Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.505541
Title: Generation of the complex spike in cerebellar Purkinje cells
Author: Davie, Jennifer Thorpe
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2008
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Abstract:
Each neuron of the nervous system is a machine specialised to appropriately transform its synaptic inputs into a pattern of spiking output. This is achieved through the combination of specialisations in synaptic properties and location, passive cell geometry and placement of particular active ion channels. The challenge presented to the neuroscientist is to, within each cell type, identify such specialisations in input distribution and resulting active events, and assess their relative importance in the generation of action potential output patterns. The Purkinje cell, in particular its response to climbing fibre (CF) input, is an excellent setting in which to attempt to meet this challenge. The Purkinje cell receives a single, easily isolated CF axon, which makes hundreds of synapses across the cell's highly branched, active dendritic tree, resulting in the generation of prominent dendritic calcium spikes and a distinctive, reproducible burst of fast action potentials (the complex spike) at the soma. In this thesis I have separated out the importance of the size of this input, its location and the active dendritic spikes it triggers in the generation of the complex spike. I have found that, to a large extent, the complex spike pattern is determined by the size of the CF input alone. I have characterised the complex spike (its number of spikes, their timing, height and reliability) at both constant physiological frequency and across a range of paired- pulse depression causing intervals. By alternating between whole cell current and voltage clamp in the same cell, I have recorded both the complex spikes and EPSCs generated at certain paired pulse intervals. In this way I have been able to construct the EPSC - complex spike 'input - output' relationship. This demonstrated that there is a straightforward linear transformation between the EPSC input amplitude and the number and timing of spikes in the complex spike. This applies across cells, explaining a large amount of the inter-cell variability in complex spike pattern. Input location and dendritic spikes have surprisingly little influence over the Purkinje cell complex spike. I found that complex spikes generated by dendritically distributed CF input can be reproduced by using conductance clamp to inject CF-like synaptic conductance at the soma. Both CF input and somatic EPSG injection produced complex spike waveforms that can only be easily explained by a model in which spikelets are initiated at a distant site and variably propagated to the soma. By using simultaneous somatic and dendritic recording I have demonstrated that this distant site initiation site is not in the dendrites. Somatic EPSG injection reproduced complex spikes independently of dendritic spikes, and extra dendritic spikes triggered by CF stimulation were associated with only 0.24 0.09 extra somatic spikelets in the complex spike. Rather, I have found that dendritic spikes, generated reliably by the dendritic location of CF inputs, have a role in regulating the post-complex spike pause. An extra dendritic spike generates a 3.4 0.7 mV deeper AHP and a 52 11 % longer pause before spontaneous spiking resumed. In this way, I have identified specialisations that encode the size, and thus timing, of CF inputs in the complex spike burst, whilst allowing the dendritic excitation of Purkinje cells (which is strongly associated synaptic and intrinsic plasticity) to be simultaneously encoded in the post-complex spike pause. This may reflect the complex spike's proposed dual role in both controlling ongoing movement and correcting for motor errors.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.505541  DOI: Not available
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