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Title: Sensory integration in single neurons of the cerebellar cortex
Author: Chadderton, Paul Thomas
ISNI:       0000 0001 3525 7963
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2005
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To understand the computations performed by the neurons within cortical structures it is essential to determine the relationship between sensory-evoked synaptic input and the resulting pattern of output spikes. In the cerebellum, granule cells constitute the input layer, translating mossy fibre signals into parallel fibre input to Purkinje cells. Until now their small size and dense packing have precluded recordings from individual granule cells in vivo. Here I use whole-cell patch-clamp recordings to show the relationship between mossy fibre synaptic currents evoked by somatosensory stimulation and the resulting granule cell output patterns. Granule cells exhibited low ongoing firing rates, due in part to dampening of excitability by a tonic inhibitory conductance mediated by gamma-aminobutyric acid type A (GABAA) receptors. Sensory stimulation produced bursts of mossy fibre excitatory postsynaptic currents that summate and trigger bursts of spikes. Remarkably, burst responses were evoked by only a few quantal excitatory postsynaptic currents. Recordings from putative mossy fibre terminals suggest that sensory-evoked granule cell spiking may result from high frequency activation of single mossy fibres. These results reveal that the input layer of the cerebellum balances exquisite sensitivity with a high signal-to-noise ratio. Granule cell bursts are optimally suited to trigger glutamate receptor activation and plasticity at downstream synapses, providing a link between input representation and memory storage in the cerebellum. Purkinje cells integrate inputs from other neurons in the cerebellar cortex to provide the sole output of the cerebellar cortex. Using whole-cell and cell-attached recordings, I describe a profound and robust bistability of spike output and membrane potential in these cells. Membrane potential toggles between a hyperpolarised down state and an active up state, in a complex spike-dependent manner. Sensory-evoked complex spikes reliably induced state transitions in both directions, indicating that bistability may be relevant for sensory processing in the cerebellum.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available