Exploring hearing loss and plastic adjustments in the dorsal cochlear nucleus

Acoustic over exposure (AOE) triggers hearing loss and tinnitus but cellular mechanisms underlying those auditory defects are still poorly understood. This thesis explores the changes of excitability produced by AOE in identified cells of the rat dorsal cochlear nucleus (DCN) within the auditory brainstem. A development of a method combining Golgi silver impregnation with Nissl staining allowed study of the morphology and the distribution of the main DCN neuronal subtypes within slices containing the DCN. Whole cell patch clamp recordings allowed characterisation of the distinctive electrophysiological properties of the main DCN neuronal subtypes. In vitro stimulations of auditory or multisensory synaptic inputs showed fundamental differences in terms of the principal neurones firing pattern and the role of inhibitory synaptic transmission on firing pattern. Wistar rats were exposed to loud (110 dB SPL) single tones (15 kHz) for a period of 4 hours (protocol of AOE). Non invasive auditory brainstem response recordings were performed after 3 to 4 days and showed a significant increase of the rat’s hearing threshold for frequencies above 8 kHz. Whole cell recordings performed at a similar time (3 to 4 days) after AOE, showed that AOE led to a change of the passive and the active properties of DCN interneurones and principal cells. AOE also decreased the general excitability of the cellular network and affected differently excitatory and inhibitory synaptic transmission onto principal neurones depending on whether multisensory or auditory synaptic inputs were stimulated. Computational modelling allowed simulation of the effects of AOE on principal cell firing patterns and elaboration of a general theory whereby AOE triggers shifts of hearing thresholds concomitant with plastic adjustments in the DCN network. In conclusion, an elevation of the hearing threshold accompanied by significant excitability changes within the central auditory system could represent fundamental steps towards the development of tinnitus