Cell reviews the era of brain science 2.0

Written by | My Best Friend, Old Red Riding Hood In 2013, the National Institutes of Health launched the "Advancing Innovative Neurotechnologies (BRAIN) Initiative" (BRAIN) Initiative, which is dedicated to developing new research methods.
Strive to gain a deep and innovative understanding of the human brain
.

Many organizations and scientific research institutions from many countries and regions around the world participate in this program, and their research fields cover biology, physics, engineering and even clinical medicine (https://braininitiative.
nih.
gov)
.

In 2014, it has invested 2.
4 billion US dollars, and it is planned that the total investment will reach 5 billion US dollars by 2026
.

In 2019, experts from the NIH Review Committee summarized the pros and cons of the "Brain Project" in the past five years [1], and pointed out that the focus of the next stage of the "Brain Project" is to launch a high-throughput and large-dimensional research program with a view to The field of neuroscience has achieved revolutionary and even disruptive insights
.

On January 6, 2022, John Ngai, a member of the "Brain Project" from the National Institutes of Health, published a review article entitled BRAIN 2.
0: Transforming neuroscience in Cell, briefly describing 3 items in the next phase of the "Brain Project" Research plans include the establishment of a whole-cell atlas of the human brain, the construction of a mammalian brain cMap, and the development of a toolbox for precise targeting of various cells in the brain [2]
.

1.
Establishing a Whole-Cell Atlas of the Human Brain The study of human cognition and behavior requires a comprehensive and in-depth understanding of the proportions, characteristics, and signal transduction of various cell types in the brain.
Of course, the current understanding is far from enough
.

In 2014, the BRAIN Initiative Cell Census Consortium (BICCC) was launched, dedicated to the development of high-throughput and high-precision research tools, and based on this to accurately define and classify brain cells [3] ], and was merged into the "BRAIN Initiative Cell Census Network" (BICCN) in 2017 (one of the BICCN columns | General: the cerebral cortex motor neuron map landscape and the database alliance BICCN)
.

With the rapid development of single-cell sequencing technology, cell classification based on the integration of molecular, morphological, physiological, and anatomical information and characteristics of cells is the main work of BICCN
.

Hundreds of scientists from 3 continents participated in this work and accurately classified each cell type in the primary motor cortex of the mouse, marmoset and human brains [4]
.

In the next five years, the plan will enter the third phase, which is the "BRAIN Initiative Cell Atlas Network" (BICAN)
.

One of the important works is to construct a whole-cell map of the human brain from birth, development, maturity to aging, which will provide strong support for the study of the pathogenesis of neurodegenerative diseases, mental diseases, addiction,
etc.

At the same time, this plan also takes into account the influence of race and living habits on the map
.

Taken together, it is foreseeable that by the time this project is completed, one will have precise and complete knowledge of any cell in the brain
.

2.
Constructing the mammalian brain cMap Mapping the brain cell signal connection map (microconnectivity map, cMap for short) at the nanoscale will make a pioneering contribution to the field of neuroscience
.

This work not only helps to define distinct signaling modules under physiological and pathological conditions, to identify key neurons that perform their functions, but also to discover new cell types
.

However, the current technologies, both in data extraction and data processing, are insufficient to match the above-mentioned work
.

The mouse brain is about 500 cubic millimeters, and the human brain is a thousand times larger, but current electron microscopes can only measure 1 cubic millimeter
.

Scholars of the "Brain Project" and the Energy Office issued a memorandum (https://doi.
org/10.
2172/1812309), planning to focus on developing high-precision, large-scale imaging tools that can match the brain in the first five years; And draw cMap over the next five to ten years
.

Strive to complete the program in 2023
.

3.
Development of a toolbox for precise targeting of various types of cells in the brain With the development and innovation of optogenetics, chemical genetics and gene editing technology, we can edit the genome of brain cells to a certain extent, but this is only limited to worms , the germ cell level of model organisms such as Drosophila, zebrafish and mouse
.

With the gradual deepening of mammalian brain cells themselves and the signaling connections between cells, we need to develop a toolbox to precisely target certain types of cells in the brain
.

For example, specific modification of adenovirus can distinguish between neural cells and non-neural cells in the brain, and can pass the blood-brain barrier in mice [5]
.

Further modification of the enhancer may enable targeting of specific cell types [6]
.

Now is the ninth year of the implementation of the "Brain Project", and has achieved fruitful research results
.

With the in-depth progress of the three projects of establishing a whole-cell map of the human brain, constructing a mammalian brain cMap, and developing a toolbox that precisely targets various types of cells in the brain, the academic community is confident that it can lead the field of neuroscience into a new era
.

Original link: https://doi.
org/10.
1016/j.
cell.
2021.
11.
037 Publisher: Eleven References 1.
ACD BRAIN Initiative Working Group 2.
0.
(2019).
The BRAIN Initiative 2.
0: From Cells to Circuits, To-ward Cures (NIH BRAIN Initiative).
https://braininitiative.
nih.
gov/strategic-planning/acd-working-groups/brain-initiative%C2%AE-20-cells-circuits-toward-cures.
2.
Richardson, RR, Crawford, DC, Ngai, J.
, and Beckel-Mitchener, AC (2021).
Advancing scienti- fic excellence through inclusivity in the NIH BRAIN Initiative.
Neuron 109, 3361–3364.
3.
Ecker, JR, Geschwind, DH , Kriegstein, AR, Ngai, J.
, Osten, P.
, Polioudakis, D.
, Regev, A.
, Sestan, N.
, Wickersham, IR, and Zeng, H.
(2017).
The BRAIN Initiative Cell Census Con- sortium: Lessons Learned toward Generating a Comprehensive Brain Cell Atlas.
Neuron 96, 542–557.
4.
BRAIN Initiative Cell Census Network (BICCN) (2021).
A multimodal cell census and atlas of the mammalian primary motor cortex.
Nature 598, 86–102.
5.
Ravindra Kumar, S.
, Miles, TF, Chen, X.
, Brown, D.
, Dobreva, T.
, Huang, Q.
, Ding, X.
, Luo, Y.
, Ei-narsson, PH, Greenbaum, A.
, et al.
(2020).
Multi-plexed Cre-dependent selection yields systemic AAVs for targeting distinct brain cell types.
Nat.
Methods 17, 541–550.
6.
Mich, JK, Graybuck, LT, Hess, EE, Mahoney, JT, Kojima, Y.
, Ding, Y.
, Somasundaram, S.
, Miller, JA, Kalmbach, BE, Radaelli, C.
, et al .
(2021).
Functional enhancer elements drive sub-class-selective expression from mouse to primate neocortex.
Cell Rep.
34, 108754.
Instructions for reprinting【Original article】BioArt original article, you are welcome to forward and share it, and reprint is prohibited without permission.
The copyright of all works published is owned by BioArt, Huang, Q.
, Ding, X.
, Luo, Y.
, Ei-narsson, PH, Greenbaum, A.
, et al.
(2020).
Multi-plexed Cre-dependent selection yields systemic AAVs for targeting distinct brain cell types .
Nat.
Methods 17, 541–550.
6.
Mich, JK, Graybuck, LT, Hess, EE, Mahoney, JT, Kojima, Y.
, Ding, Y.
, Somasundaram, S.
, Miller, JA, Kalmbach, BE, Radaelli .
Reprinting is prohibited with permission, and the copyright of all works published is owned by BioArt, Huang, Q.
, Ding, X.
, Luo, Y.
, Ei-narsson, PH, Greenbaum, A.
, et al.
(2020).
Multi-plexed Cre-dependent selection yields systemic AAVs for targeting distinct brain cell types .
Nat.
Methods 17, 541–550.
6.
Mich, JK, Graybuck, LT, Hess, EE, Mahoney, JT, Kojima, Y.
, Ding, Y.
, Somasundaram, S.
, Miller, JA, Kalmbach, BE, Radaelli .
Reprinting is prohibited with permission, and the copyright of all works published is owned by BioArt, Kalmbach, BE, Radaelli, C.
, et al.
(2021).
Functional enhancer elements drive sub-class-selective expression from mouse to primate neocortex.
Cell Rep.
34, 108754.
Notes for reprinting【Original article】BioArt original article, Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
The copyright of all published works is owned by BioArt, Kalmbach, BE, Radaelli, C.
, et al.
(2021).
Functional enhancer elements drive sub-class-selective expression from mouse to primate neocortex.
Cell Rep.
34, 108754.
Notes for reprinting【Original article】BioArt original article, Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
The copyright of all published works is owned by BioArt
.

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