Junxiu Liu

Salicylate blocks L-type calcium channels in rat inferior colliculus neurons

To investigate the effects of the tinnitus inducer sodium salicylate on L-type voltage-gated calcium channels, we studied freshly dissociated inferior colliculus neurons of rats by the whole-cell voltage clamp method. Salicylates blocking of L-type calcium channels was concentration dependent, and the IC(50) value of salicylate was estimated to be 1.99 mM. An amount of 1 mM salicylate significantly shifted the steady-state inactivation curve of L-type calcium channels about 9 mV in the hyperpolarizing direction and significantly delayed calcium channel recovery. Our results suggest that salicylates blocking of L-type calcium channels may contribute to salicylate-induced tinnitus by decreasing GABA release in the inferior colliculus.

Inhibition of voltage-gated channel currents in rat auditory cortex neurons by salicylate

Salicylate is a medicine for anti-inflammation with a side effect of tinnitus. To understand the mechanisms of tinnitus induced by salicylate, we studied the effects of salicylate on voltage-gated ion channels and action potential firing rates in freshly dissociated rat pyramidal neurons in auditory cortex (AC) using the whole-cell patch technique. We found that salicylate reduced the voltage-gated sodium current (I(Na)), the delayed rectifier potassium current (I(K(DR))) and the L-type voltage-gated calcium current (I(Ca,L)) in concentration-dependent manner. An amount of 1mM salicylate shifted the steady-state inactivation curve of I(Na) negatively by about 5mV, shifted the steady-state activation and inactivation curve of I(K(DR)) negatively by approximately 14mV and 17mV, respectively, and shifted the steady-state activation curve of I(Ca,L) negatively by about 10mV. 1mM salicylate significantly increased the action potential firing rates, ultimately. From the results, we speculated that through affecting the voltage-gated ion channels in AC, an important position in auditory system, salicylate increased the firing rate of neurons and enhanced neuronal excitability on the one hand, increased the excitatory transmitters release and reduced the inhibitory transmitter release on the other hand, thus finally induced tinnitus.

Diazepam reduces excitability of amygdala and further influences auditory cortex following sodium salicylate treatment in rats.

Abstract Conclusion: Diazepam can reduce the excitability of lateral amygdala and eventually suppress the excitability of the auditory cortex in rats following salicylate treatment, indicating the regulating effect of lateral amygdala to the auditory cortex in the tinnitus procedure. Objective: To study the spontaneous firing rates (SFR) of the auditory cortex and lateral amygdala regulated by diazepam in the tinnitus rat model induced by sodium salicylate. Materials and methods: This study first created a tinnitus rat modal induced by sodium salicylate, and recorded SFR of both auditory cortex and lateral amygdala. Then diazepam was intraperitoneally injected and the SFR changes of lateral amygdala recorded. Finally, diazepam was microinjected on lateral amygdala and the SFR changes of the auditory cortex recorded. Results: Both SFRs of the auditory cortex and lateral amygdala increased after salicylate treatment. SFR of lateral amygdala decreased after intraperitoneal injection of diazepam. Microinjecting diazepam to lateral amygdala decreased SFR of the auditory cortex ipsilaterally and contralaterally.

Paraflocculus plays a role in salicylate-induced tinnitus

ABSTRACT Tinnitus impairs quality of life of about 1–2% of the whole population. In most severe situation, tinnitus may cause social isolation, depression and suicide. Drug treatments for tinnitus are generally ineffective, and the mechanisms of tinnitus are still undetermined. Accumulating evidence suggests that tinnitus is related to changes of widespread brain networks. Recent studies propose that paraflocculus (PFL), which is indirectly connected to various cortical regions, may be a gating zone of tinnitus. So we examined the electrophysiological changes and neurotransmitter alterations of the PFL in a rat model of sodium salicylate (SS)‐induced tinnitus. We found that spontaneous firing rate (SFR) of the putative excitatory interneurons of the PFL was significantly increased. The level of glutamic acid, which is the main excitatory neurotransmitter in the nervous system, was also dramatically increased in the PFL after SS treatment. These results confirmed the hyperactivity of PFL in the rats with SS‐treatment, which might be due to the increased glutamic acid. Then we examined the SFR of the auditory cortex (AC), the center for auditory perception, before and after electrical stimulation of the PFL. 71.4% (105/147) of the recorded neurons showed a response to the stimulation of the PFL. The result demonstrated that stimulation of the PFL could modulate the activity of the AC. Our study suggests a role of PFL in SS‐induced tinnitus and AC as a potential target of PFL in the process of tinnitus. HIGHLIGHTSSalicylate injection increased spontaneous firing rates in paraflocculus.Electric stimulation changed neural firing in auditory cortex.Extracellular glutamic acid was significantly increased by salicylate.

Effect of Neuronal Excitability in Hippocampal CA1 Area on Auditory Pathway in a Rat Model of Tinnitus

Background: Tinnitus is a common disorder that causes significant morbidity; however, the neurophysiological mechanism is not yet fully understood. A relationship between tinnitus and limbic system has been reported. As a significant component of the limbic system, the hippocampus plays an important role in various pathological processes, such as emotional disturbance, decreased learning ability, and deterioration of memory. This study was aimed to explore the role of the hippocampus in the generation of tinnitus by electrophysiological technology. Methods: A tinnitus model was established in rats through intraperitoneal injection of salicylate (SA). Subsequently, the spontaneous firing rate (SFR) of neurons in the hippocampal CA1 area was recorded with in vivo multichannel recording technology to assess changes in excitability induced by SA. To investigate the effect of excitability changes of hippocampus on the auditory pathway, the hippocampus was electrically stimulated and neural excitability in the auditory cortex (AC) was monitored. Results: Totally 65 neurons in the hippocampal CA1 area were recorded, 45 from the SA group (n = 5), and 20 from the saline group (n = 5). Two hours after treatment, mean SFR of neurons in the hippocampal CA1 area had significantly increased from 3.06 ± 0.36 Hz to 9.18 ± 1.30 Hz in the SA group (t = −4.521, P < 0.05), while no significant difference was observed in the saline group (2.66 ± 0.36 Hz vs. 2.16 ± 0.36 Hz, t = 0.902, P > 0.05). In the AC, 79.3% (157/198) of recorded neurons showed responses to electrical stimulation of the hippocampal CA1 area. Presumed pyramidal neurons were excited, while intermediate neurons were inhibited after electrical stimulation of the hippocampus. Conclusions: The study shows that the hippocampus is excited in SA-induced tinnitus, and stimulation of hippocampus could modulate neuronal excitability of the AC. The hippocampus is involved in tinnitus and may also have a regulatory effect on the neural center.