10.5 Mapping synaptic connections

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Do curso por Peking University

Advanced Neurobiology I

248 classificações

Peking University

Advanced Neurobiology I

248 classificações

Hello everyone! Welcome to advanced neurobiology! Neuroscience is a wonderful branch of science on how our brain perceives the external world, how our brain thinks, how our brain responds to the outside of the world, and how during disease or aging the neuronal connections deteriorate. We’re trying to understand the molecular, cellular nature and the circuitry arrangement of how nervous system works. Through this course, you'll have a comprehensive understanding of basic neuroanatomy, electral signal transduction, movement and several diseases in the nervous system. This advanced neurobiology course is composed of 2 parts (Advanced neurobiology I and Advanced neurobiology II, and the latter will be online in late April or May). They are related to each other on the content but separate on scoring and certification, so you can choose either or both. It’s recommended that you take them sequentially and it’s great if you’ve already acquired a basic understanding of biology. Thank you for joining us!

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Techniques in neuroscience

Let's learn some prevalent techniques in neuroscience.

10.1 Observation and perturbation10:53

10.2 Animal models in neurological research17:02

10.3 Genetic and molecular techniques12:33

10.4 Anatomical techniques15:37

10.5 Mapping synaptic connections6:48

10.6 Patch recording and optical imaging3:27

Conheça os instrutores

Yan Zhang
Professor
School of Life Sciences, Peking University
Yulong Li
Research Fellow
School of Life Sciences, Peking University

And in natural mycospic because of its superior spatial resolution,

one can look at a vesicle and density the PSD and

one can [COUGH] trace this

synapse if one has a different section of a different brain.

So this illustrates segmentation that people can

label based on electrical micrograph which cell is which cell.

And then, if you imagine, that if you have lost tracing,

you can trace which cell is which cell.

Then, if you cut different depths of this.

And in reconstruction you can achieve with high

spatial resolution the kinetomics of a mouse brain or

part of the human brain, okay?

Again, there are increasing efforts for different groups are trying to do that.

Right now the difficulty is how to cut perfect slice.

And how to perfectly align them.

How to computationally, efficiently trace them without the human intervention.

Because traditionally people can only, by eye and each person can trace and

that takes a lot of efforts, including some of my students in the lab.

So how do you allow it using artificial intelligence?

Some smart computer algorithm to automatically trace them and

then reconstruct them.

Those will pose challenges for

computer scientists, for students whose major or

second major is in math to develop techniques for those reconstructions.

Again, this is a one requires real interdisciplinary approaches.

Because, I guess 90% of the computer scientists doesn't care or

didn't know there is this huge challenges in brain reconstruction, okay?

And 80% of the brain scientists doesn't know how to use the computer science or

advanced algorithm techniques to trace those brain regions.

And even for 20% of them I know those techniques, 90% of them

doesn't know how to compute the electron micrograph to cloud the status.

They don't know how to use a diamond knife to cut the brain slice.

Okay, so it really requires the interdiscipline approaches.

And we can go on, and on, and on.

And this illustrates that one reason develop techniques again

using the virus to trace the neuron connections.

We just mentioned that the virus has this problem.

If we infect the cells, it will just reproduce and

then spread, label the whole bread.

So how do use a virus to label specific cell, or

a cell assembly that are connected?

Well, Edward Holloway and his collaborators designed a mass strategy.

Furthermore, how do you label a specific cell?

Well, they engineered a virus because virus requires using

a envelope protein to target a cell to its [INAUDIBLE].

Okay, so they engineer the virus,

only put in a virus with a special envelope protein.

And this envelope protein will only recognize this specific TVA receptor.

For example, this TVA receptor is from a chicken virus.

Okay, and if you only it's present in mouse.

There's no chicken receptor there, okay?

So only is present this receptor in a cell of interest to, you are interested in.

Then you are putting this virus, then this virus can only infect this cell, okay?

How do you only express this TVA in this cell?

Well, we just talked about you can use this tissue specific promoter, okay?

Express this TVA in itself, okay?

And then, this virus can only express in this cell.

And then, this cell was different color, for example, it was GIP, okay?

But then what you can do is that this virus

can only reproduce in your cell, okay?

Because you put in this virus lacking a special gene.

So it cannot self

reproduce unless it is present in this cell.

Where in this cell you also express a special gene that

this virus is lacking, okay?

So, only when this virus is pressed in this cell.

And then the cell also provide a glycoprotein to compliment this virus and

then this virus can reproduce, get release, okay?

And once it release, then it can retrogradely label other

cells that has this synaptic connection with it, okay?

And once it label this cell because of the other

cell do not have this glycoprotein.

Then those virus in that other cell will not reproduce, okay?

So, you only label this cell, okay?

So essentially, you allowed this virus to spread only one step, okay?

And you're only looking at one cell and

its connecting cell and no other cell, okay.

And using this method,

people have generating some specific connection map for certain cells.

And then you can imagine this vessel can be reused again.

For example, if you're using and another color and

yet another complementation in these cells.

And then you can from this cell to label another cell with a different color.

Okay, so you can use over and

over again to trace the one synapse connection and two synapse connection.

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