Inhibiting cholinergic signalling in the cerebellar interpositus nucleus impairs motor behaviour.

Abstract

The role of neuromodulators in the cerebellum is not well understood. In particular, the behavioural significance of the cholinergic system in the cerebellum is unknown. To investigate the importance of cerebellar cholinergic signalling in behaviour, we infused acetylcholine receptor antagonists, scopolamine and mecamylamine, bilaterally into the rat cerebellum (centred on interpositus nucleus) and observed the motor effects through a battery of behavioural tests. These tests included unrewarded behaviour during open field exploration and a horizontal ladder walking task and reward-based beam walking and pellet reaching tasks. Infusion of a mix of the antagonists did not impair motor learning in the horizontal ladder walking or the reaching task but reduced spontaneous movement during open field exploration, impaired coordination during beam walking and ladder walking, led to fewer reaches in the pellet reaching task, slowed goal-directed reaching behaviour and reduced reward pellet consumption in a free access to food task. Infusion of the muscarinic antagonist scopolamine on its own resulted in deficits in motor performance and a reduction in the number of reward pellets consumed in the free access to food task. By contrast, infusion of the nicotinic antagonist mecamylamine on its own had no significant effect on any task, except beam walking traversal time, which was reduced. Together, these data suggest that acetylcholine in the cerebellar interpositus nucleus is important for the execution and coordination of voluntary movements mainly via muscarinic receptor signalling, especially in relation to reward-related behaviour.