Differential chemoarchitecture of Purkinje neurons within cerebellar lobules contributes to intrinsic plasticity: Significance for autism spectrum disorders

Abstract

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 insights into what underlies the divergence in firing parameters. Although long used as a general PC marker, here it is reported that the calcium binding protein parvalbumin labels a subpopulation of PCs with a conserved distribution pattern, similar to aldolase C. A convolutional neural network was trained to recognize the parvalbumin-positive subtype and create maps of whole cerebellar distribution. PCs within these areas have differences in spontaneous firing that can be modified by altering calcium buffer content, which implicates parvalbumin in setting the spike rate and contributing to burst-pause behavior. These subtypes also show differential responses to potassium and calcium channel blockade, suggesting a mechanistic role for variability in PC intrinsic firing. These findings open new avenues for detailed classification of PC subtypes and prompt further investigation into determining which subtype(s) are affected by the reported PC decreases within human postmortem autism brain tissue. Part 2 explores serotonin, GABA and dopamine in cortical regions and the basal ganglia in the human postmortem autism brain to quantify differences in receptor subtypes.