Neural plasticity in the mouse inferior colliculus: relationship to hearing loss, augmented acoustic stimulation, and prepulse inhibition
Introduction
Mice of the C57BL/6J (C57) and DBA/2J (DBA) inbred strains undergo genetically determined, progressive sensorineural hearing loss (Erway et al., 1993, Henry and Chole, 1980, Hunter and Willott, 1987, Li and Borg, 1991, Mikaelian, 1979, Parham et al., 1997, Ralls, 1967, Willott, 1981, Willott, 1986, Willott et al., 1995).
Both strains provide models with which to study central hearing loss-induced (HLI) plasticity (e.g. Willott, 1996). The present paper focuses on several related issues: how HLI plasticity in the inferior colliculus (IC) is revealed by neural responses evoked by 70-dB SPL tones; how the changes in the neural responses are manifested behaviorally as indicated by prepulse inhibition (PPI), a behavioral response to 70-dB tones; and how IC responses in DBA mice are related to improvements in PPI resulting from exposure to an augmented acoustic environment (AAE).
Abnormal response properties are exhibited by neurons in the IC of both C57 and DBA mice with high-frequency hearing loss. Most notably for the present discussion, tonotopic organization of the IC is substantially altered in both strains (Willott, 1981, Willott, 1984, Willott, 1986, Willott, 1996). In normal-hearing mice (as in other mammals), neurons in the dorsal–dorsolateral IC have sensitive thresholds and vigorous suprathreshold responses to low frequency sounds. At increasingly ventral–ventromedial locations the optimal frequencies become increasingly higher. After basal cochlear degeneration has occurred in DBA and C57 mice, this is no longer possible because severe high-frequency hearing loss removes the normal input to ventrally located neurons. However, the ventral neurons do not remain silent, but rather, their thresholds for low- and middle-frequency sounds become more similar to those in more dorsal IC regions. The tonotopic alteration of frequency threshold maps is one aspect of HLI plasticity, and has been observed in the central auditory system of several other species in which hearing loss has been experimentally-induced during adulthood (Calford et al., 1993, Rajan et al., 1993, Robertson and Irvine, 1989, Schwaber et al., 1993).
Whereas both DBA and C57 mice with hearing loss exhibit abnormal tonotopic organization, there are some important differences between the two strains. C57 mice have good hearing as young adults (1–2 months of age) and exhibit a change in IC organization as high-frequency hearing loss gradually ensues over the next few months (Willott, 1986). DBA mice, however, have poor sensitivity to high frequencies (>16 kHz) even at 3 weeks of age, and abnormal tonotopic organization is already observed (Willott et al., 1982). Thus, tonotopic organization does not change from normal to abnormal as it does in C57 mice. The other important strain difference is that progressive hearing loss is much more rapid in DBA mice. At 2 months of age, ABR tone thresholds of DBA mice are roughly equivalent to those of 12-month-old C57 mice. Thresholds for tones ≥16 kHz are greater than 70-dB SPL; thresholds for 12-kHz tones are elevated to about 55–60 dB; thresholds for 4 and 8 kHz are about 50 dB. Thus, DBA mice provide an animal model for pre-adult onset, rapid hearing loss, whereas C57 mice have adult-onset, gradual hearing loss.
Most of the studies cited above have measured thresholds and tuning curves to demonstrate HLI plasticity. For the present paper, HLI plasticity in the two mouse strains was evaluated by determining how the IC responds to tones of 70-dB SPL. These stimuli were chosen in order to correlate IC responses with tones used in PPI experiments.
In our laboratory, we have been employing the PPI paradigm as one way to determine whether tonotopic abnormalities have an impact on hearing and/or auditory behaviors. As we use PPI, a 70-dB SPL tone is presented 100 ms prior to an intense startle stimulus, and this results in reduced startle amplitude (‘inhibition’). Studies on human subjects have shown that the magnitude of PPI reflects the behavioral ‘salience’ of the prepulse tones (Hoffman and Ison, 1980). Importantly, the neural pathways mediating PPI have been studied, and it has been established that the IC plays a crucial role in the processing of prepulses and their ability to inhibit the startle response circuit. For example, lesions of the IC reduce or abolish PPI, whereas electrical stimulation of the IC produces PPI (Fox, 1979, Leitner and Cohen, 1985, Li et al., 1998a, Li et al., 1998b). It follows, therefore, that changes in the responses of IC neurons to tones have the potential to modulate PPI, when those tones are used as prepulses. Indeed, studies of C57 mice have shown that the magnitude of PPI changes in a manner that is correlated with hearing loss and HLI plasticity (Carlson and Willott, 1996, Willott and Carlson, 1995, Willott et al., 1994).
The present paper compared data sets for IC responses evoked by 70-dB tones and for PPI using 70-dB tones as prepulses. The goal was to elucidate the functional relationship between IC responses and PPI in the context of hearing loss and central auditory system plasticity.
We have demonstrated that progressive hearing loss and PPI in DBA mice are modulated by exposing them for 12 h nightly to repetitive bursts of a moderately intense broadband noise AAE. The AAE retards the progressive elevation of high-frequency thresholds, presumably by affecting the cochlea (Turner and Willott, 1998, Willott and Turner, 1999). AAE exposure also improves PPI (stronger inhibition of the startle response), and this AAE effect may represent a form of stimulation-induced central plasticity on top of HLI plasticity (e.g. in the IC). Thus, the present paper compared AAE-exposed and non-exposed DBA mice to provide another avenue to examine the relationship between PPI and IC responses when plasticity has occurred.
Section snippets
Materials and methods
The methods have been described in detail in previous papers and will only be outlined here. C57 and DBA mice of either sex were obtained from the Northern Illinois University Psychology Department rodent colony.
Tonotopic organization
In this paper, we were primarily interested in the processing of 70-dB SPL tones, used in the PPI experiments. Thus, tonotopic organization was evaluated with respect to the proportion of multiple-unit recording sites responding to 70-dB tones of 4, 8, 12, 16, 24, and 32 kHz. The dorsoventral locations were divided into thirds: dorsal (0–500 μm), middle (501–1000 μm), and >1000 μm (usually to a maximum of about 1500 μm).
Fig. 1 (from data presented in a different form in Willott, 1984, Willott,
Discussion
The data reviewed here indicate that the processing of 70-dB tones is abnormal in the IC of C57 and DBA mice that have high-frequency hearing loss. In both strains, the occurrence of high-frequency hearing loss was accompanied by disruption of the normal dorsoventral, low-to-high progression of optimal frequency representation. In the ventral IC, lower frequency tones evoked responses in an abnormally large percentage of recording sites. Thus, HLI plasticity was evident in suprathreshold
Acknowledgements
This research was supported by NIH Grant R37 AG07554.
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Present address: University of Tennessee Martin, Department of Psychology, Martin, TN 38238-505, USA.