Cerebellar Purkinje cells change dendritic architecture during primate evolution

Abstract

Vertebrate evolution has driven adaptive remodeling of brain regions impacted by changing sensorimotor demands. The cerebellum--a hindbrain area mediating associative learning and predictive coding--is thought to participate in diverse motor and non-motor behaviors across vertebrate species by duplicating and repurposing a conserved cortical circuit. Yet, few studies systematically compare circuit architecture across cerebellar evolution. We recently found that human Purkinje cells (PCs, the principal neuron of the cerebellar cortex) almost universally have multiple primary dendrites, a structural motif that confers distinct signaling properties, as shown by experiments in mice where this motif is present but less common. Seeking evolutionary insight, we developed a framework to parameterize and compare PC morphology across 11 simiiform (anthropoid) primates representing 40 million years of evolution, and mice as an outgroup. Dendritic architecture shifts profoundly from single primary dendrites with vertical orientation in mice and monkeys to multiple horizontally oriented primary dendrites in apes and, particularly pronounced, in humans. Increasing dendritic compartmentalization in the human lineage is produced by monotonic, stepwise, or human-specific trends across individual morphological traits. PC morphology is high-dimensional, with most features varying widely and independently, yet clade identity can be readily predicted from multivariate morphospace profiles. Phylogenetic patterns are not well explained by tissue foliation or allometric scaling, supporting the hypothesis that morphological variation is constrained by functional demands. Echoing a core principle of brain evolution that selection pressure drives fine-tuning of circuit elements rather than total circuit rearrangement, PC dendrite morphology may serve as a key node for cerebellar adaptation amid a conserved circuit architecture.