On the mechanisms of inferior olivary signalling : Timing, scaled impact and plasticity mechanisms exerted by the olivary spike

The inferior olive is regarded to be able to dictate activity in the cerebellum. Its spiking activity comprises the elusive complex spikes. In this dissertation we have looked into different putative roles of the complex spike. We have looked into a differential effect of the single complex spike based on its waveform (chapter one). The second chapter is on rhythmic firing of the complex spikes and whether such rhythmicity induces time conditional spiking to sensory stimulation. In the third chapter we have been looking into plasticity mechanisms influencing simple spike firing in the Purkinje neurons that are under controll of the complex spike activity patterns. In the fourth chapter we have been using calcium imaging to look at activity in multiple climbing fibers simultaneously. We tested whether climbing fibers responsive to different sensory modalities are anatomically organized in the cerebellar cortex

Quasiperiodic rhythms of the inferior olive

Inferior olivary activity causes both short-term and long-term changes in cerebellar output underlying motor performance and motor learning. Many of its neurons engage in coherent subthreshold oscillations and are extensively coupled via gap junctions. Studies in reduced preparations suggest that these properties promote rhythmic, synchronized output. However, the interaction of these properties with torrential synaptic inputs in awake behaving animals is not well understood. Here we combine electrophysiological recordings in awake mice with a realistic tissue-scale computational model of the inferior olive to study the relative impact of intrinsic and extrinsic mechanisms governing its activity. Our data and model suggest that if subthreshold oscillations are present in the awake state, the period of these oscillations will be transient and variable. Accordingly, by using different temporal patterns of sensory stimulation, we found that complex spike rhythmicity was readily evoked but limited to short intervals of no more than a few hundred milliseconds and that the periodicity of this rhythmic activity was not fixed but dynamically related to the synaptic input to the inferior olive as well as to motor output. In contrast, in the long-term, the average olivary spiking activity was not affected by the strength and duration of the sensory stimulation, while the level of gap junctional coupling determined the stiffness of the rhythmic activity i