Scientists have created a detailed, cell-by-cell map of the striatum — a deep brain region that governs movement, decision-making, habits and reward, and is implicated in Huntington’s disease, schizophrenia, depression and addiction.
Researchers at MIT, led by Prof. Myriam Heiman, analyzed 109 human and 22 mouse postmortem samples using single-nucleus RNA sequencing and spatial mapping. The resulting atlas identified 31 neuronal subpopulations — including nine types of “medium spiny neuron” never classified before. The work was published in Cell.
Which cells disease targets
The map pinpointed disease-vulnerable populations. Some neurons (“D1 outliers”) strongly expressed genes tied to substance use disorder, including opioid-response genes; others (“D2 outliers”) expressed genes involved in antidepressant response. And in the dorsal striatum, certain neurons showed elevated MSH2/MSH3 genes that accelerate the toxic CAG-repeat expansion of Huntington’s disease — helping explain why those cells are hit hardest.
Why it matters
One striking finding: the human mu-opioid receptor gene OPRM1 was highly active in human neurons but not the matching mouse cells — a warning that standard rodent models may not fully capture human addiction. Maps like this “lay the foundation for understanding how striatal cell types…contribute to…neurological disorders,” Heiman said — a resource researchers can mine to design more precisely targeted treatments.