1 Cell and 1 Cell sub-journal reveal that growing neurons gain competitive advantage by forming synapses

News March 20, 2021/bioon.
com" target="_blank">/---In a new study, researchers from Stanford University in the United States found that a bit of competition is never a bad thing, especially in the newborn neurons that grow in the brain.
They used bioon.
com/course_video/zhong-guo-ren-qun-ying-yang-he-yi-chuan-yin416058.
html">genetic experiments and computer models to elucidate two important steps in the development of the young mouse brain: branch extensions called dendrites grow on the cell bodies of neurons, and the connections between dendrites and other neurons.
Just like biological antennas, dendrites receive incoming signals from other neurons through connections called synapses.
They found that the dendrites of growing neurons compete with each other to form connections with their partners, and the presence of successful connections increases the chance of dendrites growth.
Related research results were recently published in the Cell journal, and the title of the paper is "Differential encoding in prefrontal cortex projection neuron classes across cognitive tasks".
The corresponding authors of the paper are Liqun Luo, Stephen R.
Quake and Jan H.
Lui from Stanford University.

bioon.
com" target="_blank">bioon.
com/course_video/zhong-guo-ren-qun-ying-yang-he-yi-chuan-yin416058.
html">Genetic

The picture is from Cell, 2021, doi:10.

1016/j.

Brain connection

Brain connection

Luo explained that this is because how neurons grow is a chicken-and-egg problem.
Do dendrites have to exist before synapses can be formed? Or is the formation of synaptic connections crucial to the growth of dendrites?

According to a view called the synapse hypothesis, synapses stabilize dendrites, making them more likely to grow further, while dendrites without synapses are more likely to weaken.
Luo said that as far as he knows, this idea has never been tested in the developing mammalian brain before.
Therefore, he decided that his laboratory would be the first to do so.

The Luo laboratory specifically explores how neural circuits are formed during development and how they are assembled to perform specific functions.
For more than two decades, his laboratory has often used Purkinje cells to study these problems, among which Purkinje cells are the main neurons in the cerebellum that affect motor and cognitive functions.

Luo said, "Purkinje cells are my first love.
This is because when I was a postdoctoral fellow, they were the first mammalian neuron I studied.
They look like beautiful trees, and there are many bioon.
com/course_video/zhong-guo-ren-qun-ying-yang-he-yi-chuan-yin416058.
html">genetic tools.
Study them.
"

bioon.
com/course_video/zhong-guo-ren-qun-ying-yang-he-yi-chuan-yin416058.
html">Genetic

Among these bioon.
com/course_video/zhong-guo-ren-qun-ying-yang-he-yi-chuan-yin416058.
html">genetic tools, several were developed in Luo's laboratory, such as "Mosaic Analysis with Double Marker (MADM)" technology, which removes a gene of interest from isolated cells , And mark these cells with a unique marker.

bioon.
com/course_video/zhong-guo-ren-qun-ying-yang-he-yi-chuan-yin416058.
html">Genetic

Luo explained, imagine that a Purkinje cell is a tree.
"Marking individual cells allows you to light up an entire tree in a dense neuron forest.
However, if all Purkinje cells are marked, it is difficult to imagine a single tree.
"

Growing Purkinje cells form circuits through synapses.
These synapses are organized into layers, with cerebellin-1 (Cbln1) molecules on one side and glutamate receptor delta 2 protein (glutamate receptor delta) on the other side.
2, GluD2).

In this new study, Luo's team used several different methods to alter the Cbln1 and GluD2 genes.
They also use computer models that simulate dendritic growth and synapse formation to further explore their research questions.

In an experiment, these researchers used MADM and other techniques to manipulate Purkinje cells in developing mouse embryos, knocking out the GluD2 gene, and marking these knock-out cells.

These researchers found that knocking out the GluD2 gene in all Purkinje cells had no significant effect on dendritic growth, but when only the isolated Purkinje cells lost the GluD2 gene, the results were amazing.

Purkinje cells with functional GluD2 gene grow in their usual box-like shape, with evenly distributed dendritic branches at the bottom (early growth) and top (late growth) of the tree.
In contrast, Purkinje cells lacking the GluD2 gene have almost no dendritic growth in the early stages, resulting in the shape of Purkinje cells resembling an inverted pyramid.

Luo said, “The key to this study is to be able to compare adjacent Purkinje cells with the GluD2 gene and Purkinje cells lacking the GluD2 gene.
This reveals how dendrites compete for synapses and how they Grow with normal or reduced synapses to stabilize them.
"

These researchers were surprised by the inverted pyramid shape of Purkinje cells lacking the GluD2 gene.
Luo said, "The lack of early dendritic growth is predicted by the synapse hypothesis, but the overgrowth of dendrites at the top in the later stages of development is not expected.
" He added that one possible explanation is the possibility of synapse formation.
It helps in the early stage, but inhibits the growth of dendrites in the later stage.

The findings of this study have led the Luo laboratory and the neuroscience community to take a step towards understanding how the brain is connected during development.
Luo said, "This is basic science, but it also has an impact on neurodevelopment and mental illness.
" (Bioon.
com)

References: 1.
Jan H.

Lui et al.
org/10.

References: 1.
Jan H.
Lui et al.
org/10.
1016/j.
cell.
2020.
11.
046" target="_blank">Differential encoding in prefrontal cortex projection neuron classes across cognitive tasks .
Cell, 2021, doi:10.
1016/j.
cell.
2020.
11.
046.
2.
Yukari H.
Takeo et al.
org/10.
1016/j.
neuron.
2020.
11.
028" target="_blank">GluD2 -and Cbln1-mediated competitive interactions shape the dendritic arbors of cerebellar Purkinje cells .
Neuron, 2021, doi:10.
1016/j.
neuron.
2020.
11.
028.
3.
Stanford study reveals growing neurons gain an edge by making connections
https://news .
stanford.
edu/press-releases/2021/03/11/growing-neurons-king-connections/ org/10.
1016/j.
cell.
2020.
11.
046" target="_blank">Differential encoding in prefrontal cortex projection neuron classes across cognitive tasks org/10.
1016/j.
neuron.
2020.
11.
028" target="_blank">GluD2- and Cbln1-mediated competitive interactions shape the dendritic arbors of cerebellar Purkinje cells