Imaging the plasticity of the central auditory system on the cellular and molecular level

Abstract

Abstract Objective: It has been debated for decades if and to what extent the mature central nervous system of mammals is capable to respond to altered sensory use and function with changes of structure and function. We attempted to shed new light on the neuroplastic potential of the central auditory system, using light and electron microscopic techniques to explore it on the levels of cells (both neurons and glia), synapses, selected molecular components of the tissue, and the spatiotemporal relationship among these following the induction of changed patterns of sensory activity. Study Design: Working in an animal model, we induced two modifications to normal auditory signalling in the adult rat brain. Through unilateral cochleotomy, we caused a total primary deafferentation in the cochlear nucleus and abolished all sensory input through the ear. By electrical intracochlear stimulation (EIS) we substituted normal sensory signalling by an artificial input that was under complete temporal control. Results: Following cochlear ablation, we observed a complex succession of molecular and cellular changes. They included a massive expression and redistribution of glial as well as neuronal markers, and resulted in newly formed synaptic contacts that grow in from the superior olivary complex. Acute EIS has affects on the gene expression throughout the ascending auditory system within hours. With gradually extended stimulation periods, we observed a variety of other tissue constituents to change, eventually also including GAP-43, indicator of nascent synaptic contacts. Conclusion: The adult mammalian brainstem is capable of extensive remodelling on the level of synapse number, synapse growth, and consequential network dynamics under the influence of altered patterns of sensory stimulation. These changes include cellular correlates of learning and memory. It is a challenge for auditory neuroscience and the rehabilitation of the hearing-impaired to learn to exploit this potential to the limit.