On the Orchestration of Cerebellar Output

The aim of this thesis is to further quantify the temporal firing dynamics of Purkinje cells in relation to specific tasks, the spatial organization and orchestration of their activity as well as the impact of cerebellar output on downstream brain areas.
For this I will compare the behavioral learning abilities and Purkinje cell firing characteristics of a mouse mutant with impaired simple spike adaptation capabilities to its wild-types littermates in a whisker-based detection task. The involvement of the cerebellum in sensory perception and cognitive tasks (decision making) is key for this. Impairments of Purkinje cells result in degraded behavioral performance.
The direct correlation of temporal dynamics in Purkinje cell firing with behavior is presented in the conditioning of a reflex-loop. Both complex and simple spikes are correlated on a trial-by-trial basis with eyelid movements both during the execution of the conditioned behavior as well as over the course of its acquisition, revealing the intimate link in between them.
The dependence of spatial and temporal dynamics of complex spike activity on inferior olivary gap junctions is investigated. Different effects can be observed in complex spikes, that reflect the state of coupling between ensembles of olivary neurons. This study quantifies for the first time the impact of inferior olivary properties on Purkinje cell ensembles over a time range of multiple olivary oscillation cycles, which is potentially also essential for the function of the olivo-cerebellar loop.
Last, we analyze the participation of the cerebellum in absence seizures. Both Purkinje cell and cerebellar nuclei firing patterns are related to the seizure timing properties, showing on a cellular basis, that the cerebellum participates in absence seizures and how cerebellar stimulation can interrupt them.