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Michael Totty @mictott.bsky.social · 2h

Learning induces persistent chromatin loops underlying robust gene expression during memory recall www.biorxiv.org/content/10.1...

Learning induces persistent chromatin loops underlying robust gene expression during memory recall

Long-term memories are stored in neuronal ensembles called engrams, but the existence of persistent molecular traces in nuclei of engram neurons remain unknown. Using activity-dependent nuclear taggin...

www.biorxiv.org

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Michael Totty @mictott.bsky.social · 1d

Locus Coeruleus-Amygdala Circuit Disrupts Prefrontal Control to Impair Fear Extinction. www.biorxiv.org/content/10.1...

Locus Coeruleus-Amygdala Circuit Disrupts Prefrontal Control to Impair Fear Extinction

Background Stress undermines extinction learning and hinders exposure-based clinical therapies for a variety of neuropsychiatric disorders. In both animals and humans, dysfunction in the ventromedial ...

www.biorxiv.org

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Reposted by Michael Totty

Pain Research Forum @painresforum.bsky.social · 6d

Have you wondered which neuron types are conserved across mammals and amygdalar subdivisions? Check out this article from @mictott.bsky.social et al. in Science Advances bit.ly/4pKcbkO #PRF #PapersoftheWeek

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Michael Totty @mictott.bsky.social · 6d

Congrats, Zach!

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Michael Totty @mictott.bsky.social · 20d

Single-cell long-read sequencing of the experience-induced transcriptome www.biorxiv.org/content/10.1...

Single-cell long-read sequencing of the experience-induced transcriptome

Neural activity drives transcriptional events that are critical for learning. Activity-induced transcript isoform expression and alternative splicing are cell-type specific events typically obscured b...

www.biorxiv.org

Michael Totty @mictott.bsky.social · 20d

Thanks, Stephanie!!

Reposted by Michael Totty

Stephanie Hicks @stephaniehicks.bsky.social · 20d

This was a really fantastic collaboration! Congratulations @mictott.bsky.social Rita Cervera Juanes,
@svitlanabach.bsky.social and all co-authors! 🧪🧬💻🧠

Michael Totty @mictott.bsky.social · 20d

Very excited to share my second postdoc, now out in Science Advances! We used targeted snRNA-seq to profile four major subnuclei of the primate across three species (including humans). 1/13 www.science.org/doi/10.1126/...

Transcriptomic diversity of amygdalar subdivisions across humans and nonhuman primates

Specialized cell types and links to psychiatric disorders are revealed by genetic mapping of primate amygdala neurons.

www.science.org

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Michael Totty @mictott.bsky.social · 20d

Yes, I am on the academic job market looking to start my own lab at the intersection of molecular, computational, and systems neuroscience! If you think my work may be interest to your department, please don't hesitate to reach out.

Thank you, Keri!

Keri Martinowich @martinowk.bsky.social · 20d

Congrats Michael! Really appreciate the brilliance & creativity you brought to the analyses and as always, sincere dedication to open science 🧪 🧠

@mictott.bsky.social is on the job market!! Amazing skillset spanning wet lab/computational at molecular, cellular + systems level - and across species!

Michael Totty @mictott.bsky.social · 20d

Very excited to share my second postdoc, now out in Science Advances! We used targeted snRNA-seq to profile four major subnuclei of the primate across three species (including humans). 1/13 www.science.org/doi/10.1126/...

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Reposted by Michael Totty

Keri Martinowich @martinowk.bsky.social · 20d

Congrats Michael! Really appreciate the brilliance & creativity you brought to the analyses and as always, sincere dedication to open science 🧪 🧠

@mictott.bsky.social is on the job market!! Amazing skillset spanning wet lab/computational at molecular, cellular + systems level - and across species!

Michael Totty @mictott.bsky.social · 20d

Very excited to share my second postdoc, now out in Science Advances! We used targeted snRNA-seq to profile four major subnuclei of the primate across three species (including humans). 1/13 www.science.org/doi/10.1126/...

Transcriptomic diversity of amygdalar subdivisions across humans and nonhuman primates

Specialized cell types and links to psychiatric disorders are revealed by genetic mapping of primate amygdala neurons.

www.science.org

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Michael Totty @mictott.bsky.social · 20d

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.

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Michael Totty @mictott.bsky.social · 20d

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

GitHub - LieberInstitute/BLA_crossSpecies: Collaboration between Costa, Martinowich, and Hicks labs investigating basolateral amygdala cell-types across huamn and non-human primate species.

Collaboration between Costa, Martinowich, and Hicks labs investigating basolateral amygdala cell-types across huamn and non-human primate species. - LieberInstitute/BLA_crossSpecies

tinyurl.com

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Michael Totty @mictott.bsky.social · 20d

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

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Michael Totty @mictott.bsky.social · 20d

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

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Michael Totty @mictott.bsky.social · 20d

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

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Michael Totty @mictott.bsky.social · 20d

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

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Michael Totty @mictott.bsky.social · 20d

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

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Michael Totty @mictott.bsky.social · 20d

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

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Michael Totty @mictott.bsky.social · 20d

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

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Michael Totty @mictott.bsky.social · 20d

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

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Michael Totty @mictott.bsky.social · 20d

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

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Michael Totty @mictott.bsky.social · 20d

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

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Michael Totty @mictott.bsky.social · 20d

Very excited to share my second postdoc, now out in Science Advances! We used targeted snRNA-seq to profile four major subnuclei of the primate across three species (including humans). 1/13 www.science.org/doi/10.1126/...

Transcriptomic diversity of amygdalar subdivisions across humans and nonhuman primates

Specialized cell types and links to psychiatric disorders are revealed by genetic mapping of primate amygdala neurons.

www.science.org

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Reposted by Michael Totty

Keri Martinowich @martinowk.bsky.social · 20d

Congratulations to @mictott.bsky.social, Rita Cervera Juanes and @svitlanabach.bsky.social and all co-authors! Really fun collaboration w/labs of @vincentcostaphd.bsky.social and @stephaniehicks.bsky.social to better understand cell type and spatial heterogeneity across amygdala in primate 🧠!

Vinny Costa @vincentcostaphd.bsky.social · 20d

A spatially resolved transcriptomic atlas of the primate amygdala (human, macaque, and baboon) now out in Science Advances (www.science.org/doi/10.1126/...). The amygdala contains 32 types of neurons with many neuron types specific to particular subdivisions.

Lots of updates from the preprint!

Transcriptomic diversity of amygdalar subdivisions across humans and nonhuman primates

Specialized cell types and links to psychiatric disorders are revealed by genetic mapping of primate amygdala neurons.

www.science.org

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Reposted by Michael Totty

Vinny Costa @vincentcostaphd.bsky.social · 20d

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.

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Reposted by Michael Totty

Vinny Costa @vincentcostaphd.bsky.social · 20d

Hot take #1: Amygdala neuron types are highly conserved across different primate species. No human specific innovations.

Hot take #2: Canonical gene markers identified for murine amygdala neuron types are not especially informative inferring cell type identifies for the primate amygdala.

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