Centrality of Striatal Cholinergic Transmission in Basal Ganglia Function

Antonio Pisani,Dario Cuomo,Francesca Puglisi,Giulia Ponterio,Giuseppina Martella,Graziella Madeo,Paola Bonsi,Tommaso Schirinzi

doi:10.3389/fnana.2011.00006

Abstract

Work over the past two decades revealed a previously unexpected role for striatal cholinergic interneurons in the context of basal ganglia function. The recognition that these interneurons are essential in synaptic plasticity and motor learning represents a significant step ahead 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 appears to be the trigger for pathophysiological changes occurring in basal ganglia disorders. Accordingly, there is now compelling evidence showing profound changes in cholinergic markers in these disorders, in particular Parkinson's disease and dystonia. Based on converging experimental and clinical evidence, we provide an overview of the role of striatal cholinergic transmission in physiological and pathological conditions, in the context of the pathogenesis of movement disorders.

Highlights

The large majority of striatal neurons are GABAergic
Based on converging experimental and clinical evidence, we provide an overview of the role of striatal cholinergic transmission in physiological and pathological conditions, in the context of the pathogenesis of movement disorders
GABAergic interneurons may colocalize with the calcium-binding proteins parvalbumin or calretinin, or neuropeptide Y, somatostatin, and NADPH diaphorase (Kawaguchi, 1993; Tepper and Bolam, 2004)

Summary

Introduction

The large majority of striatal neurons are GABAergic. Most of these GABAergic neurons are represented by medium spiny projection neurons (MSNs; Izzo et al, 1987). The predominant effect of dopamine on ChIs is mediated by activation of D2-like D2 receptors (Figure 2), which inhibit striatal ACh efflux (DeBoer et al, 1996), by reducing both autonomous action potential firing and synaptic inputs to ChIs. The former effect is achieved by enhancing the slow inactivation of voltagedependent Na+ channels (Maurice et al, 2004) and by modulating Ih current (Deng et al, 2007).

Results

Conclusion