A Podcast episode based on my doctoral publication

The paper explores the selective vulnerability of layer 5a corticostriatal neurons in Huntington's disease (HD). We used a novel technique called serial fluorescence-activated nuclear sorting (sFANS) to isolate and analyze different cell types from the cerebral cortex of HD patients.

What we found was surprising, layer 5a neurons, which project to the striatum, are particularly vulnerable in HD, while other deep layer neurons remain relatively resilient. The study also revealed that extensive somatic expansion of the mHTT CAG repeat occurs in both vulnerable and resilient neurons, suggesting that this expansion alone may not be the primary cause of cell death. In addition, our data suggest that altered synaptic function and disruption of corticostriatal connectivity may play a significant role in the selective vulnerability of layer 5a neurons in HD.

Pressl, C., Mätlik, K., Kus, L., Darnell, P., Luo, J. D., Paul, M. R., … Heintz, N. (2024). Selective vulnerability of layer 5a corticostriatal neurons in Huntington’s disease. Neuron, 112(6), 924-941.e10. https://doi.org/10.1016/j.neuron.2023.12.009

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