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Publication : Cholinergic modulation of striatal nitric oxide-producing interneurons.

First Author  Melendez-Zaidi AE Year  2019
Journal  Eur J Neurosci Volume  50
Issue  11 Pages  3713-3731
PubMed ID  31340071 Mgi Jnum  J:359705
Mgi Id  MGI:7788937 Doi  10.1111/ejn.14528
Citation  Melendez-Zaidi AE, et al. (2019) Cholinergic modulation of striatal nitric oxide-producing interneurons. Eur J Neurosci 50(11):3713-3731
abstractText  Striatal GABAergic interneurons that express nitric oxide synthase-so-called low-threshold spike interneurons (LTSIs)-play several key roles in the striatum. But what drives the activity of these interneurons is less well defined. To fill this gap, a combination of monosynaptic rabies virus mapping (msRVm), electrophysiological and optogenetic approaches were used in transgenic mice in which LTSIs expressed either Cre recombinase or a fluorescent reporter. The rabies virus studies revealed a striking similarity in the afferent connectomes of LTSIs and neighboring cholinergic interneurons, particularly regarding connections arising from the parafascicular nucleus of the thalamus and cingulate cortex. While optogenetic stimulation of cingulate inputs excited both cholinergic interneurons and LTSIs, thalamic stimulation excited cholinergic interneurons, but inhibited LTSIs. This inhibition was dependent on cholinergic interneurons and had two components: a previously described GABAergic element and one that was mediated by M4 muscarinic acetylcholine receptors. In addition to this phasic signal, cholinergic interneurons tonically excited LTSIs through a distinct, M1 muscarinic acetylcholine receptor pathway. This coordinated cholinergic modulation of LTSIs predisposed them to rhythmically burst in response to phasic thalamic activity, potentially reconfiguring striatal circuitry in response to salient environmental stimuli.
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