Convergence of pontine and proprioceptive streams onto multimodal cerebellar granule cells

Cerebellar granule cells constitute the majority of neurons in the brain and are the primary conveyors of sensory and motor-related mossy fiber information to Purkinje cells. The functional capability of the cerebellum hinges on whether individual granule cells receive mossy fiber inputs from multiple precerebellar nuclei or are instead unimodal; this distinction is unresolved. Using cell-type-specific projection mapping with synaptic resolution, we observed the convergence of separate sensory (upper body proprioceptive) and basilar pontine pathways onto individual granule cells and mapped this convergence across cerebellar cortex. These findings inform the long-standing debate about the multimodality of mammalian granule cells and substantiate their associative capacity predicted in the Marr-Albus theory of cerebellar function. We also provide evidence that the convergent basilar pontine pathways carry corollary discharges from upper body motor cortical areas. Such merging of related corollary and sensory streams is a critical component of circuit models of predictive motor control. DOI: http://dx.doi.org/10.7554/eLife.00400.001
eLife digest Learning a new motor skill, from riding a bicycle to eating with chopsticks, involves the cerebellum—a structure located at the base of the brain underneath the cerebral hemispheres. Although its name translates as ‘little brain' in Latin, the cerebellum contains more neurons than all other regions of the mammalian brain combined. Most cerebellar neurons are granule cells which, although numerous, are simple neurons with an average of only four excitatory inputs, from axons called mossy fibers. These inputs are diverse in nature, originating from virtually every sensory system and from command centers at multiple levels of the motor hierarchy. However, it is unclear whether individual granule cells receive inputs from only a single sensory source or can instead mix modalities. This distinction has important implications for the functional capabilities of the cerebellum. Now, Huang et al. have addressed this question by mapping, at extremely high resolution, the projections of two pathways onto individual granule cells—one carrying sensory feedback from the upper body (the proprioceptive stream), and another carrying motor-related information (the pontine stream). Using a combination of genetic and viral techniques to label the pathways, Huang and co-workers identified regions where the two types of fiber terminated in close proximity. They then showed that around 40% of proprioceptive granule cells formed junctions, or synapses, with two (or more) fibers carrying different types of input. These cells were not uniformly distributed throughout the cerebellum but tended to occur in ‘hotspots’. Lastly, Huang et al. examined the type of information conveyed by the sensory and motor-related input streams whenever they contacted a single granule cell. They confirmed that when the sensory input consisted of feedback from the upper body, the motor input consisted of copies of motor commands related to the same body region. Because it is thought that the cerebellum converts sensory information into representations of the body's movements, directing motor commands to these same circuits may allow the cerebellum to predict the consequences of a planned movement prior to, or without, the actual movement occurring. The work of Huang et al. provides evidence to support the previously controversial idea that granule cells in the mammalian cerebellum receive both sensory and motor-related inputs. The labeling technique that they used could also be deployed to study the inputs to the cerebellum in greater detail, which should yield new insights into the functioning of this part of the brain. DOI: http://dx.doi.org/10.7554/eLife.00400.002