Mystic Q&A with Scientist Ashwin Vishwanathan

#1

Hello!

Seung Lab’s Ashwin Vishwanathan will host a Q&A in Eyewire chat on Monday, August 21 at 4:30 pm US ET. If you can’t join us, leave your questions below and we’ll pass them to Ashwin and share his responses after Q&A concludes.

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#2

I’ll probably be able to attend :smiley: but here’s a question which is not exactly on the paper but it is on the zfish (cells) lol

What does the naming of the cells mean?

SN-#####-###
old#_#
DC####-##
Abd-##
IO-#######-####

Are they based on different cell types, method of finding them, position in the dataset (layers etc) or something else?

thank you. :slight_smile:

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#3
  1. Can you describe in a few words for a layman, what the new paper is about?
  2. Why larval zebrafish, not fully grown specimen (and why zfish at all??
  3. Was there any screening done before selecting this particular fish? Can we be sure, that it doesn’t have any mutations or sth and is a typical representative of the species?
  4. How big is hindbrain in relation to a full brain of a zfish?
  5. Is there an equivalent of hindbrain in human brain?
  6. How is hindbrain connected with retina? Is it a direct connection (axons from hindbrain to retina or dentrites from retina to hindbrain) or is there any sctructure in the middle?
  7. Where the signal from hindbrain goes after being processed in it?
  8. Are neurons (cell bodies), on average, bigger or smaller than those in the mouse retina?
  9. We are only humans and we sometimes make errors. How much influence on the research can have a couple of missing or incorrectly added branches here and there?
  10. What kind of neurons have been found so far in the dataset?
  11. What are those contra and ipsi synapses?
  12. What a zebrafish can see? Do they see colors, some infrared or ultraviolet spectrum? Do they see better or worse than human on distance or in darkness?

Sorry, if some (or all) the questions were already answered in the paper - I haven’t read the whole yet, and thanks for all the hard work! :slight_smile:

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#4

were the 25 (?) integrator neurons traced by princeton admins/tracers or were they pre-traced when Seung Labs received the zfish sample from Cornell (?) . Are there Cell Id/cube ID we can jump and see them? Or 3D models we can see during/after the Q+A? (I’m assuming they are known and traced based on Ashwin picking cells synapsing with them?)

#5

How does the brain of a zebra fish compare to the brain of an insect like an ant? I know a lot of researchers are studying fruit flies, especially at Princeton, but what about other insects?

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#6

Once you finish mapping, what’s next? Do you plan lesion studies or tracking development of specific cell classes? Or. . .?

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#7

Hey,

Thanks for the question. The names of the cells correspond to either where they are located or which specific nuclei in the brain they belong to. For example;

  1. SN-1695366-76181-1 would correspond to cube 1695366, has a seed piece at a synapse from cell 76181 and it is the first one that was encountered.
  2. Old## are the cells that were part of the 22 cells that were published.
  3. DC - stands for Dorso-Caudal, where the seed pieces were located.
  4. Abd - are cells that belong the Abducens nuclei in the brian.
  5. IO - are cells that belong to the Inferior Olive.
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#8

Hey,
These are all very good questions, I’ll try my best to answer them.

  1. Can you describe in a few words for a layman, what the new paper is about?

The paper was looking to validate previously proposed computational models of how these cells in the brain are connected. Until now, we had assumed that the cells that are responsible for eye-movement behavior should be ‘connected’ in a certain manner, based in what the electrical recordings from these areas suggested. But only through EM can this connectivity be studied.

  1. Why larval zebrafish, not fully grown specimen (and why zfish at all??

A few reasons, the behavior that we are studying is the eye-movement behavior, and they are present at this larval stage. Second, at this larval stage, the animal does not have any pigmentation, completely transparent. This makes it easy to look at activity using a light microscope. Third, since EM is very time consuming, a small brain is more easily reconstructed as compared to a large brain

  1. Was there any screening done before selecting this particular fish? Can we be sure, that it doesn’t have any mutations or sth and is a typical representative of the species?

Technically, these fish are mutant fish. This particular fish was developed to reduce any residual pigmentation, making it more optically accessible. I am not sure what sth is?
4.How big is hindbrain in relation to a full brain of a zfish?
The hind brain is roughly 1/3rd in physical dimensions of the actual brian.

  1. Is there an equivalent of hindbrain in human brain?

Yes, it is the brian stem. Everything that sits below the cerebellum and what comes before the spinal chord.

  1. How is hindbrain connected with retina? Is it a direct connection (axons from hindbrain to retina or dendrites from retina to hindbrain) or is there any structure in the middle?

As far as we know, there are no direct connections from the retina to the HB. There are intermediate structures like the optic tectum were the axons of retinal cells converge onto dendrites of tectal cells. The axons of these cells then shuttle the information to other brain regions like the cerebellum.

  1. Where the signal from hindbrain goes after being processed in it?

These particular cells that we are interested in send their information to a group of cells in the abducens nuclei that then send their axons to the eye-muscles. But in general many major nerves originate from the hindbrian.

  1. Are neurons (cell bodies), on average, bigger or smaller than those in the mouse retina?

Yes, the cell bodies are typically around 3-5 microns in diameter. As compared to 10-15 microns in the retina.

  1. We are only humans and we sometimes make errors. How much influence on the research can have a couple of missing or incorrectly added branches here and there?

this is one reason to have redundant tracing efforts. Have the same neurons reconstructed by a few individuals. This is also why statistics report the results with error bars and confidence intervals.

  1. What kind of neurons have been found so far in the dataset?

Yet to be determined. But that is one of the goals.

  1. What are those contra and ipsi synapses?

Ipsilateral refers to the same side ad Contralateral refers to the opposite side. Our dataset is only one half of the hindbrain. So we refer to axons, and synapses as originating/terminating either on the same side ( as the imaged volume) or the opposite side.

  1. What a zebrafish can see? Do they see colors, some infrared or ultraviolet spectrum? Do they see better or worse than human on distance or in darkness?

As far as I can tell, they can see color, I am not sure about the entire spectral range. I dont know much about their vision in darkness. But they need regular light/dark cycles for normal development of their eyes.

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#9

Hey,

the 22 integrator neurons were traced by largely by myself. Early on we had another tracer at Cornell helping. The cells labeled Old## are the cells in question. They were identified as their activity was highly correlated with eye movement.

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#10

Hey,

I am not sure how it compares to an ant, but I am sure there may be regions of the brain that are conserved. Most model systems that are studies have a long history and extensive literature to refer to, not to mention the collective knowledge of many labs. This is what goes into selecting the right model system that you want to study.

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#11

Hey,

Once we finish mapping, we would first like to analyze what the reconstructions mean. This will inform us on future studies where we would like to lesion etc, but will tell us where to lesion and what specific sets of cells to lesion.

#12

Thank you for your answers. Very clear and understandable. Now I’m even more eager to read the paper fully and thoroughly.
When talking about screening, I was worried, that the studied fish maybe was partially blind or had some kind of a fish daltonism, which would distort the studies “a little bit”, hence the question.

P.S.
“sth” means just “something” :slight_smile:

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#13

Thank you a lot for the answers! :slight_smile:

#14

Thank you for the answers!

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