• U Grüsser-Cornehls and J Bäurle.
• Freie Universität Berlin, Fachbereich Humanmedizin, Universitätsklinikum Benjamin Franklin, Department of Physiology, 14195, Berlin, Germany. gruesser@fub46.zedat.fu-berlin.de
• Prog. Neurobiol. 2001 Apr 1; 63 (5): 489-540.

AbstractNot later than two synapses after their arrival in the cerebellar cortex all excitatory afferent signals are subsequently transformed into inhibitory ones. Guaranteed by the exceedingly ordered and stereotyped synaptic arrangement of its cellular elements, the cerebellar cortex transmits this inhibitory result of cerebellar integration exclusively via Purkinje cells (PCs) in a precise temporal succession directly onto the target neurons of the deep cerebellar and vestibular nuclei. Thus the cerebellar cortex seems to produce a temporal pattern of inhibitory influence on these target neurons that modifies their excitatory action in such a way that an activation of muscle fibers occurs which progressively integrates the intended motion into the actual condition of the motoric inventory. In consequence, disturbances that affect this cerebellar inhibition will cause uncoordinated, decomposed and ataxic movements, commonly referred to as cerebellar ataxia. Electrophysiological investigations using different cerebellar mouse mutants have shown that alterations in the cerebellar inhibitory input in the target nuclei lead to diverse neuronal responses and to different consequences for the behavioural phenotype. A dependence between the reconstitution of inhibition and the behavioural outcome seems to exist. Obviously two different basic mechanisms are responsible for these observations: (1) ineffective inhibition on target neurons by surviving PCs; and (2) enhancement of intranuclear inhibition in the deep cerebellar and vestibular nuclei. Which of the two strategies evolves is dependent upon the composition of the residual cell types in the cerebellum and on the degree of PC input loss in a given area of the target nuclei. Motor behaviour seems to deteriorate under the first of these mechanisms whereas it may benefit from the second. This is substantiated by stereotaxic removal of the remaining PC input, which eliminates the influence of the first mechanism and is able to induce the second strategy. As a consequence, motor performance improves considerably. In this review, results leading to the above conclusions are presented and links forged to human cerebellar diseases.

30 keywords...

hide…