Abstract
How the cerebellum carries out its functions is not clear, even for its established roles in motor control. In particular, little is known about how the cerebellar nuclei (CN) integrate their synaptic and neuromodulatory inputs to generate cerebellar output. CN neurons receive inhibitory inputs from Purkinje cells, excitatory inputs from mossy fibre and climbing fibre collaterals, as well as a variety of neuromodulatory inputs, including cholinergic inputs. In this study we tested how activation of acetylcholine receptors modulated firing rate, intrinsic properties and synaptic transmission in the CN. Using in vitro whole-cell patch clamp recordings from neurons in the interpositus nucleus, the acetylcholine receptor agonist carbachol was shown to induce a short-term increase in firing rate, increase holding current and decrease input resistance of interpositus CN neurons. Carbachol also induced long-term depression of evoked inhibitory postsynaptic currents and a short-term depression of evoked excitatory postsynaptic currents. All effects were shown to be dependent upon muscarinic acetylcholine receptor activation. Overall, the present study has identified muscarinic receptor activation as a modulator of CN activity.
Highlights
The cerebellum, a structure containing approximately 80% of neurons in the human brain [1], has well-established roles in motor functions including coordination, balance, postural control, the accurate execution of fine movements, and in association with such roles it is central to motor learning [2, 3]
To investigate the receptor subtypes involved in the carbachol-induced increase in firing rate, carbachol was co-applied with the broad-spectrum muscarinic receptor antagonist scopolamine (10 μM)
To test if there was any tonic activation of muscarinic receptors in the slice preparation, scopolamine was applied in the absence of carbachol
Summary
The cerebellum, a structure containing approximately 80% of neurons in the human brain [1], has well-established roles in motor functions including coordination, balance, postural control, the accurate execution of fine movements, and in association with such roles it is central to motor learning [2, 3]. The cerebellum has been linked to a number of nonmotor functions, including cognitive planning [4], spatial representation [5], fear responses [6], sensory processing [7], language [8] and attention [9]. This wide range of functions is likely due to connections—either direct or indirect— with a wealth of brain regions including, but not limited to, the motor cortex [10], basal ganglia [11], prefrontal cortex [12,13,14] and hippocampus [15, 16]. Despite early evidence for roles of the cholinergic system in modulating CN activity [e.g. 17] and extensive studies on this system in other brain regions, little is known about the roles of acetylcholine in the cerebellum
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