title: Sodium salicylate suppresses GABAergic inhibitory activity in neurons of rodent dorsal raphe nucleus.
abstract: Sodium salicylate (NaSal), a tinnitus inducing agent, can activate serotonergic (5-HTergic) neurons in the dorsal raphe nucleus (DRN) and can increase serotonin (5-HT) level in the inferior colliculus and the auditory cortex in rodents. To explore the underlying neural mechanisms, we first examined effects of NaSal on neuronal intrinsic properties and the inhibitory synaptic transmissions in DRN slices of rats by using whole-cell patch-clamp technique. We found that NaSal hyperpolarized the resting membrane potential, decreased the input resistance, and suppressed spontaneous and current-evoked firing in GABAergic neurons, but not in 5-HTergic neurons. In addition, NaSal reduced GABAergic spontaneous and miniature inhibitory postsynaptic currents in 5-HTergic neurons. We next examined whether the observed depression of GABAergic activity would cause an increase in the excitability of 5-HTergic neurons using optogenetic technique in DRN slices of the transgenic mouse with channelrhodopsin-2 expressed in GABAergic neurons. When the GABAergic inhibition was enhanced by optical stimulation to GABAergic neurons in mouse DRN, NaSal significantly depolarized the resting membrane potential, increased the input resistance and increased current-evoked firing of 5-HTergic neurons. However, NaSal would fail to increase the excitability of 5-HTergic neurons when the GABAergic synaptic transmission was blocked by picrotoxin, a GABA receptor antagonist. Our results indicate that NaSal suppresses the GABAergic activities to raise the excitability of local 5-HTergic neural circuits in the DRN, which may contribute to the elevated 5-HT level by NaSal in the brain.
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Anhui Provincial Hospital, Hefei, 230001, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
authors.affiliation: Department of Anatomy, Anhui Medical University, Hefei, 230032, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Su
authors.affiliation: Auditory Research Laboratory, University of Science and Technology of China, Hefei, 230027, China.
authors.forename: Xin-Xing
authors.initials: XX
authors.lastname: Wang
authors.affiliation: Auditory Research Laboratory, University of Science and Technology of China, Hefei, 230027, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Auditory Research Laboratory, University of Science and Technology of China, Hefei, 230027, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China; Auditory Research Laboratory, University of Science and Technology of China, Hefei, 230027, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D065847:Dorsal Raphe Nucleus / Q000166:cytology* / Q000187:drug effects*; D005260:Female; D059330:GABAergic Neurons / Q000187:drug effects* / Q000502:physiology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D012980:Sodium Salicylate / Q000494:pharmacology*
chemical_list: D012701:Serotonin; D012980:Sodium Salicylate