Transcriptomic mapping uncovers Purkinje neuron plasticity driving learning.

TitleTranscriptomic mapping uncovers Purkinje neuron plasticity driving learning.
Publication TypeJournal Article
Year of Publication2022
AuthorsChen, X, Du, Y, Broussard, GJoey, Kislin, M, Yuede, CM, Zhang, S, Dietmann, S, Gabel, H, Zhao, G, Wang, SS-H, Zhang, X, Bonni, A
JournalNature
Volume605
Issue7911
Pagination722-727
Date Published2022 05
ISSN1476-4687
KeywordsAnimals, Cerebellum, Learning, Mice, Mice, Knockout, Neuronal Plasticity, Neurons, Purkinje Cells, Transcriptome
Abstract

<p>Cellular diversification is critical for specialized functions of the brain including learning and memory. Single-cell RNA sequencing facilitates transcriptomic profiling of distinct major types of neuron, but the divergence of transcriptomic profiles within a neuronal population and their link to function remain poorly understood. Here we isolate nuclei tagged 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 gene expression in mice subjected to sensorimotor and learning experience. In vivo calcium imaging and optogenetic perturbation reveal that Plcb4 Purkinje neurons have a crucial role in associative learning. Integrating single-nucleus RNA sequencing datasets with weighted gene co-expression network analysis uncovers a learning gene module that includes components of FGFR2 signalling in Plcb4 Purkinje neurons. Knockout of Fgfr2 in Plcb4 Purkinje neurons in mice using CRISPR disrupts motor learning. Our findings define how diversification of Purkinje neurons is linked to their responses in motor learning and provide a foundation for understanding their differential vulnerability to neurological disorders.</p>

DOI10.1038/s41586-022-04711-3
Alternate JournalNature
PubMed ID35545673
Grant ListR01 NS041021 / NS / NINDS NIH HHS / United States
R01 NS045193 / NS / NINDS NIH HHS / United States
R01 MH115750 / MH / NIMH NIH HHS / United States