Anterograde Viral Tracing of Projections from Vermal Lobule VI of the Mouse Cerebellar Cortex

Abstract

Most research into cerebellar function and connectivity is with regard to its role in motor function, but the cerebellum is also involved in a wide range of cognitive and affective domains. The posterior vermis of the cerebellar cortex in particular is functionally linked to language, memory, cognitive control, and emotion, but the structural connections that could underlie this role in the cerebellum are poorly researched. Here we examine vermal lobule VI for projections to the neocortex and other areas associated with non-motor function. Using trans-synaptic primarily anterograde viral tracing with herpes simplex virus 1 strain H129, we can investigate the pathways from the cerebellar cortex out to the rest of the brain.

Additionally, by using a virus containing the Brainbow cassette, we demonstrate a method for using conditional fluorescent reporters to disambiguate different neural pathways that could otherwise be indistinguishable in tracing studies. We found viral spread to cortical and subcortical areas including the anterior cingulate cortex, hippocampus, and dorsal thalamus, areas closely linked to functions such as memory, emotional regulation, and social function. These experiments show evidence for projections from cerebellar lobule VI to areas of the brain involved in complex, higher-level processing, providing a possible anatomical mechanism for lobule VI specifically and the cerebellum more generally to be involved in cognition and emotion.