Axonal propagation of action potentials in cerebellar Purkinje
Doctoral thesis, UCL (University College London).
Electrical signals are the basis of information processing in the nervous system. Action potentials (APs), the output signals of neurons, are generated in and propagate along the axon to transmit information to downstream neurons. Identifying where in the axon APs are initiated and how they propagate throughout the axonal arbour is critical to understanding neuronal function. This thesis addresses these questions for the Purkinje cell (PC) axon, the sole output route of the cerebellar cortex. Using combined whole-cell patch clamp and multisite recordings of extracellular APs (eAPs) from PCs in mouse cerebellar slices, I present evidence that PC APs are initiated close to the soma, at the axon initial segment. With the help of theoretical modelling I show that eAP recordings are a valid method for identifying the axonal AP initiation site. Besides long-range projections to the deep cerebellar nuclei (DCN), PCs also innervate neurons of the cerebellar cortex via recurrent axon collaterals. I present data showing that simple spikes propagate reliably even at high frequencies (250 Hz) into recurrent axon collaterals of PCs of mature and young animals, whereas complex spikes fail to propagate fully. This is comparable to previous reports of propagation along the main axon and suggests that PC axons relay information similarly between the DCN and the local network. PCs express axonal voltage-gated Ca2+ channels (VGCC) early in postnatal development, but their role post-myelination is unknown. I demonstrate spatially-restricted activity-dependent Ca2+ influx at branch points of PC axons, which are typically nodes of Ranvier. I show that baseline nodal [Ca2+] depends on spontaneous firing frequency, suggesting that nodal [Ca2+] reports neuronal activity. Finally, I present data demonstrating that blockade of nodal VGCCs reduces axonal spike propagation velocity and can lead to propagation failure, showing that nodal VGCCs are crucial to facilitate and safeguard axonal spike propagation.
|Title:||Axonal propagation of action potentials in cerebellar Purkinje cells|
|Additional information:||Permission for digitisation not received|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Wolfson Inst for Biomedical Research|
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