There's been an explosion of papers doing cell-type specific research in rodent neuroscience lately. Any human neuroscience researchers here who could tell us whether and how much all these studies are relevant for human brain circuits?
@manisha from a comparative anatomy perspective, I think it is very important. It provides insight into mammalian brain evolution and phylogenetic differences. Would ideally like to see more across-species comparisons (which is difficult to do). #neuroscience
@alicia_izquierdo
@manisha
Last I was into this literature at all like 5 years ago there wasnt a rly principled way of making comparisons, the wisdom was "what is a cell type anyway?" I guess a safe hunch would be that has probably changed, and am curious both about manisha's question and the current thinking about how cell types are identified/compared.
@jonny @alicia_izquierdo @manisha
In the retina, people have started to match cell types across species using transcriptomics. Also, cell types are typically well defined because of the tiling principle (dendritic fields of same-type cells typically "repel" each other).
Recent awesome work here: https://www.nature.com/articles/s41586-023-06638-9
@manisha @alicia_izquierdo @dimokaramanlis
@jonny
Loving the discussion in this thread. For dendritic tiling, one candidate would be clustered protocadherins, a group of 60 cell-surface genes in 3 clusters, some with weird split-promoters.
Their expression is randomized, and thought to form a combinatorial code that allows self-avoidance and (potentially) other-recognition.
In Retina:
https://www.jneurosci.org/content/38/11/2713.full
Structural interaction:
https://elifesciences.org/articles/72416
Review:
https://link.springer.com/article/10.1007/s12264-020-00578-4
@moritz_negwer fascinating! TIL about protocadherins - potential neuronal identity tags, thanks!! @alicia_izquierdo @dimokaramanlis @jonny
@manisha
@moritz_negwer @alicia_izquierdo @dimokaramanlis
Someone tell the cryptography ppl that cells identify themselves with some collision avoidant hash based on genetic proximity
@alicia_izquierdo I was trapped in the "what's the translational benefit of such research?" and you raise an excellent point about such studies being important for studying evolution and phylogeny! thank you
@dimokaramanlis that is a great example! I hadn't seen this work before. Thanks for sharing!
I'll be honest, I had completely forgotten about the tiling principle they taught us in grad school 🙈. Though, I'm not sure if this is observed throughout the brain or only in the visual/sensory areas? Reading this now: https://www.sciencedirect.com/science/article/pii/S0092867404009493 and love the last line:
Finally and perhaps the most enigmatic of all, what allows dendrites of different neuronal types to distinguish self from nonself?
This adds another layer to answer @jonny's question "what is a cell type anyway" -- the "who am I" when it comes to a cell. Maybe it would it be fair to say that when neuroscientists talk about cell-types, they are mostly referring to the cells' genetics but sometimes also to the inputs that they receive? the classic nature vs nurture "debate", but at a cellular resolution :)
as an aside, I saw this in the author contributions:
M.M. performed the GAGE analysis
I am not a vision researcher, so of all the authors I only recognized Markus Meister's name from the time when I was reading up on efficient coding and decorrelation. It's so refreshing to see even senior scientists like him continue to actively do the analysis work! I was under the impression that senior PIs completely stop doing experiments and analyses themselves.
#neuroscience