Motor and non-motor control by neuronal subpopulations within the deep cerebellum
Low, Aloysius Yeow Teck
Date of Issue2018-12-31
Interdisciplinary Graduate School (IGS)
The cerebellum is linked to a multitude of regions in the brain and spinal cord, projecting to at least twenty-seven brain regions, to control a diverse array of motor and non-motor processes. Embedded within lies the cerebellar nuclei which receive, integrate and transmit diverse sensorimotor information to relevant brain regions. However, the functional relevance of identifiable neuronal subpopulations within the cerebellar nuclei remains unclear. To explore the mechanisms underlying the function of the cerebellar nuclei, we examined a subset of genetically tractable neurons in the mouse cerebellar interposed nucleus, and studied the involvement of these neurons in discrete and rhythmic limb movements, and in feeding-related tasks. Analysis of the connectivity and function of these neurons through tract tracing and optogenetic experiments revealed that a subset of glutamatergic neurons in the anterior cerebellar interposed nucleus can be labeled with the Urocortin 3::Cre mouse line, and that these neurons constitute a specific element of an internal feedback circuit within the cerebellum and cerebello-thalamo-cortical pathway associated with limb control. Additionally, through trans-synaptic and anterograde/retrograde tracing analysis, we found that neurons in the interposed nucleus also belong to the cerebello-subthalamic-hypothalamic pathway which may be involved in non-motor processes. Chemogenetic manipulation of neurons in the interposed nucleus revealed that the activity of neurons in the arcuate nucleus and feeding behavior also depend on neurons in the interposed nucleus. In summary, we show that target selectivity may be a key distinguishing property among neuronal subpopulations in the cerebellar nuclei, and illustrate the diversity and complexity of intra- and extra-cerebellar connections made by neurons in the cerebellar nuclei. In agreement with the notion that the cerebellum modulates both motor and non-motor functions, our study links different subpopulations of glutamatergic neurons in the interposed nucleus and their unique circuitry with coordination of precise and effective movements, as well as mediation of feeding-related response.