Effects of acetylcholine in the striatum

Abstract

ACh= : acetylcholine; DA= : dopamine; GABA= : γaminobutyric acid; GPe= : globus pallidus externus; GPi= : globus pallidus internus; ILT= : intralaminar nuclei of the thalamus; LTD= : long-term depression; LTP= : long-term potentiation; MSN= : medium spiny neuron; nAChR= : nicotinic ACh receptor; PD= : Parkinson disease; PIP2= : phosphatidylinositol diphosphate; SNc= : substantia nigra pars compacta; SNr= : substantia nigra pars reticulata The striatum is a nodal structure of the basal ganglia circuits and is one of the brain areas with the highest concentration of markers of cholinergic transmission. Giant aspiny cholinergic interneurons constitute only 1%–3% of the neurons of the striatum but exert a powerful influence on its output, which is mediated by the medium spiny neurons (MSNs). Acetylcholine (ACh), acting via different receptor subtypes, affects the activity of the MSNs both directly and via modulation of glutamate release from corticostriate terminals and of dopamine release from nigrostriatal terminals. Acetylcholine, via its reciprocal interactions with dopamine (DA), has an important role in the differential modulation of striatal output via the so-called direct and indirect pathways of the basal ganglia circuits. Recent evidence indicates that ACh release in the striatum, triggered by thalamic inputs, provides a “stop” signal that interrupts ongoing motor behavior in response to salient stimuli from the environment. Cholinergic mechanisms in the striatum may contribute to the pathophysiology of Parkinson disease (PD) and dystonia, and may have a beneficial role in Tourette syndrome and other stereotypies. The physiology of cholinergic interneurons and the effects of ACh in the striatum recently have been reviewed.1,–,4 ### General organization of the striatum. The striatum comprises anatomic subdivisions that receive inputs from different areas of the frontal lobe and intralaminar nuclei of the thalamus (ILT); it participates in parallel, partially segregated motor, oculomotor, cognitive, and limbic circuits. In addition to these functionally defined territories, the striatum can be subdivided into 2 compartments, the matrix and the striosomes (or patches).5,6 Most neurons (nearly 95%) of the striatum are projection MSNs in both compartments that utilize γ-aminobutyric acid (GABA). MSNs of the matrix include 2 functionally distinct subpopulations that express different proportions of dopaminergic, cholinergic, and other receptors. One MSN population projects to …