Ultrastructural localisation and functional implications of Corticotropin releasing factor, Urocortin and their receptors in cerebellar neuronal development

The cerebellar circuitry plays a central role in motor coordination and motor learning. What’s more, the development of motor coordination is dependent upon the development of the cerebellum and its circuitry. Thus, an understanding of the factors influencing cerebellar development is integral to elucidating how normal motor development ensues and allows for directed interventions in cases of pathologies. A plethora of neuropeptides are expressed within the cerebellum and in pre-cerebellar centres, which supply the cerebellar afferents. In this thesis, we investigate the role of corticotropin releasing factor (CRF) and urocortin in the developing rat cerebellum in an attempt to idendtify causal relations between their spatial and temporal expression, well-defined stages of cerebellar development and motor development. Both CRF and urocortin initially are distributed diffusely throughout the cerebellum and at later stages expression predominates in the posterior cerebellum, or the vestibulo-cerebellum. An important difference at later stages is that whilst CRF is exclusively expressed in the cerebellar afferents, urocortin is localised in the afferents as well as Purkinje neurons, the sole output of the cerebellar cortex. The receptors of CRF and urocortin are expressed in climbing fibres and their contacts, the Purkinje cells, suggesting that the receptors modulate the release of CRF and urocortin from climbing fibres as well as the effects of these peptides on Purkinje cells once they are released. Finally, using organotypic slice cultures, we have shown that CRF and urocortin have direct and differential trophic actions on Purkinje cells, inducing the outgrowth and differentiation of Purkinje cell dendrites