Cochlear Physiological Potentials

The endocochlear potential measures the voltage potential in scala media, which contains the K+ rich endolymph in the cochlea. This fluid bathes the tops of the cochlear inner and outer hair cells, and plays an important role in hair cell transduction of acoustic sound waves in the inner ear into the code of the nervous system that gets sent to the brain via the nerve fibers of the auditory division of the eighth cranial nerve. R.A. Schmiedt and coworkers have measured this potential in vivo, in animal models of different ages (e.g., gerbils), and found that the magnitude of this electrical potential declines with normal aging (Schmiedt and Schulte, 1992; Schulte and Schmiedt, 1992; Schmiedt, 1993). This decline is analogous to a car battery slowly going dead over time. As this battery-like voltage declines with age, the sensitivity of the inner ear decreases as measured by cochlear compound action potentials and the thresholds of auditory-nerve fibers, and the overall sensitivity of the auditory system becomes impaired (Schmiedt et al., 1990; Hellstrom and Schmiedt, 1990, 1991).


J.R. Ison and colleagues have pioneered the use of the behavioral psychology paradigm, known as the inhibition of the startle reflex, as a fast and reliable measure of the hearing capabilities in animals, especially for studies of the aging auditory system and determination of its neural bases (Hoffman and Ison, 1980; Ison, 1982; Ison and Hoffman, 1983; Young and Fechter, 1983; Ison and Bowen, 2000). This procedure is carried out by taking advantage of the fact that mammals will respond quickly and in an unbiased way when presented with a loud click, via a jump in the case of rodents, or with an eye blink in larger mammals including humans. The click would be akin to snapping your fingers near your ear. Ison and coworkers have demonstrated that when a warning sound is presented just before the startle stimulus (loud click), the amplitude of the rodent jump or human eye blink will be attenuated proportionately to the effectiveness or detectability of the warning sound (prepulse). This reliable, efficient measure of auditory processing is called prepulse inhibition. Ison's team has utilized this effectively to evaluate the temporal processing capabilities of the aging auditory system using gaps or decrements in ongoing sounds, including tones or wideband noise, as prepulse inhibition stimuli (Walton et al., 1997; Ison et al., 1997, 1998, 2001; Barsz et al., 2002; Allen et al., 2003). For example, in CBA mice the gap detection threshold significantly declines with age, and these temporal processing deficits mirror neurophysiological gap threshold changes recorded at the level of the auditory midbrain-inferior colliculus, described in more detail later.


Ison's research group has more recently developed a variation on the inhibition of startle research paradigm for measuring spatial processing in mice as a function of age (Allen et al., 2004). Here, a mouse assumes a standard spatial position and orientation in the inhibition of startle measurement cage. When in the calibrated place, a prepulse inhibition auditory stimulus is presented from one of several possible spatial positions. By varying the location of the prepulse inhibition sound in a calibrated manner from trial to trial, auditory spatial processing capabilities of mice can be measured as a function of age and stimulus type. Indeed, the ability to correctly localize sounds in space, particularly the azimuth, declines significantly in the aging mouse.


As presented earlier in the human sections, presbycusis involves a loss of sensitivity to sound, temporal processing deficits, and spatial tuning degradations, all of which can contribute to a difficulty understanding speech by the elderly, particularly in noisy situations. Behavioral and evoked potential work in animal models, such as mice and other rodents, confirms that most mammals develop age-related hearing problems with many similarities to the human condition, such as spatial and temporal processing deficits, that are confounded by complex acoustic environments such as those containing background noise. Physiological recordings in the auditory brainstem give insights to the neural mechanisms that may underlie these perceptual and behavioral findings.

Willott and coworkers were the first to systematically investigate changes in tonotopic or cochleotopic organizations of brainstem auditory nuclei as the high-frequency hearing loss characteristic of presbycusis progresses in mice (Willott et al., 1985, 1988a, b; Willott, 1986, 1991). Tonotopic or cochleotopic organization refers to the fact that the major cell groups, or nuclei, of the brainstem auditory system have frequency organizations that originate in the cochlear spiral, where high frequency nerve cells are in one location, then middle frequency, then low frequency nerve cells in another, much like the keys on a piano. Tonotopically organized nerve cell pathways connect the cochlea to the cochlear nucleus, the first major nucleus of the central auditory system, and these pathways continue in an organized manner up through the auditory cortex, with sound information being processed at each step along the way. In aging, when the basal portions of the cochlea lose a significant number of hair cells with age, there is a concomitant loss of high frequency pathways and nerve cells in the central auditory system. Willott and colleagues discovered that

Figure 76.6 Single nerve cells in the auditory midbrain-inferior colliculus of unanaesthetized CBA mice have longer gap thresholds in old age, compared to young adults. The proportion of single nerve cells possessing minimum gap thresholds (MGTs) ranging from 1 to >11 msec are shown for young adult mice, hatched bars (N=78 cells), and for old mice, solid bars (N=108 cells). Note that the data in this histogram indicate a distribution of single-nerve cell gap thresholds to longer gaps in old age. From Walton et al. (1998), with permission.

when there is a loss of high frequency pathways to the auditory midbrain-inferior colliculus, the ventral portions of this region start responding to lower frequencies in the absence of the normal high frequency inputs.

Walton and coworkers have made extensive single nerve cell recordings in the inferior colliculus of old CBA mice, who still have reasonably good auditory sensitivity in old age. They have discovered that at suprathreshold sound levels where single nerve cells still give good responses, temporal processing problems can occur during aging that increase gap detection thresholds and distort responses to the onset and waveforms of biologically relevant sounds (Walton et al., 1997, 1998, 2002; Simon et al., 2004). Examples of some of these changes in the responses of single nerve cells are provided in Figures 76.6 and 76.7.


Not surprisingly, there are neuroanatomical and neuro-chemical changes occurring in the auditory system with age that correlate and may underlie the behavioral and functional declines that have been discussed so far. A variety of anatomical and biochemical methodologies have been employed to examine these aspects of age-related hearing loss, and in most cases, animal models have been effectively employed.

D.M. Caspary and his colleagues conducted a comprehensive series of anatomical and biochemical experiments on the GABA system in the auditory midbrain. GABA is one of the two most prominent inhibitory neuro-transmitters in the central auditory system. Caspary's group put forth some convincing evidence that there is an age-related down-regulation of the main GABA

neurotransmitter system of the auditory midbrain (Caspary et al., 1990, 1995, 1999; Helfert et al., 1999). This loss of inhibition is consistent with some of the neurophysiological functional data concerning the disruption of complex sound processing in quiet and background noise characteristic of presbycusis.

Frisina and coworkers have studied certain anatomical aspects that accompany the age-related temporal processing deficits discovered by Walton's team as presented earlier. For instance, the same regions of the auditory midbrain that manifest the age-dependent temporal processing disorders also show changes in intracellular calcium regulation as investigated using immunocyto-chemical antibody labeling methodologies (Zettel et al., 1997, 2001). Calbindin and calretinin are two of the most important calcium-binding proteins in the brain involved in intracellular calcium regulation critical for neurotrans-mitter synthesis and release. Calbindin was found to decline with age in the inferior colliculus, and calretinin increased with age, but only in mice with good hearing in old age. Mice deafened as young adults did not show this upregulation, indicating that it was dependent on the sound-evoked activity being present. Frisina's group also found that certain neural input pathways from the contralateral cochlear nucleus and superior olivary complex in the brainstem auditory system to the inferior colliculus showed an age-related decline using neural tract-tracing techniques (Frisina and Walton, 2001).


It is evident that a variety of methodologies have been effectively utilized to investigate age-related hearing loss in human listeners and for animal models. Exciting future possibilities include assessing hearing improvements using

All Stimulus Intensity Sample Groups

All Stimulus Intensity Sample Groups

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