Sodium Channels and Plasticity in Cerebellar Networks

Scientists have attempted to unravel how the highly plastic cerebellum combines the information it receives, integrates it, and adjusts its synaptic strength accordingly, from the single cell to the behavioural level. With some exceptions most of the knowledge we have about the cerebellum comes from studying the mammalian cerebellum. Some questions that until now remain open may be answered better by comparing these data with studies in other animal groups. In a large part of this thesis the rat cerebellum will be compared with that of mormyrid fish. In chapter 2 cerebellar voltage-gated sodium channels are investigated. This chapter studies the expression patterns of sodium channel α-subunits, the currents carried by these channels and the role dendritic tree architecture plays in shaping sodium currents upon climbing fiber stimulation in rat and mormyrid fish cerebellum. Chapter 3 investigates backpropagation of spikes in interneurons of the mormyrid ele! ctrosensory lateral line lobe (ELL). This chapter, like chapter 2, studies voltage gated sodium channels. The focus of chapter 3, however, is on backpropagating spikes in the dendritic arborisation of the ELL interneurons. Anti-Hebbian plasticity in the ELL depends on the generation of backpropagating spikes. Chapter 4 studies another intracellular factor involved in cerebellar plasticity. This chapter focuses on the role of CRF in regulating excitatory transmission and LTD at the climbing fiber-Purkinje cell synapse of rat cerebellar slices. Chapter 5 studies cerebellar plasticity at the in vivo level in mice that have been genetically deprived of vestibular input.