ABSTRACT
In this chapter we have chosen to review the action of neurotoxins on the Purkinje cell of the cerebellum. There has been considerable interest in this cell type as a site of action for neurotoxicity as it is considered to be a primary target when ataxia is observed in animals or humans upon treatment with pharmacological agents. Hence, Purkinje cells are established as playing a significant role in coordination of motor function. Purkinje cells have also been implicated in processes such as cognitive function (Schreurs et al., 1991, 1992). It is one of the three layers of the cerebellar cortex, situated between the granule cell and the molecular cell layers. The Purkinje cell is one of the larger neuronal cells that is in limited numbers and does not regenerate upon destruction. It has a long axon (Golgi I) that does not extend beyond the cerebellum. Purkinje cells have a spectacular dendritic tree associated with the cell body that branches in the molecular cell layer. Bergmann glial fibers are contained within the molecular cell layer acting to supply nutrients and maintain neuronal functioning. Mossy fibers, which make up the afferent system of the cerebellar cortex, originate from other sites including the spinal cord and brain stem. They branch extensively within the white matter and the granule layer and terminate on the dendrites and axons of the granular cells. The axons of the granular cells form parallel fibers forming synapses directly with dendrites of the Purkinje cells in the molecular layer. The major excitatory input in the dendritic fields is glutamatergic while the inhibitory pathway is GABA-ergic. This synaptic function is critical for maintaining normal activities. Climbing fibers have their origin in the contralateral inferior olive. They branch in the cerebellar white matter, ascend towards the molecular layer, and densely synapse with the dendrites of Purkinje cells. The inferior olive projections form small clusters innervating the Purkinje cells that are aligned in parasagittal rows.
