Spontaneous activity and sensory integration in cerebellar neurons in vivo.
Doctoral thesis, UCL (University College London).
To understand the information flow in neural circuits, it is essential to determine how neurons translate synaptic input into spike output. In the cerebellum, Golgi cells are the only interneurons that inhibit granule cells in the input layer, where mossy fibre (MF) signals converge onto both cell types. Golgi cells also receive inputs from parallel fibres (PFs, granule cell axons) that form synaptic contacts with the molecular layer interneurons and Purkinje cells. This synaptic organisation suggests the Golgi cells may be an important regulatory element in the cerebellar circuit. In this thesis, I used targeted patch-clamp recordings guided by 2-photon microscopy to examine the synaptic input and spike output patterns of Golgi cells in anaesthetised transgenic mice. I found that Golgi cells received bursty and occasionally rhythmic excitatory inputs and sparse inhibitory inputs in vivo. My results also revealed that Golgi cells exhibit low spontaneous firing rates, and their spiking activity can display 1 Hz rhythmicity and synchrony with millisecond precision. Remarkably, Golgi cells usually generated only a single spike time-locked to the stimulus by integrating multiple synaptic inputs during sensory stimulation. These results suggest that Golgi cells encode temporal information in their spikes, and will therefore transfer this message throughout the cerebellar network by controlling granule cell (PF) activity. Purkinje cells, the sole output neurons of the cerebellar cortex, often display large, single "all-or-none" synaptic responses from the strong excitation by climbing-fibre (CF) inputs in vitro. However, the transmission at the CF-Purkinje cell synapse in the intact brain remains poorly understood. Using whole-cell voltage clamp recordings from Purkinje cells in anaesthetised rats, I revealed that the spontaneous CF excitatory postsynaptic currents (CF-EPSCs) can be bursty, indicating that high-frequency olivary axonal signals are transmitted to the cerebellum in vivo.
|Title:||Spontaneous activity and sensory integration in cerebellar neurons in vivo|
|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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