RT Journal Article SR Electronic T1 Differential chemoarchitecture of Purkinje neurons contributes to intrinsic firing properties JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.01.28.428615 DO 10.1101/2021.01.28.428615 A1 Cheryl Brandenburg A1 Lindsey A. Smith A1 Michaela B.C. Kilander A1 Morgan S. Bridi A1 Yu-Chih Lin A1 Shiyong Huang A1 Gene J. Blatt YR 2021 UL http://biorxiv.org/content/early/2021/01/28/2021.01.28.428615.abstract AB Purkinje cells (PCs) are central to cerebellar information coding and appreciation for the diversity of their firing patterns and molecular profiles is growing. Heterogeneous subpopulations of PCs have been identified that display differences in intrinsic firing properties without clear mechanistic insight into what underlies the divergence in firing parameters. Although long used as a general PC marker, we report that the calcium binding protein parvalbumin labels a subpopulation of PCs with a conserved distribution pattern across the animals examined. We trained a convolutional neural network to recognize the parvalbumin-positive subtype and create maps of whole cerebellar distribution and find that PCs within these areas have differences in spontaneous firing that can be modified by altering calcium buffer content. These subtypes also show differential responses to potassium and calcium channel blockade, suggesting a mechanistic role for variability in PC intrinsic firing through differences in ion channel composition. It is proposed that ion channels drive the diversity in PC intrinsic firing phenotype and parvalbumin calcium buffering provides capacity for the highest firing rates observed. These findings open new avenues for detailed classification of PC subtypes.Competing Interest StatementThe authors have declared no competing interest.