Sodium salicylate suppresses GABAergic inhibitory activity in neurons of rodent dorsal raphe nucleus

Yan Jin; Bin Luo; Yan-Yan Su; Xin-Xing Wang; Liang Chen; Ming Wang; Wei-Wen Wang; Lin Chen

doi:10.1371/journal.pone.0126956

Sodium salicylate suppresses GABAergic inhibitory activity in neurons of rodent dorsal raphe nucleus

PLoS One. 2015 May 11;10(5):e0126956. doi: 10.1371/journal.pone.0126956. eCollection 2015.

Authors

Yan Jin¹, Bin Luo², Yan-Yan Su³, Xin-Xing Wang⁴, Liang Chen⁴, Ming Wang⁴, Wei-Wen Wang⁵, Lin Chen⁶

Affiliations

¹ CAS Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China.
² Department of Otolaryngology-Head and Neck Surgery, Anhui Provincial Hospital, Hefei, 230001, China.
³ Department of Anatomy, Anhui Medical University, Hefei, 230032, China.
⁴ Auditory Research Laboratory, University of Science and Technology of China, Hefei, 230027, China.
⁵ Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China.
⁶ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Dorsal Raphe Nucleus / cytology*
Dorsal Raphe Nucleus / drug effects*
Female
GABAergic Neurons / drug effects*
GABAergic Neurons / physiology
Inhibitory Postsynaptic Potentials / drug effects
Male
Membrane Potentials / drug effects
Mice
Mice, Transgenic
Patch-Clamp Techniques
Rats
Serotonin / metabolism
Sodium Salicylate / pharmacology*

Substances

Serotonin
Sodium Salicylate

Grants and funding

This work was supported by the National Basic Research Program of China (Grants 2011CB504506 and 2012CB932502), the National Natural Science Foundation of China (Grants 81371503, 31170965, and 81200741) and the Fundamental Research Funds for Central Universities (WK2070000041). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.