Tony Zador Profile picture
Sep 16, 2020 11 tweets 4 min read Read on X
Does gene expression predict wiring in the cortex?

Here we introduce a new technique, BARseq2, to answer this question

BARseq2 looks at genes and axon projections at high throughput--thousands of single neurons and many genes per cell in parallel

doi.org/10.1101/2020.0…

1/n
This is work by an amazing team: Yu-Chi Sun, Xiaoyin Chen, Stephan Fischer, @starfishlu , and Jesse Gillis

(2/n)
BARseq2 builds on first-generation BARseq (cell.com/cell/pdf/S0092…), which let us look at barcoded axonal projections by in situ DNA sequencing

BARseq2 adds highly multiplexed sequencing of dozens of endogenous genes

shoulders of giants: @MatsNilssonLab @jlee8usa

(3/n)
We hypothesized that cadherin expression was key. So we used BARseq2 to detect cadherin expression and cell type markers in auditory and motor cortex

(4/n)
Laminar patterns of gene expression obtained by BARseq2 were similar to the that seen in the Allen Brain Atlas

(5/n)
The sensitivity of BARseq2 was similar to 10x v3 in this particular experiment, but if we push it we can reach at least 60% of RNAscope

(6/n)
We also determined transcriptomic cell types by detecting additional cell type markers in the motor cortex.

7/n
Combining in situ sequencing of barcodes and endogenous genes, we correlated cadherin expression to projections in 1,349 single neurons in auditory and motor cortex.

Gene expression+single neuron axon projection patterns in 1000 neurons, from just a handful of animals!

8/n
Our data recapitulated known differences in gene expression and projections between neuronal classes, types, and subtypes.

For example, neurons that project only ipsilaterally were mostly IT4 transcriptomic type (i.e. L6 Car3 type)

9/n
How do these cadherins relate to transcriptomic cell types?

To find out, we grouped cadherins into co-expression modules and found that these modules were associated with multiple branches of the transcriptomic taxonomy

10/n
Our results suggest that the relationship between gene expression and axonal projections in the cortex is complex

Probably not fully described by the transcriptomic types alone

Maybe the key is to look during development? Or at other genes? Stay tuned...

11/11

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More from @TonyZador

Nov 8, 2022
We used BARseq in situ sequencing to identify genes in ***1.2 million neurons*** throughout the mouse brain

We found that cortical areas with similar cell types are also interconnected. We call this “wire-by-similarity.”

biorxiv.org/content/10.110…
1/n
This work was led by Xiaoyin Chen (now at Allen), with lots of fun collaborations with Stephan Fischer, Aixin Zhang, Jesse Gillis.

They all apparently anticipated the current Twitter crisis long ago by not signing up, leaving me to deliver this tweetstorm

1.5/n
We originally developed BARseq as an extension of MAPseq to associate genes and projections using barcodes

Here we look only at endogenous genes in a mouse brain (no projection mapping)

It’s fast & cost-effective: 7 days of sequencing with $3k in reagents for this dataset.

2/n
Read 15 tweets
Dec 11, 2021
Biological neural networks (BNNs) are much more energy efficient than artificial NNs. The human brain uses about 15-20W, whereas eg training a big ANN causes the lights to dim in Boston for a day or 2.

Why?
1/n
The usual explanation for the energy efficiency of BNNs is sparse spiking.

Eg firing rate in the cortex is 1-0.1 Hz or less. Most neurons are silent most of the time.

Sparse spiking saves energy bcs repolarizing neurons requires energy expensive Na+/K+-ATPase pump

2/n
Read 6 tweets
Dec 10, 2021
I don't usually tweet politics, but I have an idea I would like to share

We (in the US) have a serious problem: Due to gerrymandering, many congressional elections are "safe":

Such districts are decided in the Republican primary rather than the general election.

1/n
Primaries are low turnout, and are dominated by the "party faithful", whose views are typically on the extreme of the party

So the winner of the R primary--and the general election-- in a safe district is often the most extreme candidate

And we are living with the result

2/n
However I think there is a simple solution: Dems in safe Rep districts should register as R, and vote for the less extreme candidate.

Dem voters can still vote D in the general election. And Rs will still win the district. But the winning R will be a bit less extreme.

3/n
Read 5 tweets
Nov 24, 2021
This is a really fun question.

I think there are clearly plenty of behaviors that are so far developed in humans as to be effectively unique.

I am particularly impressed by language, which enables social cooperation and the accumulation of knowledge through generations.
1/n
And we have some specializations related to dexterity (which enables tool use) and bipedality.

And our theory of mind is really sophisticated. We primates are really good at predicting others' actions; and when we started to predict our own actions, consciousness emerged
2/n
But I think @zmainen was asking more than this.

I think every (or maybe just many/most) species have specializations. Eg bats are specialized for ultrasound localization; elephants surely have brain specializations for their trunks; etc.

3/n
Read 6 tweets
Sep 26, 2020
We touched on a lot of interesting subjects at the great Salon yesterday

But i would like to dig into one where i think we failed to communicate: what it means to be "close" in genetic space, and why i think it's relevant. (1/n)

@criticalneuro @neuro_data @MelMitchell1
Suppose i am trying to solve eg a prediction task, where I take inputs from a set X and try to predict Y. Maybe X is a set of images, and Y is a set of labels.

Now let's say that i try to solve it with my favorite algorithm, and fail. (2/n)
I take it to one of you, and you say, "Oh, i see the problem, you just need to pre-process your images with this edge detector" or "You just need to use weight momentum to make your network converge". (3/n)
Read 15 tweets
May 26, 2020
Should we rethink the standard science seminar, especially delivered by zoom?

I find zoom seminars much less engaging than a live delivery, both for departmental seminars and especially conferences.

Maybe there are alternatives?

1/n
If we're gonna stick with the standard seminar format, maybe make it offline, edit it for clarity, and post to youtube for asynchronous viewing?

The advantage of zoom live seems minimal...maybe just a few questions at the end.

Missing the sense of shared experience

2/n
Better yet, take inspiration from all the amazing popular science videos

(I watch a lot with my 10 yo, and i'm impressed!)

This might be a lot of work, but maybe less than the 14 gazillion hours I spend writing a paper

(Admittedly not for everyone, probably including me)

3/n
Read 6 tweets

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