biostudies-literatureChen XNIMH NIH HHSNINDS NIH HHS722-727https://www.ebi.ac.uk/biostudies/studies/S-EPMC9887520biostudies-literatureUnknown605(7911)Cellular diversification is critical for specialized functions of the brain including learning and memory¹. Single-cell RNA sequencing facilitates transcriptomic profiling of distinct major types of neuron^2-4, but the divergence of transcriptomic profiles within a neuronal population and their link to function remain poorly understood. Here we isolate nuclei tagged⁵ in specific cell types followed by single-nucleus RNA sequencing to profile Purkinje neurons and map their responses to motor activity and learning. We find that two major subpopulations of Purkinje neurons, identified by expression of the genes Aldoc and Plcb4, bear distinct transcriptomic features. Plcb4⁺, but not Aldoc⁺, Purkinje neurons exhibit robust plasticity of geneNatureTranscriptomic mapping uncovers Purkinje neuron plasticity driving learning.PMC9887520F32 MH120887R01 NS041021R01 NS045193R01 MH115750Gabel HBroussard GJZhang XZhao GDu YYuede CMChen XBonni AZhang SDietmann SWang SSKislin MfalseTranscriptomic mapping uncovers Purkinje neuron plasticity driving learning.Cellular diversification is critical for specialized functions of the brain including learning and memory¹. Single-cell RNA sequencing facilitates transcriptomic profiling of distinct major types of neuron^2-4, but the divergence of transcriptomic profiles within a neuronal population and their link to function remain poorly understood. Here we isolate nuclei tagged⁵ in specific cell types followed by single-nucleus RNA sequencing to profile Purkinje neurons and map their responses to motor activity and learning. We find that two major subpopulations of Purkinje neurons, identified by expression of the genes Aldoc and Plcb4, bear distinct transcriptomic features. Plcb4⁺, but not Aldoc⁺, Purkinje neurons exhibit robust plasticity of gene2022-01-01T00:00:00Z2022 May2025-04-05T16:07:04.185Z2025-04-05T16:07:04.185ZS-EPMC98875203554567310.1038/s41586-022-04711-3