Great news! Sara’s work on characterizing the neurons involved in odor interpretation has been published in Nature Neuroscience (see here, or check the BiorXiv version). It took a serious amount of effort over several years, which makes me very proud of Sara’s accomplishments and of the contributions by all the co-authors. This study was really a team effort. For those of you who are now thinking “TL;DR” and for those who do not have access to the NN version (though this link may help), let me list the key findings:
- We performed combined scRNA and scATAC sequencing on mouse olfactory cortex (aka piriform cortex, or Pir), a transition area, and a neocortical area (somatosensory cortex, related to touch, body position, etc.).
- We find gradients of expression both along cortical depth and from anterior to posterior Pir. And these are much more prominent than similar gradients in neocortex.
- Between Pir and neocortex, pyramidal neurons open different parts of their genome for transcriptional regulation and other genome-related processes. Despite this strong difference, we find many of these neurons have rather similar transcriptomic profiles.
- And when comparing Pir and neocortex, we observe more transcription factor (TF) co-expression and through GRN inference we predict less TF-TF repression.
- Posterior Pir has a relatively large number of adult immature neurons. We predict that they become pyramidal neurons and suggest they contribute to differences between lab and wild-derived mice; perhaps implied in circuit plasticity.
- When comparing mouse Pir (pyramidal) neurons to mouse neocortex and cortical areas of three other vertebrate species —that is turtle, lizard, and salamander— we find that Pir neurons are closer to the other vertebrates than mouse neocortex.
In summary, our description of olfactory cortex neurons suggests that (a subset of) olfactory and neocortical neurons use rather distinct regulatory mechanisms to accomplish the same molecular tasks, with the olfactory mode being the “evolutionary old” one. From a network theoretical perspective, the pervasive rewiring of regulatory networks between the cortical areas was surprising. It appears that these neuronal cell types are not made by rewiring one or two regulatory interactions, but by implementing two completely different regulatory networks side by side. Nevertheless, they are recognizable as neurons with a similar molecular portrait.
Disclaimer: for the sake of brevity and accessibility, I have simplified terminology. I refer to the article itself for the more precise formulation of our findings.