Generation of the complex spike in cerebellar Purkinje cells.
Doctoral thesis, UCL (University College London).
The climbing fibre synaptic input to cerebellar Purkinje cells is remarkable is several respects. It is one of the most powerful connections in the nervous system, being composed of hundreds of synaptic contacts from a single presynaptic axon, which are widely distributed across the Purkinje cell's highly branched main dendrites. Activation of this input triggers prominent calcium spikes in the Purkinje cell's dendrites together with a distinctive burst of rapid spikes in the soma, known as the complex spike. The mechanism of complex spike generation is not yet understood; in particular the contribution of each of these specialisations is unknown. The work presented in my thesis demonstrates that, unexpectedly, the complex spike firing pattern is largely determined by input size alone. The dendritic location of synaptic input and generation of dendritic spikes are not required for complex spike generation. I demonstrate that dendritic spikes are not directly linked to spikelets in the complex spike, and that each dendritic spike triggers only 0.24\pm0.09 extra somatic spikelets. I also describe the voltage sensitivity of the complex spike pattern and how the pattern can be understood as the result of axonal spike initiation followed by backpropagation to the soma. I present data that demonstrates that the dendritic distribution of input is required to reliably trigger dendritic spikes, which are known to play an important role in Purkinje cell intrinsic and synaptic plasticity. Further, I identify a new role for climbing fibre triggered dendritic calcium spikes: regulation of the length of the post-complex spike pause in spontaneous firing. Together, this work demonstrates that the axo-somatic and dendritic compartments of the Purkinje cell act largely separately during the complex spike, the former generating a rapid, reliable burst of action potentials, the latter producing a biochemical calcium signal through dendritic calcium spike generation.
|Title:||Generation of the complex spike in cerebellar Purkinje cells|
|Additional information:||Permission for digitisation not received. Abstract contains LATEX text. Please see thesis for rendered formulae and equations|
|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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