title: Serotonergic regulation of excitability of principal cells of the dorsal cochlear nucleus.
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 properties, which may enhance the sensitivity of the DCN to sensory input.
authors: Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239.
authors: Zheng-Quan
authors: ZQ
authors: Tang
authors: Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239 trussell@ohsu.edu.
authors: Laurence O
authors: http://orcid.org/0000-0003-1171-2356
authors: LO
authors: Trussell
mesh_terms: D000818:Animals; D017626:Cochlear Nucleus / Q000166:cytology* / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D012701:Serotonin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D012701:Serotonin
keywords: auditory; serotonin; tinnitus