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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<jats:italic>in vitro<\/jats:italic>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-HT<jats:sub>2A\/2C<\/jats:sub>R (5-HT<jats:sub>2A\/2C<\/jats:sub>receptor) and 5-HT<jats:sub>7<\/jats:sub>R (5-HT<jats:sub>7<\/jats:sub>receptor). This excitatory effect results from an augmentation of hyperpolarization-activated cyclic nucleotide-gated channels (<jats:italic>I<\/jats:italic><jats:sub>h<\/jats:sub>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.<\/jats:p>","DOI":"10.1523\/jneurosci.4825-14.2015","type":"journal-article","created":{"date-parts":[[2015,3,18]],"date-time":"2015-03-18T16:50:22Z","timestamp":1426697422000},"page":"4540-4551","source":"Crossref","is-referenced-by-count":76,"title":["Serotonergic Regulation of Excitability of Principal Cells of the Dorsal Cochlear Nucleus"],"prefix":"10.1523","volume":"35","author":[{"given":"Zheng-Quan","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1171-2356","authenticated-orcid":false,"given":"Laurence O.","family":"Trussell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2015,3,18]]},"reference":[{"key":"2023041304160709000_35.11.4540.1","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/S0022-3565(24)37821-8","article-title":"Functional characterization of the recombinant human 5-hydroxytryptamine7(a) receptor isoform coupled to adenylate cyclase stimulation","volume":"287","author":"Adham","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"2023041304160709000_35.11.4540.2","doi-asserted-by":"publisher","DOI":"10.3109\/00206099809072971"},{"key":"2023041304160709000_35.11.4540.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(00)00026-5"},{"key":"2023041304160709000_35.11.4540.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5555-12.2013"},{"key":"2023041304160709000_35.11.4540.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.06.008"},{"key":"2023041304160709000_35.11.4540.6","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1998.6901"},{"key":"2023041304160709000_35.11.4540.7","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(91)90128-B"},{"key":"2023041304160709000_35.11.4540.8","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000211740.47960.8b"},{"key":"2023041304160709000_35.11.4540.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.03.044"},{"key":"2023041304160709000_35.11.4540.10","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003853.pub3"},{"key":"2023041304160709000_35.11.4540.11","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1152\/jn.1993.70.4.1420","article-title":"Hyperpolarization-activated cation current (Ih) in neurons of the medial nucleus of the trapezoid body: voltage-clamp analysis and enhancement by norepinephrine and cAMP suggest a modulatory mechanism in the auditory brain stem","volume":"70","author":"Banks","year":"1993","journal-title":"J Neurophysiol"},{"key":"2023041304160709000_35.11.4540.12","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5113-03.2004"},{"key":"2023041304160709000_35.11.4540.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.09.026"},{"key":"2023041304160709000_35.11.4540.14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.277806"},{"key":"2023041304160709000_35.11.4540.15","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(89)90041-X"},{"key":"2023041304160709000_35.11.4540.16","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301294"},{"key":"2023041304160709000_35.11.4540.17","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005123"},{"key":"2023041304160709000_35.11.4540.18","doi-asserted-by":"publisher","DOI":"10.1038\/ng0897-387"},{"key":"2023041304160709000_35.11.4540.19","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1523\/JNEUROSCI.22-06-02383.2002","article-title":"Elevated fusiform cell activity in the dorsal cochlear nucleus of chinchillas with psychophysical evidence of tinnitus","volume":"22","author":"Brozoski","year":"2002","journal-title":"J Neurosci"},{"key":"2023041304160709000_35.11.4540.20","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-011-0290-3"},{"key":"2023041304160709000_35.11.4540.21","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(88)90342-6"},{"key":"2023041304160709000_35.11.4540.22","doi-asserted-by":"crossref","first-page":"4854","DOI":"10.1523\/JNEUROSCI.18-13-04854.1998","article-title":"Quantitative evaluation of 5-hydroxytryptamine (serotonin) neuronal release and uptake: an investigation of extrasynaptic transmission","volume":"18","author":"Bunin","year":"1998","journal-title":"J Neurosci"},{"key":"2023041304160709000_35.11.4540.23","doi-asserted-by":"publisher","DOI":"10.1002\/lary.21670"},{"key":"2023041304160709000_35.11.4540.24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.0507p.x"},{"key":"2023041304160709000_35.11.4540.25","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S0022-3565(24)29551-3","article-title":"A 5-HT(7) receptor-mediated depolarization in the anterodorsal thalamus: I. 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