Kelsey L Anbuhl - US grants

DESCRIPTION (provided by applicant): Chronic ear infections resulting in a conductive hearing loss (CHL) during development can produce long-term deficits in auditory functions, including those involved with binaural hearing. These include impairment in locating sounds in space, detecting sounds in noisy environments, as well as acquisition of speech and language- all tasks that require the proper integration of information from both ears. In particular, the cue to sound location, which include interaural time (ITD) and level (ILD) difference cues, rely heavily on the proper input of sound information from both ears. Since CHL can attenuate and delay incoming sounds, the cues to sound location can thus be effectively altered. The presence of a CHL during developmental sensitive periods early in life may result in the binaural auditory system adapting to altered binaural cues to location instead of the normal cues, thus providing a possible basis for the persistent spatial hearing problems observed clinically in children. The exact mechanism underlying these persistent effects, however, is not entirely known. Several animal studies have attempted to elucidate the central mechanisms in the developing auditory system, yet few have comprehensively examined the long-term behavioral consequences of early CHL, and none have fully examined its effects on neural information processing of cues to sound location. Therefore, the main goal of this research is to understand the effects of early CHL on (1) behavioral sound localization ability and (2) information processing by neurons sensitive to sound location. Towards these goals, the Specific Aims of the proposed research are to (1) assess behavioral sound localization ability in adult guinea pigs reared with a unilateral CHL and (2) to evaluate the information processing capabilities of neurons in the inferior colliculus (IC) in the same animals reared with a unilateral CHL. Experiments will integrate both behavior and in vivo electrophysiological techniques to jointly assess the effects of early CHL on the binaural auditory system. We hypothesize that early CHL will result in persistent sound localization deficits relative to normal control animals, as well as an impairment in neural information processing of the ILD cue to sound location. In general, we expect greater behavioral deficits to be associated with a reduction in ILD information processing, and that this may provide a possible basis for the persistent spatial hearing deficits observed in children who experienced chronic ear infections early in development. The proposed work is specifically designed to support the mission of NIDCD by advancing the basic understanding of the developing binaural auditory system with clinical relevance to childhood hearing disorders.

PROJECT SUMMARY Experimental studies of developmental hearing loss (HL) typically focus on a critical period (CP) during which sensory deprivation can permanently disrupt neural function. However, childhood HL often emerges progressively after birth and extends through adolescence, leading to significant perceptual deficits. Furthermore, the magnitude of these deficits increases with longer periods of undetected HL. This suggests that auditory function remains vulnerable to HL after a CP has ended, and implicates HL duration as the key independent variable. However, the impact of developmental HL that occurs after the CP is poorly understood. Therefore, the goal of this proposal is to study the effect of HL on neural and behavioral processing during a clinically relevant period that extends through sexual maturation. An experimental paradigm will be used that allows one to parse peripheral and central mechanisms: transient earplug insertion which, when removed, leave the periphery undamaged at the time of testing. This proposal will address the core hypothesis that developmental HL induced after the critical period can disrupt cellular properties in the auditory cortex when the duration is sufficiently long, thereby impairing auditory perception and cortical encoding. There are two experimental Aims. Specific Aim 1 will determine whether long duration HL induced after the CP permanently disrupts auditory perception. Bilateral earplugs will be used to induce HL at two postnatal ages, beginning within the CP or after it ends, and extending through sexual maturity. After earplug removal and recovery of normal audiometric thresholds, animals will be trained and tested on an amplitude modulation (AM) detection task using an aversive Go/Nogo procedure. AM detection thresholds will be measured from psychometric functions and compared between HL animals and littermate controls. Auditory brainstem responses will be collected to determine whether long duration developmental HL induces changes to the auditory brainstem. Specific Aim 2 will determine whether long duration HL induced after the CP alters auditory cortex cellular properties, thereby diminishing the sensory encoding of AM stimuli during a detection task. Whole-cell recordings will be obtained from auditory cortex layer 2/3 pyramidal neurons to examine cortical synaptic and firing properties. Auditory cortex neuron responses will be recorded from chronically implanted 64 channel electrode arrays as awake- behaving animals perform the AM detection task. Neural responses to AM will be used to calculate neurometric functions that can be directly compared to behavioral performance, as well as between HL and control animals. Together, these experiments will reveal whether CNS cellular mechanisms remain vulnerable to developmental deprivation even after the CP ends, and will provide a new understanding of HL that extends into adolescence.