Progressive Recovery of Cortical and Midbrain Sound Feature Encoding Following Profound Cochlear Neuropathy.

Abstract

To enable the identification and localization of sounds in our environment, auditory brain centers must form representations that accurately encode distinct acoustic properties, but also integrate those properties to support a unified percept of an auditory object. These parallel operations of decomposition and integration are carried out by hierarchically organized processing regions which progressively reformat peripheral electrical impulses into signals that may be integrated into higher order brain circuits. To investigate the nature of these transformations and their vulnerability to hearing loss, I recorded extracellular responses in the auditory midbrain and cortex of awake mice. The first aim of this project was to study the multiparametric tuning characteristics of single neurons using an online stimulus optimization algorithm. Closed-loop stimulus tailoring rapidly revealed diverse multiparametric tuning, and further revealed the conservation of response sparseness between the two areas. I then tracked the recovery of central feature encoding in mice with profound cochlear neuropathy. I recorded from midbrain and cortex at two timepoints after nerve degeneration, observing a progressive recovery of responsiveness in both areas, which occurred earlier and was more robust in the cortex. Concurrently, several aspects of the once-precise temporal response properties in midbrain were persistently degraded, and classification of speech tokens in the cortex did not recover to control levels of accuracy. I hypothesize that compensatory central plasticity may support the recovery of feature encoding in the auditory pathway to a large extent, although various aspects of temporal encoding remain impaired. This may underlie the observation that some human patients with auditory neuropathy have profound deficits in speech comprehension despite having normal hearing thresholds. Finally, I tested the effect of AUT3, a novel positive modulator of the Kv3.1 potassium channel, on the encoding and classification of pulse trains and speech tokens in the midbrain. I observed that adjusting the excitability of central auditory neurons with this compound can partially restore the precision and reliability of spiking responses after hearing loss.