Disynaptic cerebrocerebellar pathways originating from multiple functionally distinct cortical areas

Julia U Henschke,Janelle Mp Pakan

doi:10.7554/elife.59148

Abstract

The cerebral cortex and cerebellum both play important roles in sensorimotor processing, however, precise connections between these major brain structures remain elusive. Using anterograde mono-trans-synaptic tracing, we elucidate cerebrocerebellar pathways originating from primary motor, sensory, and association cortex. We confirm a highly organized topography of corticopontine projections in mice; however, we found no corticopontine projections originating from primary auditory cortex and detail several potential extra-pontine cerebrocerebellar pathways. The cerebellar hemispheres were the major target of resulting disynaptic mossy fiber terminals, but we also found at least sparse cerebrocerebellar projections to every lobule of the cerebellum. Notably, projections originating from association cortex resulted in less laterality than primary sensory/motor cortices. Within molecularly defined cerebellar modules we found spatial overlap of mossy fiber terminals, originating from functionally distinct cortical areas, within crus I, paraflocculus, and vermal regions IV/V and VI - highlighting these regions as potential hubs for multimodal cortical influence.

Highlights

The environment provides constantly updating sensory signals that must be acted upon for an animal to perform basic behaviors necessary for survival, including navigating through the environment, feeding/foraging, and other goal-directed behaviors
To examine the topography of cerebrocerebellar pathways from primary sensory and motor cortical regions as well as sensory association areas, we utilized an AAV1.cre construct that has been shown to act as a trans-synaptic anterograde tracer that crosses a single functional synapse
Anterogradely labeled cell bodies were not observed in the pontine nuclei following AAV1.cre injections in A1, labeled fibers were found in the dorsomedial portion of the ipsilateral pons (Figure 1E; Supplementary file 1B). These fibers could be either traversing through the pons, potentially towards lower brainstem structures, or disynaptic terminals resulting from labeled indirect pathways from A1 to the pontine nuclei, likely via the inferior colliculus (Schuller et al, 1991b; Caicedo and Herbert, 1993)

Summary

Introduction

The environment provides constantly updating sensory signals that must be acted upon for an animal to perform basic behaviors necessary for survival, including navigating through the environment, feeding/foraging, and other goal-directed behaviors These perception and action loops require various sensory modalities (i.e. somatosensation, audition, and vision) to be integrated and translated into directed motor output. Both the cerebral cortex (Stein and Stanford, 2008) and the cerebellum (Snider and Stowell, 1944; Rondi-Reig et al, 2014; Baumann et al, 2015) are major brain regions involved in this sensorimotor integration and translation Connections between these two brain regions form one of the largest projection pathways in the brain and selective expansion of this cortico-cerebellar system occurs across evolution (Gutierrez-Ibanez et al, 2018; Smaers and Vanier, 2019). A vital initial step in understanding the role of cerebrocerebellar communication is to have a comprehensive map of the pathways linking these two structures as well as the precise organization of the termination of these pathways within the cerebellum

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Conclusion