Rieubland, SCS; (2013) Functional and anatomical connectivity patterns in the cerebellar cortex. Doctoral thesis , UCL (University College London).

Abstract

The rules governing synaptic connectivity in neural circuits are still poorly understood. In the cerebellar cortex, the general wiring patterns between different cell types are known, but the precise circuit at the level of individual cells is still unclear. In the molecular layer, thought to be the principal site of cerebellar learning, I investigated three fundamental microcircuits and their connectivity: the network of chemically and electrically coupled inhibitory interneurons, their inhibitory connection to Purkinje cells, and their shared parallel fibre input, which together form a feed-forward inhibitory circuit. I used both electrophysiological and anatomical techniques to probe functional and structural connectivity patterns in these circuits. Optimisation was performed to combine electrophysiological recordings and imaging with a focused ion beam scanning electron microscope. The resulting high-resolution three-dimensional imaging reveals the precise connectivity of hundreds of individual parallel fibres. I found that their connectivity is constrained by volume exclusion rules between presynaptic boutons. These spatial constraints are overcome between directly adjacent interneurons and Purkinje cells, receiving input from a common parallel fibre bouton. Using multiple patch-clamp recordings, I found evidence for specific, non-random connectivity amongst molecular layer interneurons. The electrical and chemical networks are both highly clustered and their overlap is non-random. Inhibitory connections between interneurons are preferentially organized in a feed-forward (or transitive) fashion. I show that individual interneurons can both decrease and increase the inhibition received by Purkinje cells, via an indirect connection through electrically coupled interneurons. A highly specific connectivity pattern supports this control of inhibition of Purkinje cells by the coupled network. To summarize, I investigated the rules governing neural connectivity in the molecular layer: from spatial constraints, via formation of specific connectivity motifs, to the implementation of functional roles. This new information will help shape our understanding of the interactions and computations performed in the cerebellar cortex.

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