Distal influences of cerebellum-specific tuberous sclerosis on dendritic spines in the prefrontal cortex

Abstract

The role of the cerebellum in cognitive processes through cerebello-thalamo-cortical loops has been increasingly established in recent decades. In this thesis, a Purkinje cell-specific tuberous sclerosis (Tsc1) mutation in mice is used to study the effect of reduced Purkinje cell excitability, and thus cerebellar disruption throughout development and adulthood, on dendritic spine characteristics in the medial prefrontal cortex (mPFC). To do so, cortical tissue was labeled using the diolistic labeling technique and imaged; dendrites and spines were reconstructed to analyze mature (spine length ≤ 1 μm), immature (spine length > 1 μm), and total (sum of immature and mature spines) dendritic spine density for apical and basal dendrites of pyramidal neurons in layers II and III of the mPFC. Increases in total dendritic spine density and immature dendritic spine density were found for basal dendrites in heterozygous mutant animals. These findings indicate a causative role for the cerebellum in basal dendritic spine density of mPFC pyramidal neurons and thus proposed to play a role in synaptic efficiency and cognition in this region. Future research will further specify the nature of this effect and how it mechanistically develops through precise pathways during development as well as identify lobule-specificity of the cerebellum’s role in mPFC dendritic spine characteristics.