Congrats, Zach!

Thanks, Stephanie!!

A huge thank you and congrats to all of my co-first authors, Rita Cervera Juanes and @svitlanabach.bsky.social, and my mentors and collaborators @martinowk.bsky.social @vincentcostaphd.bsky.social, @stephaniehicks.bsky.social.

We hope that this data will be a valuable resource for the broader community. We have developed in-browser shiny apps to explore the processed data available on the github page (tinyurl.com/2jnascj9), and all raw data is currently available via GEO (GSE281366). 12/13

Finally, leveraging the human dataset, we conducted cell type enrichment for heritability of psychiatric traits (GWAS), as well as MDD and PTSD-associated transcriptomic changes. Aligning with previous literature, we found that GABAergic neurons were enriched for both. 11/13

Of importance, using the Yu et al dataset, we found amydala neuron types were markedly less conserved from humans to mice than humans to NHPs. While one to one cell type mapping could still be observed for inhibitory neurons, this was not true for excitatory cells. 10/13

Leveraging the precise subregion punches in NHPs, pseudobulk differential analysis revealed highly specific marker genes for excitatory neurons found in the LA, BA, and aBA across species. We confirmed these novel markers using in situ hybridization in both humans and macaques. 9/13

Moving onto excitatory neurons, we found that the LA, BA, and aBA subnuclei are almost exclusively composed of distinct classes of excitatory neuron types, and these neurons display relatively strong cross-species conservation (though less than inhibitory). 8/13

Within the BLA, we additionally found the aBA contains a large number of CCK+/CNR1+ interneurons, and that the LA, BA, and aBA nuclei were enriched for distinct subpopulations of SST+ and PVALB+ neurons. 7/13

Compositional analyses using linear mixed models (crumblr) found that the central nucleus was enriched in neurons derived from the LGE (PRKCD+, SST/TAC1+, DLK1+, etc), whereas the BLA is enriched in MGE (SST+,PVALB+) and CGE (LAMP5+, CCK+) cell types. 6/13

For inhibitory neurons, we found a wide variety of cell types (putatively) spanning medial, caudal, and lateral ganglionic origins - including two intercalated cell types (TSHZ1+) - which all displayed strong cross-species conservation. 5/13

This resulted in ~130,000 single nuclei across the three species, capturing a wide diversity of inhibitory and excitatory neurons, as well as non-neuronal populations. 4/13

Despite the difficulties working with fresh frozen postmortem brains, @svitlanabach.bsky.social
was able to precisely capture the basolateral complex from 5 human donors. We then performed cross-species integration to decode subnuclei origins of human amygdala cell types. 3/13

In a multi-institute effort, we conducted snRNA-seq of the baboon, macaque, and human amygdala. In baboons and macaques, @vincentcostaphd.bsky.social and his lab were able to take precise punches of the lateral (LA), basal (BA), accessory basal (aBA), and central nuclei (CeA). 2/13

Hot take #3: “BLA subdivisions contain specific subtypes of excitatory and inhibitory neurons.

Hot take #4: Genes downregulated in PTSD load mainly onto specific subtypes of inhibitory interneurons that are highly conserved across primates.