Konopka Lab

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Decoding DNA sequence-driven evolution of the human brain epigenome at cellular resolution - Nature Communications How genetic changes prior to the human-chimpanzee split contributed to human brain evolution remains unknown. Here, the authors address this by identifying open-chromatin regions divergent in various ...

Revealing ancestral evolutionary patterns of the human brain at cell-type resolution, through comparative genomic analysis of open-chromatin regions across apes, old world monkeys & new world monkeys. New integrative paper from @konopkalab.bsky.social in @natcomms.nature.com. 🧠🧬🧪

Human CLOCK enhances neocortical function - Nature Neuroscience Regulation of gene expression is a facet of human brain specialization. Here, the authors show that human-like expression of the CLOCK gene in the mouse neocortex enhances cognitive flexibility and ne...

Human CLOCK enhances neocortical function @natneuro.nature.com @konopkalab.bsky.social @circadianclocks.bsky.social
www.nature.com/articles/s41...

We celebrated Haley graduating from the Neuroscience Ph.D. program at UT Southwestern. Huge congrats, Dr. Moore! 🎉🎓

Big news—we’ve moved to the David Geffen School of Medicine at UCLA! Even bigger: Gena is now Chair of the Department of Neurobiology. Congrats, Dr. Konopka! 💙🧠 #UCLA #Neurobiology #NewBeginnings

Thanks for the love! 🌟 Unfortunately, we don't have data from the ventral striatum at the moment, but who knows what the future holds? Always exciting to think about the possibilities! 😄

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🧪 Combining snRNA-seq + smFISH + cross-species comparisons + cross region comparisons = powerful insights into mammalian striatum evolution.

🧵Thanks for reading!

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Takeaways:
🧠 Our findings underscore the importance of including a diverse array of species and brain regions when uncovering novel cell types and examining cellular abundance variations which may lead to species-specific behaviors.

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We’re sharing the first snRNA-seq datasets from:
🐵 Chimpanzee CN (n=4) + Pu (n=6)
🦇 Bat (Phyllostomus discolor) CN + Pu (n=4 each)
Available to the neuroscience community! 🌍

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Uncovered species-specific differences in interneuron cell type abundance:
PDGFD PTHLH PVALB– interneurons = primarily found in primates 🐒
PDGFD PTHLH PVALB+ interneurons = primarily found in non-primates 🦇🐭🦦
Evolutionary divergence in PVALB expression within striatal interneurons!

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🦇 Having analyzed bat (Phyllostomus discolor) CN and Pu snRNA-seq separately we observed:
🔍 Significant neuron-to-glia ratio differences between CN and Pu.
📌2 novel bat interneuron types in Pu which may account for species-specific behavior:
🔹 LMO3 expressing
🔹 FOXP2 and TSHZ2 expressing

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🤯 Across ~94 million years of evolution, we found shared molecular markers for eccentric spiny neurons (eSPNs) in both primates 🐒 and non-primates 🐭🦦🦇.
These conserved markers suggest that eSPNs are a core striatal feature, as previously shown in mouse, not a recent innovation.

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Eccentric spiny neurons (eSPNs):
Found in lower proportions among SPNs in non-primates 🐭🦦🦇.
In primates, higher eSPN prevalence may support advanced cognitive functions and complex behaviors.
✅ Again, validated with smFISH. 🔬

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In primates, the CN shows lower neuron-to-glia ratios vs. non-primates.
This matches known allometric scaling of neuron density in larger brains
🧠 Bigger brains = ↓ neuron density but relatively stable glial density.
(See: Hirter et al. 2021, Herculano-Houzel 2014)
✅ Confirmed with smFISH. 🔬

We generated new snRNA-seq data from primates 🐒, and bats 🦇 as well as used other data from marmosets and non-primates 🐭🦦 from the caudate nucleus (CN) and putamen (Pu) (caudoputamen for mouse), uncovering fascinating differences in cell types and ratios. Let’s dive in! 👇

Evolution of the cellular landscape in mammalian striatum The dorsal striatum is important for highly specialized functions including movement, learning, and habit formation. However, it is not known if species-specialized behaviors are associated with cellu...

We are super excited to share our latest pre-print in collaboration with @sonjavernes.bsky.social lab! www.biorxiv.org/content/10.1... : Evolution of the cellular landscape in mammalian striatum 🧠🧬🧵

Hi Cedric! Thank you for highlighting our work! Stay posted for more cool studies from our lab!

Evolution of the cellular landscape in mammalian striatum The dorsal striatum is important for highly specialized functions including movement, learning, and habit formation. However, it is not known if species-specialized behaviors are associated with cellu...

Very nice comparative study by the labs of Gena Konopka & Sonja Vernes, on the evolution of the cellular landscape in mammalian striatum 🧪🧠🧬
www.biorxiv.org/content/10.1...