a kind of toggle switch. These findings have been challenged by a study suggesting that such toggling by climbing-fiber inputs occurs predominantly in anaesthetized animals and that Purkinje cells in awake behaving animals, in general, operate almost continuously in the upstate. But this latter study has itself been challenged and Purkinje cell toggling has since been observed in awake cats. A computational model of the Purkinje cell has shown intracellular calcium computations to be responsible for toggling. Findings have suggested that Purkinje cell dendrites release endocannabinoids that can transiently downregulate both excitatory and inhibitory synapses. The intrinsic activity mode of Purkinje cells is set and controlled by the sodium-potassium pump. This suggests that the pump might not be simply a homeostatic, "housekeeping" molecule for ionic gradients. Instead, it could be a computation element in the cerebellum and the brain. Indeed, a mutation in the - pump causes rapid onset dystonia parkinsonism; its symptoms indicate that it is a pathology of cerebellar computation. Furthermore, using the poison ouabain to block - pumps in the cerebellum of a live mouse induces ataxia and dystonia. Numerical modeling of experimental data suggests that, in vivo, the - pump produces long quiescent punctuations (>> 1 s) to Purkinje neuron firing; these may have a computational role. Alcohol inhibits - pumps in the cerebellum and this is likely how it corrupts cerebellar computation and body co-ordination. Clinical significance In humans, Purkinje cells can be harmed by a variety of causes: toxic exposure, e.g. to alcohol or lithium; autoimmune diseases; genetic mutations causing spinocerebellar ataxias, gluten ataxia, Unverricht-Lundborg disease, or autism; and neurodegenerative diseases that are not known to have a genetic basis, such as the cerebellar type of multiple system atrophy or sporadic ataxias. Gluten ataxia is an autoimmune disease triggered by the ingestion of gluten. The death of Purkinje cells as a result of gluten exposure is irreversible. Early diagnosis and treatment with a gluten-free diet can improve ataxia and prevent its progression. Less than 10% of people with gluten ataxia present any gastrointestinal symptom, yet about 40% have intestinal damage. It accounts for 40% of ataxias of unknown origin and 15% of all ataxias. The neurodegenerative disease spinocerebellar ataxia type 1 (SCA1) is caused by an unstable polyglutamine expansion within the Ataxin 1 protein. This defect in Ataxin 1 protein causes impairment of mitochondria in Purkinje cells, leading to premature degeneration of the Purkinje