Serotonergic regulation of excitability of principal cells of the dorsal cochlear nucleus

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Zheng-Quan Tang, Laurence O Trussell

Abstract

The dorsal cochlear nucleus (DCN) is one of the first stations within the central auditory pathway where the basic computations underlying sound localization are initiated and heightened activity in the DCN may underlie central tinnitus. The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT), is associated with many distinct behavioral or cognitive states, and serotonergic fibers are concentrated in the DCN. However, it remains unclear what is the function of this dense input. Using a combination of in vitro electrophysiology and optogenetics in mouse brain slices, we found that 5-HT directly enhances the excitability of fusiform principal cells via activation of two distinct 5-HT receptor subfamilies, 5-HT2A/2CR (5-HT2A/2C receptor) and 5-HT7R (5-HT7 receptor). This excitatory effect results from an augmentation of hyperpolarization-activated cyclic nucleotide-gated channels (Ih or HCN channels). The serotonergic regulation of excitability is G-protein-dependent and involves cAMP and Src kinase signaling pathways. Moreover, optogenetic activation of serotonergic axon terminals increased excitability of fusiform cells. Our findings reveal that 5-HT exerts a potent influence on fusiform cells by altering their intrinsic prop...Continue Reading

Citations

Jul 1, 2015·Current Opinion in Neurobiology·Peter Keating, Andrew J King
Dec 22, 2015·Hearing Research·Melissa A Papesh, Laura M Hurley
Apr 26, 2016·Nature Neuroscience·Kwang Woo KoNace L Golding
Aug 31, 2016·Proceedings of the National Academy of Sciences of the United States of America·Weipang ChangJianguo G Gu
Sep 22, 2018·International Review of Psychiatry·Frederick S BarrettMendel Kaelen
Oct 4, 2018·Journal of Neurophysiology·Elizabeth Fleming, Court Hull
Apr 26, 2019·American Journal of Audiology·Sarah M Theodoroff, James A Kaltenbach
May 14, 2020·Journal of Neurophysiology·Tyler R SizemoreAndrew M Dacks
Sep 7, 2018·Frontiers in Neuroscience·Patrick KraussHolger Schulze
Nov 27, 2020·Journal of Psychoactive Drugs·Heba Diab, Benjamin Malcolm
Mar 21, 2021·International Journal of Epidemiology·Pei-Xun ZhongLi-Ting Kao
Apr 17, 2021·ACS Pharmacology & Translational Science·Justin C StricklandMatthew W Johnson

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