Kanichay, R.T.; (2008) Feed-forward excitation of interneurons in the cerebellar granule cell layer. Doctoral thesis , University of London.

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Abstract

The cerebellum is involved in maintenance of posture and balance and coordination of voluntary movements. It has previously been shown that the inhibition of granule cells by Golgi cells, in the input layer of the cerebellar cortex, is important for normal cerebellar function. However, little is known about what determines the firing of spontaneously active Golgi cells and how intrinsic activity interacts with sensory input. In particular, the excitation of the interneuron by mossy fibres, which may mediate feed-forward inhibition of granule cells, has not been characterized. I have used immuno-histochemistry, patch-clamp recordings and imaging in acute cerebellar slices of rats to study feed-forward mossy fibre input onto Golgi cells and its downstream effects. I confirm that mossy fibres, Golgi cells and granule cells form a functional feed-forward inhibitory circuit. Anatomical analysis of the circuitry suggests that only spatially correlated inputs result in feed-forward inhibition. Activation of the pathway required synchronous activity in 4 out of the approximately 10 mossy fibres contacting a Golgi cell. These inputs can reset the timing of spontaneous Golgi cell firing with remarkably high temporal precision. I found that an interaction between fast EPSC kinetics, electronic compactness and pacemaker conductances allowed precise temporal signaling while integrating only 6 quanta across the dendritic tree of a Golgi cell. Golgi cell mean firing rate was only weakly modulated by mossy fibre input due to dominant pacemaker conductances. These results suggest that the properties of the feed-forward mossy fibre - Golgi cell - granule cell pathway are tuned to detect and signal coincident synaptic activity with high temporal precision. This provides a likely synaptic basis for precisely timed Golgi cell responses observed in vivo, which may signal the onset of sensory stimulation producing spatiotemporally correlated mossy fibre activity. These findings are discussed in the context of current models of granule cell layer processing.

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