a technical basis for closed-loop regulation of brain activity
.
Regulating animal behavior Two-photon holographic optogenetics provides a very effective method for regulating brain activity and animal behavior
.
To confirm this, the researchers designed a visual recognition task
.
The mouse has to judge the direction of the moving grating on the screen to decide whether to lick a water outlet
.
The researchers found that in the visual recognition task, if a random set of neurons in the mouse visual cortex is stimulated, the task performance of the mouse will decrease
.
In contrast, if the core neuron group corresponding to the direction of the moving grating is stimulated, the task performance of the mice will be improved
.
Surprisingly, only a small number of core neurons in the neuron group (such as two) can be stimulated to stimulate the activities of other neurons in the neuron group, thereby regulating the behavior of the mouse
.
The "pattern completion" effect amplifies the stimulation of a small number of core neurons, greatly improving the efficiency of two-photon holographic optogenetics
.
Through the stimulating effect of this "pulling the whole body", researchers can also trigger the licking behavior of mice without a screen display, just as the mice actually see the corresponding moving grating
.
This study confirms that two-photon holographic optogenetics can accurately write information into the brain and trigger behaviors, providing a possible new solution for the treatment of brain diseases
.
Reshaping neural networks In addition to studying the causality of neural circuits, two-photon holographic optogenetics is also an ideal tool for inducing the plasticity of neural networks
.
By repeatedly stimulating a group of neurons, researchers can enhance the functional connections of this group of neurons
.
If a mouse is given a reward while stimulating a certain group of neurons, the mouse can learn to associate the excitation and reward of the neuron group, which has also been confirmed by multiple independent laboratories
.
These findings indicate that two-photon holographic optogenetics can program the brain and artificially create new links between neural circuits and animal cognition
.
Using this technology, people are expected to restore the functions of the damaged brain in other brain regions
.
Prospects: In the new era of precise regulation of brain nerve activity, looking forward to the future, two-photon holographic optogenetics has many potentials that can be unearthed
.
How to apply non-invasively or minimally to the deep brain regions will be an important research field
.
The closed-loop real-time control of imaging, optogenetics, and behavior monitoring is expected to create a new brain-computer interface
.
Two-photon holography technology brings optogenetics into the era of precision.
It will continue to play an important role in basic neuroscience and is expected to become a new tool for precision medicine
.
The Science-PINS neuromodulation award this time is the Associate Professor Stanisa Raspopovic from ETH Zurich.
His research focuses on in-depth understanding through computational modeling, the design of sensory neuroprostheses and bioelectronics solutions, and the study of the interaction between humans and electric fields.
The interaction of the nervous system with the electric field
.
Original link: https://science.
sciencemag.
org/content/373/6555/635 Plate maker: Notes for reprinting on the 11th [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting without permission is prohibited.
The author has all legal rights, and offenders must be investigated
.
