Investigating the Divergence of Cerebellar Modules using Transsynaptic Viral Tracing and High Throughput Whole Brain Imaging

Abstract

The cerebellum plays an important role in motor and cognitive functions. In addition, cerebellar abnormalities are strongly associated with developmental disorders such as autism spectrum disorder. To understand the role of the cerebellum in these disorders it is important to first have a strong understanding of how the cerebellum is organized in its typical state. Decades of research has shown that cerebellar computations occur within parallel modules. However, the extent to which these modules are closed off from other modules has not been studied in depth. In this thesis, we applied modern transsynaptic tracers and high throughput whole brain imaging to see if modules form closed circuits. To do this, we performed a novel disynaptic tracing experiment using Herpes Simplex Virus (HSV)-129 ∆TK-TT and analyzed disynaptic projection patterns in previously collected HSV-129 and Pseudorabies virus (PRV)-Bartha datasets. Convergent evidence across these three experimental approaches indicate that disynaptic projections diverge from what would be predicted if modules were completely closed. Together these findings suggest that cerebellar circuits are not entirely closed on a modular level. In summary, this work clarifies the degree of divergence in the cerebellar trisynaptic loop and contributes to imaging, viral, and annotation approaches for anatomical probing of

cerebellar circuitry.