Michael Totty

Michael Totty

@mictott.bsky.social

Research Scientist at the Lieber Institute for Brain Development. https://mictott.github.io

390 followers740 following134 posts

Cool paper, but I'm confused how they are dividing CeA cell types into appetitive and aversive. Saying that CeA-SST neurons "can contribute to fear learning" but are predominately appetitive is certainly a stretch.

Michael Totty reposted

Very excited to share our newest preprint, led by myself and Biostats PhD Student Jianing Yao, where we generate a three dimensional reconstruction of the human NAc to understand how cell type heterogeneity and topography change across the anterior-posterior axis. www.biorxiv.org/content/10.6...

Michael Totty reposted

🧪🧪🧪 (1/5) Beyond thrilled to announce that I’ll be starting my own lab as a Tenure-Track Assistant Professor at the University of Tennessee Health Science Center (@uthsc.bsky.social) in Jan 2027! #NewPI My lab will study the neurobiology of learning, memory, and motivation! 🧠🐭⚡️🔬

Michael Totty reposted

Replying to @martinowk.bsky.social

There are supp figures like these for all the blocks used - but, her ability to score and tile 6-8 pieces with minimal damage so the amygdala could be reconstructed is just 🙌

Michael Totty reposted

I am very excited to see this work out and so proud of @mictott.bsky.social & @svitlanabach.bsky.social! Study is a great example of moving beyond generating spatial transcriptomics data simply to generate molecular maps, to using the data to answer longstanding questions about human 🧠 organization.

Michael Totty@mictott.bsky.social

Incredibly proud to share our newest work where we developed a multiscale spatial transcriptomic atlas of the human amygdala using three complementary technologies! 1/12 🧵 www.biorxiv.org/content/10.6...

This was a huge team effort, so special shout out to the wet lab biologist who generated all of this data. Namely co-first author @svitlanabach.bsky.social, as well as Madeline Valentine and Sarah Maguire. Also huge thank you to other in the neuropath and neural plasticity teams here at LIBD.

This is a massive dataset and the first of it's kind, so I really was only able to scratch the surface of what insights it can provide. I'm excited to see how the community uses this resource, and for future projects in this space! 12/12

And we were able to discover considerable cell type heterogeneity in the central nucleus of the amygdala, revealing spatially distinct populations of PRKCD/PENK/CARPT vs SST/TAC3/CRH neurons that appear to resemble those found in mice CeA. 9/12

Finally, we wanted to ask how genetic risk for psychiatric disease localized within the human amygdala. gsMap revealed broad enrichment for brain-related traits in gray matter areas (in line with a highly polygenic architecture) whereas scDRS revealed nuclei specific enrichment. 10/12

This revealed that different amygdala nuclei contained completely distinct neuronal populations, and showed within nuclei heterogeneity such as the magnocellular and parvocellular divisions of the basal nucleus. 7/12

We next chose to use VisiumHD to provide full-transcriptome profiling at single cell resolution to characterize the intercalated cells and central nucleus. Combing this with reference atlases revealed at least 3 reproducible ITC cell types - two island and one non-island population. 8/12

Using the Xenium imaging-based technology, we were able to again reconstruct the known amygdala anatomy using a smaller targeted gene panel, while also providing validation for many novel marker genes at single cell resolution. 5/12

Several snRNA-seq references have recently been published describing the cell type diversity in the human amygdala. We were able to take these references (both Yu et al. and our previous dataset) and spatially map them into both our Visium and Xenium datasets. 6/12

Doing so allowed us to recover the known anatomy of the amygdala using unsupervised methods. This includes basolateral complex nuclei, medial and central nuclei, the cortical nucleus, and intercalated islands! As well as surrounding structures such as the hippocampus and claustrum. 3/12

Analyzing spatial co-expression networks allowed us to recover gene programs specific to distinct amygdala nuclei and identify core transcription factors that may play a central role in their molecular identity and function. 4/12

Our understanding of the molecular and cellular make up of the human amygdala has lagged far behind other structures. So we used Visium, Xenium, and VisiumHD to comprehensively profile the amygdala at full-transcriptome and single cell resolution across 9 total donors. 2/12

Michael Totty reposted

🧠🧬 What are the effects of intravenous fentanyl self-administration on the habenula and amygdala transcriptomes? In our new Addiction Biology paper, we addressed this question using a chronic long-access model in rats! Here are some highlights 🧵👇 Paper 👉 dx.doi.org/10.1111/adb....

dx.doi.orgTranscriptional Response to Chronic Long‐Access Fentanyl Self‐Administration in Rat Habenula and AmygdalaChronic intravenous long-access fentanyl self-administration in rats produced transcriptional remodeling in the habenula and amygdala. Bulk RNA-sequencing identified 453 habenula and 3,041 amygdala d...

Michael Totty reposted

Very excited about this new preprint from @odrake.bsky.social, an incredibly talented MD/PhD student in the lab. 🧵 below, but the TL;DR: we found a rare striatal neuron subtype with unique transcriptional, spatial, and circuit properties that gates opioid reward.

Olivia Drake@odrake.bsky.social

Our new preprint from @daylab.bsky.social characterizes Chst9-MSNs, a specialized NAc population with high Oprm1 expression and opioid sensitivity that is required for fentanyl reward learning. Excited to share this work! 🧠🧬 www.biorxiv.org/content/10.6...

Michael Totty reposted

Michael Totty reposted

Michael Totty reposted

Replying to @martinowk.bsky.social

I am very excited to continue working with @mictott.bsky.social thinking about translational potential of directly targeting this cell population, which continually remind us in dataset after dataset of their unique vulnerability across a number of neuropsych and neurodegenerative disorders!

Michael Totty reposted

Replying to @martinowk.bsky.social

Really nice thread from @mictott.bsky.social about the origin of the studies and the interpretation of the findings here when the preprint was posted: bsky.app/profile/mict...

Michael Totty@mictott.bsky.social

New paper out on cortistatin neurons and their role in regulating fear and cortical hyperexcitability in the prelimbic cortex! This one has been a fun ride 🧵 www.biorxiv.org/content/10.6...

Michael Totty reposted

Replying to @nicolecrust.bsky.social

I now have multifold confirmation: mouse studies at Janelia will wind down to be replaced by studies of fish. Wow.

Even with all the new imaging tech we have, nothing beats the old school neuroanatomy drawings. I particularly love the level of detail shown here of the various nuclei and cell types found in the human amygdala. Studies of the Vertebrate Telencephalon II. Crosby and Humphrey, 1941.

19 on my K99 resubmission! Massive thanks to my mentors and letter writers for all their support. Hard to tell if it will actually translate to funding in this climate, but I'll take the win regardless!

Fwiw, my initial submission was scored competitively (26) last August and it finally bumped to "Pending" 40+ days ago. Still no word, but maybe I'll get an NOA one of these days! I know others are in the same boat.