Anatomical and Functional Study of the Superior Colliculus Pathway to the Inferior Olive in Mice

Abstract

Okinawa Institute of Science and Technology Graduate UniversityDoctor of PhilosophyThe Inferior olive is an important region for motor learning and movement coordination. Its climbing fiber projections to Purkinje neurons drive complex spike activity, a central element in cerebellar function theories. Although the function of the inferior olive has been investigated by the occurrence of complex spikes during motor learning, it remains unclear how its intrinsic properties and activity shape the generation of complex spikes upon receiving sensory stimulation. To investigate how signals from a pre-olivary structure with a well-defined behavioral role affect IO spiking, I focused on an afferent from the midbrain superior colliculus. The superior colliculus is an evolutionarily conserved midbrain region known for its role in mediating orienting-related movements. The SC-IO pathway serves as an excellent model for studying how inferior olive neurons (IO) respond to their inputs. Additionally, this pathway raises the exciting possibility for orienting-related behaviors modulated by learning through the olivo-cerebellar system. In this study, we explore SC projections to the IO using viral tracers, calcium imaging, and optogenetic stimulation. In addition to the established projections to the medial accessory olive (MAO), we uncover SC axonal projections to the ventral principal olive (PO). Our findings reveal that SC axons terminate on both dendritic shafts and spines of IO neurons, potentially influencing the probability of spike and the network synchronization mediated by gap junctions on dendritic spines. To demonstrate the ability of SC axons to drive IO spiking, we performed in vivo calcium imaging and showed that optogenetic activation of SC inputs not only induces spiking, but also modulates the overall synchronization of the IO. This study lays a foundational framework for exploring the behavioral relevance of the SC-IO pathway in mice.doctoral thesi