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 channe

GATA3 haploinsufficiency causes a rapid deterioration of distortion product otoacoustic emissions (DPOAEs) in mice

Human HDR (hypoparathyroidism, deafness and renal dysplasia)-syndrome is caused by haploinsufficiency of zinc-finger transcription factor GATA3. The hearing loss due to GATA3 haploinsufficiency has been shown to be peripheral in origin, but it is unclear to what extent potential aberrations in the outer hair cells (OHCs) contribute to this disorder. To further elucidate the pathophysiological mechanism underlying the hearing defect in HDR-syndrome, we investigated the OHCs in heterozygous Gata3-knockout mice at both the functional and morphological level. While the signal-to-noise ratios of distortion product otoacoustic emissions (DPOAE) in wild type mice did not change significantly during the first half-year of live, those in the heterozygous Gata3 mice decreased dramatically. In addition, both light microscopic and transmission electron microscopic analyses showed that the number of OHCs containing vacuoles was increased in the mutants. Together, these findings indicate that outer hair cell malfunctioning plays a major role in the hearing loss in HDR-syndrome

Voltage-gated sodium channels in cerebellar Purkinje cells of mormyrid fish

Cerebellar Purkinje cells of mormyrid fish differ in some morphological as well as physiological parameters from their counterparts in mammals. Morphologically, Purkinje cells of mormyrids have larger dendrites that are characterized by a lower degree of branching in the molecular layer. Physiologically, there are differences in electrophysiological response patterns that are related to sodium channel activity: first, sodium spikes in mormyrid Purkinje cells have low amplitudes, typically not exceeding 30 mV. Second, the response to climbing fiber sti

Alcohol impairs long-term depression at the cerebellar parallel fiber-Purkinje cell synapse

Acute alcohol consumption causes deficits in motor coordination and gait, suggesting an involvement of cerebellar circuits, which play a role in the fine adjustment of movements and in motor learning. It has previously been shown that ethanol modulates inhibitory transmission in the cerebellum and affects synaptic transmission and plasticity at excitatory climbing fiber (CF) to Purkinje cell synapses. However, it has not been examined thus far how acute ethanol application affects long-term depression (LTD) and long-term potentiation (LTP) at excitatory parallel fiber (PF) to Purkinje cell synapses, which are assumed to mediate forms of cerebellar motor learning. To examine e