Changes in GABA and glutamate receptors on auditory cortical excitatory neurons in a rat model of salicylate-induced tinnitus

Cong Wu; Xu Wu; Bin Yi; Mengchen Cui; Xueling Wang; Qixuan Wang; Hao Wu; Zhiwu Huang

Changes in GABA and glutamate receptors on auditory cortical excitatory neurons in a rat model of salicylate-induced tinnitus

Am J Transl Res. 2018 Dec 15;10(12):3941-3955. eCollection 2018.

Authors

Cong Wu^{1

2

3}, Xu Wu^{1

2

3}, Bin Yi^{1

2

3}, Mengchen Cui^{2

3}, Xueling Wang^{1

2

3}, Qixuan Wang^{1

2

3}, Hao Wu^{1

2

3}, Zhiwu Huang^{1

2

3}

Affiliations

¹ Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
² Laboratory of Auditory Neuroscience, Ear Institute, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
³ Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases Shanghai, China.

PMID: 30662641
PMCID: PMC6325520

Abstract

Tinnitus is associated with neural hyperactivity, which is regulated by neuronal plasticity in the auditory central system, especially the auditory cortex (AC). Excitatory neurons constitute approximately 70-85% of the total populations of neuronal cells. However, few reports have focused on the AMPA receptor (AMPAR) and the GABA_A receptor (GABA_AR) on the excitatory neuron in animal model of tinnitus. In this study, we gave rats a single or long-term of salicylate administrations. The tinnitus-like behavior was assessed by combination of the gap prepulse inhibition of acoustic startle (GPIAS) and the pre-pulse inhibition (PPI) tests. Using immunofluorescent staining, we examined whether the AMPAR and the GABA_AR on the calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) -labeled excitatory neurons in the auditory cortex underwent changes following salicylate treatment. The rats with 14 days of salicylate administration showed evidence of experiencing tinnitus, while the rats receiving a single dose of salicylate manifested no tinnitus-like behavior. Furthermore, the AMPAR and GABA_AR responded in a homeostatic manner after a single dose of salicylate while those showing in a Hebbian way after long-term salicylate administration. Thus, the different patterns of plasticity change in cortical excitatory neurons might affect the generating of salicylate-induced tinnitus.

Keywords: GABA receptor; Tinnitus; auditory cortical excitatory neuron; glutamate receptor; salicylate.