Probing striatal microcircuitry to understand the functional role of cholinergic interneurons.
Probing striatal microcircuitry to understand the functional role of cholinergic interneurons.
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DOI：
10.1002/mds.26340
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Nelson AB
中科院分区：
文献类型：
--
作者：
Girasole AE;Nelson AB
The function of acetylcholine in the striatum has perplexed basal ganglia physiologists and clinicians for decades. The effects of cholinergic and anticholinergic agents in patients with movement disorders, as well as in animal models of basal ganglia-dependent behaviors, suggest a critical role for acetylcholine in the normal function of the basal ganglia. The highest density of acetylcholine in the basal ganglia occurs in the input nucleus, the striatum, suggesting it might be the site of action. Striatal acetylcholine predominantly derives from local cholinergic interneurons, which form a dense network of cholinergic fibers throughout the striatum. 1 These cholinergic interneurons represent a small percentage of all striatal neurons, but fire tonically and contribute to some of the brain's highest levels of acetylcholine. 1-4 Another source of striatal acetylcholine is extrinsic cholinergic input to the striatum, deriving from brainstem structures. Acetylcholine regulates the function of the striatal microcircuit and striatal output, via a combination of nicotinic and muscarinic acetylcholine receptors. Acetylcholine also regulates striatal dopamine release, which may modulate symptoms in disorders such as Parkinson's Disease, dystonia, and Tourette Syndrome. Fluctuations in levels of both transmitters are believed to contribute to pathological circuit activity and drive symptoms, and are a prominent target of current therapeutic agents. In both normal and disease states, dopamine and acetylcholine concomitantly influence striatal projection neurons to affect a broad number of basal ganglia-mediated behaviors, including control of movement, motivation, and decisionmaking.The goal of this Perspective is to discuss how recent research has modified our view of the function of striatal cholinergic interneurons. First, we will provide some background on the striatal circuit components and theories regarding acetylcholine's site of action, discussing recent studies that have clarified or altered these ideas. Next, we will discuss the hypothesized role of acetylcholine in several prominent movement disorders. Finally, we will outline some outstanding questions within the field, and how recent technological advances might allow further exploration of the mechanisms by which acetylcholine
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