Long-Lasting forward Suppression of Spontaneous Firing in Auditory Neurons: Implication to the Residual Inhibition of Tinnitus.
acoustic trauma; Animals; Brain Stem – Physiology; Clinical Assessment Tools; Cochlear Nerve – Physiology; Cochlear Nerve/*physiology; Inbred CBA; Inferior Colliculi/*physiology; inferior colliculus; Male; mice; Mice; residual inhibition; Sound; Tinnitus – Physiopathology; Tinnitus/*physiopathology
Tinnitus is the perception of a sound that has no external source. Sound stimuli can suppress spontaneous firing in auditory neurons long after stimulus offset. It is unknown how changes in sound stimulus parameters affect this forward suppression. Using in vivo extracellular recording in awake mice, we found that about 40 % of spontaneously active inferior colliculus (IC) neurons exhibited forward suppression of spontaneous activity after sound offset. The duration of this suppression increased with sound duration and lasted about 40 s following a
Galazyuk A V; Voytenko S V; Longenecker R J
Journal of the Association for Research in Otolaryngology : JARO
2017
2017-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s10162-016-0601-9" target="_blank" rel="noreferrer noopener">10.1007/s10162-016-0601-9</a>
Methodological optimization of tinnitus assessment using prepulse inhibition of the acoustic startle reflex.
Acoustic Stimulation/instrumentation/*methods; Animal/physiology; Animals; Behavior; Habituation; Mice; Psychophysiologic/physiology; Reflex; Startle/*physiology; Tinnitus/*diagnosis/physiopathology
Recently prepulse inhibition of the acoustic startle reflex (ASR) became a popular technique for tinnitus assessment in laboratory animals. This method confers a significant advantage over the previously used time-consuming behavioral approaches utilizing basic mechanisms of conditioning. Although this technique has been successfully used to assess tinnitus in different laboratory animals, many of the finer details of this methodology have not been described enough to be replicated, but are critical for tinnitus assessment. Here we provide detail description of key procedures and methodological issues that provide guidance for newcomers with the process of learning to correctly apply gap detection techniques for tinnitus assessment in laboratory animals. The major categories of these issues include: refinement of hardware for best performance, optimization of stimulus parameters, behavioral considerations, and identification of optimal strategies for data analysis. This article is part of a Special Issue entitled: Tinnitus Neuroscience.
Longenecker R J; Galazyuk A V
Brain research
2012
2012-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.brainres.2012.02.067" target="_blank" rel="noreferrer noopener">10.1016/j.brainres.2012.02.067</a>
Prepulse inhibition of the acoustic startle reflex vs. auditory brainstem response for hearing assessment.
*Audiometric functions; *Hearing loss; *Mouse; *Permanent threshold shift; *Sound exposure; *Temporary threshold shift; Acoustic Stimulation/*methods; Animal; Animals; Audiometry; Auditory; Auditory Threshold/*physiology; Brain Stem/*physiology; Evoked Potentials; Hearing; Inbred CBA; Male; Mice; Models; Noise; Prepulse Inhibition/*physiology; Pure-Tone/*methods; Reflex; Startle/*physiology
The high prevalence of noise-induced and age-related hearing loss in the general population has warranted the use of animal models to study the etiology of these pathologies. Quick and accurate auditory threshold determination is a prerequisite for experimental manipulations targeting hearing loss in animal models. The standard auditory brainstem response (ABR) measurement is fairly quick and translational across species, but is limited by the need for anesthesia and a lack of perceptual assessment. The goal of this study was to develop a new method of hearing assessment utilizing prepulse inhibition (PPI) of the acoustic startle reflex, a commonly used tool that measures detection thresholds in awake animals, and can be performed on multiple animals simultaneously. We found that in control mice PPI audiometric functions are similar to both ABR and traditional operant conditioning audiograms. The hearing thresholds assessed with PPI audiometry in sound exposed mice were also similar to those detected by ABR thresholds one day after exposure. However, three months after exposure PPI threshold shifts were still evident at and near the frequency of exposure whereas ABR thresholds recovered to the pre-exposed level. In contrast, PPI audiometry and ABR wave one amplitudes detected similar losses. PPI audiometry provides a high throughput automated behavioral screening tool of hearing in awake animals. Overall, PPI audiometry and ABR assessments of the auditory system are robust techniques with distinct advantages and limitations, which when combined, can provide ample information about the functionality of the auditory system.
Longenecker R J; Alghamdi F; Rosen M J; Galazyuk A V
Hearing research
2016
2016-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.heares.2016.06.006" target="_blank" rel="noreferrer noopener">10.1016/j.heares.2016.06.006</a>
Residual inhibition: From the putative mechanisms to potential tinnitus treatment.
Neurons in various sensory systems show some level of spontaneous firing in the absence of sensory stimuli. In the auditory system spontaneous firing has been shown at all levels of the auditory pathway from spiral ganglion neurons in the cochlea to neurons of the auditory cortex. This internal "noise" is normal for the system and it does not interfere with our ability to perceive silence or analyze sound. However, this internal noise can be elevated under pathological conditions, leading to the perception of a phantom sound known as tinnitus. The efforts of many research groups, including our own, led to the development of a mechanistic understanding of this process: After cochlear insult the input to the central auditory system becomes markedly reduced. As a result, the neural activity in the central auditory system is enhanced to compensate for this reduced input. Such hyperactivity is hypothesized to be interpreted by the brain as a presence of sound. This implies that suppression of hyperactivity should reduce/eliminate tinnitus. This review explores research from our laboratory devoted to identifying the mechanism underlying residual inhibition of tinnitus, a brief suppression of tinnitus following a sound stimulus. The key mechanisms that govern neural suppression of spontaneous activity in animals closely resemble clinical psychoacoustic findings of residual inhibition (RI) observed in tinnitus patients. This suppression is mediated by metabotropic glutamate receptors (mGluRs). Lastly, drugs targeting mGluRs suppress spontaneous activity in auditory neurons and reduce/eliminate behavioral signs of tinnitus in mice. Thus, these drugs are therapeutically relevant for tinnitus suppression in humans.
Galazyuk A V; Longenecker R J; Voytenko S V; Kristaponyte I; Nelson G L
Hearing research
2019
2019-04
<a href="http://doi.org/10.1016/j.heares.2019.01.022" target="_blank" rel="noreferrer noopener">10.1016/j.heares.2019.01.022</a>