Abstract

The cortico-cerebellar circuits are highly involved in the coordination of sensorimotor processes and are crucial for the expression of sensorimotor and, with more recent literature, cognitively demanding behaviors in early childhood. Through these circuits, cerebellar differences could impact behavioral changes characterized in many neurological disorders, including Autism Spectrum Disorder (ASD). Despite the increasing prevalence of the disorder, insights into the anatomical differences across cerebellar neuronal networks in ASD remain poorly understood. The objective of this thesis is to characterize the cerebellar circuitry in a valproic acid (VPA)-induced animal model of ASD. Tissues were stained with Cresyl violet and captured with a confocal microscope. First, we examined the counts in (1) Purkinje cell (PC) and (2) Deep cerebellar nuclei (DCN) cells while measuring their density. Consistent with our hypothesis, we found that there were: (1) significant losses in PC density in the posterior inferior regions of lobules Crus I, Crus II, PM, and Cop of the hemisphere, and (2) significantly higher DCN density of the medial nuclei, contrary to our hypothesis, in the VPA-exposed rats compared to the control. Then, we examined the granule cell layer (GCL) thickness measurements across the lobules of the vermis and hemisphere and found that GCL thickness of Lobule 6 was lower, while Lobule 7-8-9 and Lobule 10 were higher in the VPA-exposed rats compared to control. Finally, we found a correlation and cross-covariance between the PC and GCL thickness measurements in the lobules of the posterior lobe. These findings suggest alterations in cerebellar anatomy affected by the VPA, and therefore further support the implication of the cerebellum and cerebellar circuits in VPA-exposed rats.