Adv. SCI: Cell type-specific single-neuron level whole-brain function projection mapping method

Innovation: The team broke through the limitation that genetic calcium probes can only be used for neuronal activity recording, and used the fMOST system to collect GCaMP6-labeled single neuronal whole brain fine structure
.
Through cross-modal cell registration, the functional response and axon projection information of the same neuron were obtained, and a research method
of single neuronal whole brain functional projection with cell type specificity was established.
This method provides a new way
to parse the organizational rules of neural information flow.

Keywords: functional projection mode of single neurons, HD-fMOST, two-photon in vivo calcium imaging, GCaMP6, brain-spatial informatics research team of Huazhong University of Science and Technology

Fig.
1 Acquisition
of whole-brain projection function annotations (FAWPS) at the single-neuron level.

Fig.
2 Functional characteristics
of single neuron projection targets.

The brain is a complex system
of hundreds of hundreds of millions of neurons.
Neurons are interconnected through rich axonal projections to form an information processing network
.
The axon projection pattern of the whole brain is one of the important indicators for understanding the type of neurons, and the whole brain projection map at the level of a single neuron has become an important part of the mesoscopic map of
the whole brain.
However, there is a lack of methods to integrate the functional response of single neurons with complex projection patterns
.

In response to this problem, the brain-spatial informatics research team of Huazhong University of Science and Technology used the sparse labeling of the genetic function probe GCaMP6 to combine two-photon calcium imaging in vivo and fMOST imaging in vitro.
Through cross-modal precise matching, the information of in vivo calcium imaging and high-resolution whole brain imaging is integrated on the same neuron object, and finally the functional annotation of whole-brain projection at the single neuron level (FAWPS) is obtained (Figure 1).

The acquisition of FAWPS provides a basis
for studying the relationship between intact whole-brain projection and function of neurons.
The team applied this method to the 2/3 layer neurons of the mouse visual cortex, preliminarily explored the association between neuronal visual preference characteristics and whole brain projection, and found the motif pattern of the projection target related to function (Figure 2) and the projection intensity pattern
of specific targets.
The results were published in
Advanced Science.

Realizing the reconstruction of single-neuron whole brain axons through the labeling of functional probes is a new attempt
.
This method specifically solves the problems
of sparse labeling of probes, fluorescence signal enhancement and signal-to-noise ratio improvement.
Fine structural imaging results confirm that the axonal labeling of GCaMP6 is similar to that of membrane localization proteins, and the brain-wide axon-signal-to-back ratio obtained by HD-fMOST is comparable to the widely used GFP signal, ensuring the reliability
of single-neuron axonal complete reconstruction.
In this way, the functional probe GCaMP6 has become a bridge connecting the function of the same neuron with the whole brain structure imaging, providing an easy scheme
for studying the relationship between neuronal whole brain projection and function.

This method is a highly scalable scheme with a wide
range of potential applications.
Genetic functional probes can be combined with molecular type-specific labeling methods to obtain neuronal information of multiple dimensions of cell type, function and whole brain projection.
At the same time, this method also has the potential to combine with other genetic functional probes to explore the relationship between
more functional information and projection.

WILEY

Paper Information:

Mapping the Function of Whole-Brain Projection at the Single Neuron Level

Wei Zhou*, Shanshan Ke, Wenwei Li, Jing Yuan, Xiangning Li, Rui Jin, Xueyan Jia, Tao Jiang, Zimin Dai, Guannan He, Zhiwei Fang, Liang Shi, Qi Zhang, Hui Gong, Qingming Luo, Wenzhi Sun*, Anan Li*, Pengcheng Li*

Advanced Science

DOI:10.
1002/advs.
202202553

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.

Advanced

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