Topological mapping of polysynaptic projections from cerebellar vermis to nonmotor areas using transsynaptic viral tracing

Abstract

The cerebellum, classically involved with motor coordination, is known to act as a perceptron to correct motor errors and refine movement. However, growing evidence for a nonmotor, behavioral role or the cerebellum comes in part from clinical observations following cerebellar damage and tracing studies that have linked the cerebellum to other cognitive and affective brain regions. In order to understand the nature of these pathways, the research outlined here seeks to investigate the neuronal connectivity and topography of nonmotor projections from the cerebellum’s vermal lobule VI—an area explicitly associated with autism spectrum disorder (ASD) when damaged. Viral tracing allows these connections to be probed transsynpatically in mouse models. Nine focal injections of anterograde-acting herpes simplex virus (HSV) H129 were administered at various coordinates across the vermal lobule VI and forebrain and midbrain projections were recorded. It was found that nearly all mediolateral areas project bilaterally to the deep cerebellar nuclei, and that different injection sites projected variably to different regions. Using this data and post-hoc data regarding true injection site spread, we were able to build a topographical map of projections from the vermal lobule VI to the following nonmotor areas: the laterodorsal nucleus of the thalamus, the parafascicular nucleus of the thalamus, the ventral tegmental area, the striatum, and the nucleus accumbens, mediodorsal nucleus of the thalamus, the hypothalamus, and the amygdala. The topography both confirms nonmotor connectivity of lobule VI and suggests possible sources of cerebellar-related nonmotor dysfunction.