Cholinergic modulation of striatal microcircuits

Abstract

The purpose of this review is to bridge the gap between earlier literature on striatal cholinergic interneurons and mechanisms of microcircuit interaction demonstrated with the use of newly available tools. It is well known that the main source of the high level of acetylcholine in the striatum, compared to other brain regions, is the cholinergic interneurons. These interneurons provide an extensive local innervation that suggests they may be a key modulator of striatal microcircuits. Supporting this idea requires the consideration of functional properties of these interneurons, their influence on medium spiny neurons, other interneurons, and interactions with other synaptic regulators. Here, we underline the effects of intrastriatal and extrastriatal afferents onto cholinergic interneurons and discuss the activation of pre- and postsynaptic muscarinic and nicotinic receptors that participate in the modulation of intrastriatal neuronal interactions. We further address recent findings about corelease of other transmitters in cholinergic interneurons and actions of these interneurons in striosome and matrix compartments. In addition, we summarize recent evidence on acetylcholine-mediated striatal synaptic plasticity and propose roles for cholinergic interneurons in normal striatal physiology. A short examination of their role in neurological disorders such as Parkinson's, Huntington's, and Tourette's pathologies and dystonia is also included.

Compartmental function and modulation of the striatum

“…Cholinergic interneurons are the main source of ACh in the striatum. While CIN cell bodies tend to reside in the matrix and peristriosomal boundaries, and their neuropil is more extensive in the matrix, CINs are indeed present in both compartments and their processes do cross striosome-matrix boundaries (Abudukeyoumu et al, 2018;Bernacer, Prensa, & Gimenez-Amaya, 2007;Brimblecombe & Cragg, 2017;Crittenden, Lacey, Lee, Bowden, & Graybiel, 2014;Crittenden et al, 2017;Goldberg & Reynolds, 2011;Graybiel, Baughman, & Eckenstein, 1986;Inoue, Suzuki, Nishimura, & Miura, 2016;Jakab & Goldman-Rakic, 1996). Cholinergic signaling modulates myriad aspects of striatal circuit function (including cellular excitability, synaptic transmission and plasticity, dopamine release, and circuit responses to salient cues), which are reviewed elsewhere (Abudukeyoumu et al, 2018;Gerfen & Surmeier, 2011;Goldberg & Reynolds, 2011;Plotkin & Goldberg, 2018), but we are only beginning to understand how this modulation occurs within the context of the striatum's compartmental organization.…”

“…Fundamental to understanding compartmental differences in cholinergic signaling is the recent observation that CIN activity itself may be differentially modulated in striosomes versus matrix. CINs excite several classes of striatal GABAergic interneurons, via postsynaptic nicotinic acetylcholine receptors (nAChRs), which in turn send GABAergic projections back to CINs, forming an inhibitory feedback loop (Abudukeyoumu et al, 2018;Assous & Tepper, 2019). This feedback loop is considerably stronger in the matrix (Inoue et al, 2016).…”

“…How is compartment-specific activity of SPNs achieved in a behaviorally relevant way? This likely involves an interplay between (a) selective activation of afferents; (b) modulation of neuronal activity and synaptic transmission by neuromodulators such as dopamine (DA), acetylcholine (ACh), and opioid peptides; and (c) interneuron-mediated intra-and inter-compartmental signaling (Abudukeyoumu, Hernandez-Flores, Garcia-Munoz, & Arbuthnott, 2018;Brimblecombe & Cragg, 2017;Brimblecombe et al, 2018;Crittenden & Graybiel, 2011;Friedman et al, 2015). Despite evidence supporting the importance of compartment-specific striatal output in shaping behavior (Amemori et al, 2011;Bloem et al, 2017;Canales, 2005;Friedman et al, 2015), progress toward understanding the underlying mechanisms had largely been impeded by technical limitations.…”

Papers arising from the 12th International Basal Ganglia Society Meeting. March 26th–30th 2017, Mérida, Yucatán, México

“…Two review articles dealing with the roles of interneurons (Abudukeyoumu et al ., ; Assous & Tepper, ) are within the category of basal ganglia circuitry. Assous & Tepper () emphasise the impact of interneurons and their circuitry on the effects of extrinsic inputs on striatal activity, while Abudukeyoumu et al .…”

“…Assous & Tepper () emphasise the impact of interneurons and their circuitry on the effects of extrinsic inputs on striatal activity, while Abudukeyoumu et al . () summarise the role of acetylcholine‐mediated striatal synaptic plasticity and propose roles for cholinergic interneurons in normal striatal function. In an original article Fuccillo et al .…”