Vulnerability to Hearing Loss After the Developmental Critical Period

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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.