Our long-term goals are to understand neuronal mechanisms that underlie hearing in mammals. In the auditory nervous system, all acoustic information from the environment enters the brain by passing through the auditory nerve and terminating in the cochlear nucleus. The cochlear nucleus serves as the gateway to the central auditory system because it gives rise to all ascending pathways. How auditory information is processed will depend greatly on the structural organization of auditory nerve inputs. The relatively homogeneous responses of incoming auditory nerve fibers are transformed into a variety of different response patterns by the different classes of resident neurons in the cochlear nucleus. These signals are in turn transmitted to higher centers by the ascending pathways.

The spectrum of the responses depends not only upon the synaptic organization of the auditory nerve but also on intrinsic neurons and descending inputs; the types and distribution of receptors, ion channels, and G proteins; and second messengers. These features form the signaling capabilities for each cell class. In order to understand how sound is processed, there is a need to study identified cell populations, to analyze their synaptic connections, and to reveal features of their signal processing capabilities. We use electrophysiological recording methods, immunocytochemistry and pathway tracing for light and electron microscopic analyses. These methods are applied to various strains of mice with different onset times of hearing loss and transgenic mice with different pathways labeled. We will follow the pathologic reorganization of auditory pathways following hearing loss, and plan to determine the extent to which the pathology can be reversed by restoring hearing. Our studies seek to provide new knowledge toward understanding basic mechanisms of hearing and the role of hearing in the development of the central auditory system.

In Australia, it is estimated that just over 20% of the adult population suffer from hearing loss and that this number exceeds 50% for those over 65 years of age. In children, hearing loss impairs speech and language development, which in turn undermines academic achievement. In adults, it has a negative impact on employment opportunities and social functioning. Hearing loss creates social isolation that can develop into depression and early onset dementia.

Hearing is one of our special senses that allows us to detect vibrations in air and perceive them as sound. Hearing involves more than just processing the transduction of vibrations in air. Once a sound is detected, there is a need to localize the source. This task requires two ears and knowledge of head position. For animals with mobile ears, pinna orientation is important. Proprioceptive, vestibular, and visual cues are used to determine whether the organism or the sound is moving. Identification of the sound involves learning and memory, and once identified, sounds can evoke changes in affective state. For example, sounds made by a potential mate should be different from those of a predator; moreover, the brain will produce different emotional responses. Acoustic comprehension, therefore, involves the integration of many brain functions. The building blocks for this goal will be to determine functional circuits in order to gain insight on the integrative nature of acoustic processing.

Our research at the Garvan addresses normal mechanisms of hearing so that we can better understand hearing loss and its accompanying brain abnormalities. One project examines excitatory brain circuits that initiate feedback excitation. Such feedback may be a way for the brain to focus on important signals. Another project will study the pathology of synapses and alterations in inhibitory circuits that develop as a result of hearing loss. And a third project examines a feedback circuit that regulates "volume control" in the inner ear. This circuit reduces the sensitivity of the inner ear to specific sounds and may underlie selective listening, a practice that deteriorates with aging. The consequences of these kinds of changes are tied to the production of tinnitus (or ringing of the ears), an impaired ability to understand speech in noisy environments, loudness distortion, and a difficulty in using hearing devices such as hearing aids and cochlear implants. Because hearing loss cannot be remedied by amplification alone, we need to understand more about the anatomy, physiology, and genetics of brain circuits and the nature of their change. Our research will collect data that should contribute to more effective treatment strategies and perhaps a modification of current hearing aid devices for improved outcomes.