On the mechanisms of inferior olivary signalling

Date: 25 April 2017

Venue: Erasmus MC Rotterdam, The Netherlands

Time: 3:30 PM - 5:30 PM

PhD candidate: Pascal Warnaar

Principal investigator: Erik De Schutter, Chris de Zeeuw

Short description: PhD defence Pascal Warnaar - Department of Biomedical Sciences


The inferior olive exerts great impact on the cerebellum and is considered to set cerebellar function. The olivary neurons send out low frequency signals, which trigger elaborate voltage patterns the so-called complex spikes in the downstream Purkinje neurons. The complex spikes have been linked to set cerebellar functioning, by means of controlling simple spike firing in the Purkinje neurons. Long term depression of simple spike firing is the mechanism that is at the core of the error correction theory exerted by the cerebellum. The absence however of conclusive experimental results on crucial hypotheses have led to speculations on the role of the complex spikes. In this dissertation we have studied mechanisms of the inferior olive so to test some of the most prominent theories on the role of the inferior olive.

A conspicuous feature of the inferior olivary neurons is its subthreshold membrane potential oscillation, which were found stable in in vitro recordings. Through phase dependent spiking these oscillations can set firing patterns and finds support in in vivo spiking patterns, entrainment and tremor data. We addressed the question; does the inferior olivary activity allow for ‘rhythmic’ pattern formation in the cerebellum and hence set timing properties derived from these rhythms? We combined in vivo results with theoretical testing in computational models to test for our assumptions.

The error correction theory assumes the inferior olivary to send out an error signal. However in vivo results do not fully support this theory. The elaborate waveform seen in the complex spike could potentially underlie a somewhat overlooked layer of information in the signal, explaining for example why olivary spiking is not restricted to clear error signals. In this study we describe the complex spike signals observed in awake monkeys and test whether these shapes relate to behavioral characteristics.

We furthermore studied the control exerted by the complex spike on potentiation of the simple spike firing. The results on spike dynamic interactions were tested for effects on behavioral changes as observed in whisker movements.

The inferior olivary neurons readily respond to sensory stimulation. The structured alignment of purkinje neurons in the cerebellar cortex can underly a sensory map. By recording multiple Purkinje neurons simultaneous and testing different sensory stimuli we analyzed if inferior olivary neurons respond to multiple sensory modalities, and if so do these response patterns show pattern generalities?

Link: https://www.uantwerpen.be/en/faculties/fbd/research/public-defence-of-a-phd/