Nicotinic Acetylcholine Receptors Expressed by Striatal Interneurons Inhibit Striatal Activity and Control Striatal-Dependent Behaviors

0557064 - FGÚ 2023 RIV US eng J - Journal Article
Abbondanza, Alice - Ribeiro Bas, Irina - Modrák, Martin - Čapek, Martin - Minich, Jessica - Tyshkevich, Alexandra - Naser, Shahed - Rangotis, Revan - Houdek, Pavel - Sumová, Alena - Dumas, S. - Bernard, V. - Janíčková, Helena
Nicotinic Acetylcholine Receptors Expressed by Striatal Interneurons Inhibit Striatal Activity and Control Striatal-Dependent Behaviors.
Journal of Neuroscience. Roč. 42, č. 13 (2022), s. 2786-2803. ISSN 0270-6474. E-ISSN 1529-2401
R&D Projects: GA ČR(CZ) GJ19-07983Y; GA MŠMT(CZ) LM2015062; GA MŠMT(CZ) LM2018129; GA MŠMT(CZ) 8J21FR022; GA MŠMT(CZ) LM2018131; GA MŠMT(CZ) EF18_046/0016045
Institutional support: RVO:67985823 ; RVO:61388971
Keywords : acetylcholine * behavior * Fos * interneurons * nAChRs * striatum
OECD category: Neurosciences (including psychophysiology; Neurosciences (including psychophysiology (MBU-M)
Impact factor: 5.3, year: 2022
Method of publishing: Open access
https://doi.org/10.1523/JNEUROSCI.1627-21.2022

Acetylcholine is an important modulator of striatal activity, and it is vital to controlling striatal-dependent behaviors, including motor and cognitive functions. Despite this significance, the mechanisms determining how acetylcholine impacts striatal signaling are still not fully understood. In particular, little is known about the role of nAChRs expressed by striatal interneurons. In the present study, we used FISH to determine which neuronal types express the most prevalent beta2 nicotinic subunit in the mouse striatum. Our data support a common view that nAChR expression is mostly restricted to striatal interneurons. Surprisingly though, cholinergic interneurons were identified as a population with the highest expression of beta2 nicotinic subunit. To investigate the functional significance of beta2containing nAChRs in striatal interneurons, we deleted them by injecting the AAV-Cre vector into the striatum of beta2-flox/flox male mice. The deletion led to alterations in several behavioral domains, namely, to an increased anxiety-like behavior, decrease in sociability ratio, deficit in discrimination learning, and increased amphetamine-induced hyperlocomotion and c-Fos expression in mice with beta2 deletion. Further colocalization analysis showed that the increased c-Fos expression was present in both medium spiny neurons and presumed striatal interneurons. The present study concludes that, despite being relatively rare, beta2-containing nAChRs are primarily expressed in striatal neurons by cholinergic interneurons and play a significant role in behavior.
Permanent Link: http://hdl.handle.net/11104/0331170