A regulatory role of the medial septum in the chloroquine-induced acute itch through local GABAergic system and GABAergic pathway to the anterior cingulate cortex

• Published in: Biochemical and biophysical research communications 2024-08, Vol.721, p.150145, Article 150145
• Main Authors: Zhu, Jianyu, Yang, Yayue, Du, Lixia, Yang, Wei, Yang, Yachen, Yi, Ting, Maoying, Qiliang, Chu, Yuxia, Wang, Yanqing, Mi, Wenli
• Format: Article
• Language: English
• Subjects: Acute itch; Anterior cingulate cortex; GABA; GABAergic pathway; Medial septum
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.150145

Itch, a common somatic sensation, serves as a crucial protective system. Recent studies have unraveled the neural mechanisms of itch at peripheral, spinal cord as well as cerebral levels. However, a comprehensive understanding of the central mechanism governing itch transmission and regulation remains elusive. Here, we report the role of the medial septum (MS), an integral component of the basal forebrain, in modulating the acute itch processing. The increases in c-Fos+ neurons and calcium signals within the MS during acute itch processing were observed. Pharmacogenetic activation manipulation of global MS neurons suppressed the scratching behaviors induced by chloroquine or compound 48/80. Microinjection of GABA into the MS or pharmacogenetic inhibition of non-GABAergic neurons markedly suppressed chloroquine-induced scratching behaviors. Pharmacogenetic activation of the MS-ACC GABAergic pathway attenuated chloroquine-induced acute itch. Hence, our findings reveal that MS has a regulatory role in the chloroquine-induced acute itch through local increased GABA to inhibit non-GABAergic neurons and the activation of MS-ACC GABAergic pathway. •MS neurons are activated during pruritogens-induced acute itch.•Pharmacogenetic activation of MS neurons suppressed pruritogens-induced scratching behaviors.•Pharmacogenetic inhibition of MS non-GABAergic neurons reduced chloroquine-induced scratching behavior.•Pharmacogenetic activation of MS-ACC GABAergic pathway suppressed chloroquine-induced acute itch behavior.