1pAB6 – Long-lasting suppression of spontaneous firing in inferior colliculus neurons: implication to the residual inhibition of tinnitus

A.V. Galazyuk – agalaz@neomed.edu
Northeast Ohio Medical University

Popular version of poster 1pAB6
Presented Monday morning, November 2, 2015, 3:25 PM – 3:45 PM, City Terrace 9
170th ASA Meeting, Jacksonville

More than one hundred years ago, US clinician James Spalding first described an interesting phenomenon when he observed tinnitus patients suffering from perceived phantom ringing [1]. Many of his patients reported that a loud, long-lasting sound produced by violin or piano made their tinnitus disappear for about a minute after the sound was presented. Nearly 70 years later, the first scientific study was conducted to investigate how this phenomenon, termed residual inhibition, is able to provide tinnitus relief [2]. Further research into this phenomenon has been conducted to understand the basic properties of this “inhibition of ringing” and to identify what sounds are most effective at producing the residual inhibition [3].

The research indicated that indeed, residual inhibition is an internal mechanism for temporary tinnitus suppression. However, at present, little is known about the neural mechanisms underlying residual inhibition. Increased knowledge about residual inhibition may not only shed light on the cause of tinnitus, but also may open an opportunity to develop an effective tinnitus treatment.

For the last four years we have studied a fascinating phenomenon of sound processing in neurons of the auditory system that may provide an explanation of what causes the residual inhibition in tinnitus patients. After presenting a sound to a normal hearing animal, we observed a phenomenon where firing activity of auditory neurons is suppressed [4, 5]. There are several striking similarities between this suppression in the normal auditory system and residual inhibition observed in tinnitus patients:

  1. Relatively loud sounds trigger both the neuronal firing suppression and residual inhibition.
  2. Both the suppression and residual inhibition last for the same amount of time after a sound, and increasing the duration of the sound makes both phenomena last longer.
  3. Simple tones produce more robust suppression and residual inhibition compared to complex sounds or noises.
  4. Multiple attempts to induce suppression or residual inhibition within a short timeframe make both much weaker.

These similarities make us believe that the normal sound-induced suppression of spontaneous firing is an underlying mechanism of residual inhibition.

The most unexpected outcome from our research is that the phenomenon of residual inhibition, which focuses on tinnitus patients, appears to be a natural feature of sound processing, because suppression was observed in both the normal hearing mice and in mice with tinnitus. If so, why is it that people with tinnitus experience residual inhibition whereas those without tinnitus do not?

It is well known that hyperactivity in auditory regions of the brain has been linked to tinnitus, meaning that in tinnitus, auditory neurons have elevated spontaneous firing rates [6]. The brain then interprets this hyperactivity as phantom sound. Therefore, suppression of this increased activity by a loud sound should lead to elimination or suppression of tinnitus. Normal hearing people also have this suppression occurring after loud sounds. However spontaneous firing of their auditory neurons remains low enough that they never perceive the phantom ringing that tinnitus sufferers do. Thus, even though there is suppression of neuronal firing by loud sounds in normal hearing people, it is not perceived.

Most importantly, our research has helped us identify a group of drugs that can alter this suppression response [5], as well as the spontaneous firing of the auditory neurons responsible for tinnitus. These drugs will be further investigated in our future research to develop effective tinnitus treatments.

This research was supported by the research grant RO1 DC011330 from the National Institute on Deafness and Other Communication Disorders of the U.S. Public Health Service.

[1] Spalding J.A. (1903). Tinnitus, with a plea for its more accurate musical notation. Archives of Otology, 32(4), 263-272.

[2] Feldmann H. (1971). Homolateral and contralateral masking of tinnitus by noise-bands and by pure tones. International Journal of Audiology, 10(3), 138-144.

[3] Roberts L.E. (2007). Residual inhibition. Progress in Brain Research, Tinnitus: Pathophysiology and Treatment, Elsevier, 166, 487-495.

[4] Voytenko SV, Galazyuk AV. (2010) Suppression of spontaneous firing in inferior colliculus neurons during sound processing. Neuroscience 165: 1490-1500.

[5] Voytenko SV, Galazyuk AV (2011) mGluRs modulate neuronal firing in the auditory midbrain. Neurosci Lett. 492: 145-149

[6] Eggermont JJ, Roberts LE. (2015) Tinnitus: animal models and findings in humans. Cell Tissue Res. 361: 311-336.