Cholinergic Interneuron and Parkinsonism

Recent advances in our knowledge of striatal function revealed a previously unexpected role for striatal cholinergic interneurons. The recognition that interneurons are essential in synaptic plasticity and motor learning represents a significant progress in deciphering how the striatum processes cortical inputs, and why pathological circumstances cause motor dysfunction. Loss of the reciprocal modulation between dopaminergic inputs and the intrinsic cholinergic innervation within the striatum represents a suitable explanation for the efficacy of anticholinergic drugs both in Parkinson’s disease and in dystonia. These advances provide exciting indications to the underlying circuit alterations. In this chapter, we discuss the experimental and clinical evidence in attempt to clarify how alterations in striatal cholinergic signalling may contribute to motor dysfunction and ultimately to identify novel therapeutic strategies to fine-tune cholinergic signalling in basal ganglia disorders.