Understanding the Mechanisms of Motor Learning in the Vestibulo-ocular Reflex

The vestibulo-ocular reflex (VOR) is a simple reflex that stabilizes gaze by moving the eyes in the opposite direction to the head. The gain of the VOR (ratio of head to eye velocity) can be increased or decreased during motor learning. It is thought that the memory for learned changes in the VOR gain is initially encoded within the cerebellar flocculus. Furthermore, these learned gain changes can be disrupted or consolidated into a long-term memory. In this thesis we describe novel results that show that consolidation of the VOR can take place rapidly, within 1 hour after learning has stopped. Furthermore, we demonstrated that unlike learning, which has been shown to have frequency selectivity, disruption and rapid consolidation generalize across the range of frequencies. We suggest that disruption and rapid consolidation in the VOR are local mechanisms within the cerebellar cortex, and do not require new learning. This thesis also provides additional evidence for the idea that learned gain increases and decreases are the result of separate mechanisms, most likely long-term depression and potentiation respectively, at the parallel fibre-Purkinje cell synapses. We demonstrate that learned gain increases, but not decreases, require the activation of type 1 metabotropic glutamate receptors (mGluR1) and B type γ-aminobutyric acid (GABAB) receptors. Blocking one or both of these receptors with an antagonist inverts gain-up learning, while the agonist augments gain-up learning. Furthermore, we provide novel evidence that these receptors are co-activated during gain-up learning.Ph