(from the application): The proposed research will examine the physiological and anatomical plasticity in the central and peripheral auditory systems following the removal of restricted (1 mm) spiral ganglion (SG) sectors in adult and newborn cats. Such lesions produce focal, highly restricted hearing losses without changing the overall tuning or sensitivity of the basilar membrane and allow the acute effects of focal hearing losses to be determined and compared to their chronic effects. In the proposed experiments we will determine the physiological effects by mapping the tonotopic organization of the inferior colliculus (IC) and primary auditory cortex (AI) before, immediately after, and long after restricted SG lesions both unilateral and bilateral. Our data demonstrate that acute unilateral lesions result in immediate alterations in the tonotopic organization of IC and AI neurons; they produce expansions of representations of acoustic edge frequencies. These expansions are comparable to those in published studies using chronic lesions and indicate that some of that reorganization occurs immediately (within minutes of the lesion) before any anatomical or experience-dependent changes can occur. We will determine the anatomical effects of SG lesions in adults lesioned adults or as neonates by making focal injections of direct (e.g., neurobiotin) and transsynaptic (e.g. Herpes simplex virus) tracers into intact sectors of the SG and labeling not only the direct projections of SG neurons but also their indirect (transsynaptic) projections. Previous experiments suggest that direct projections will be most profoundly altered after neonatal lesions, but the effects of both chronic adult and neonatal lesions on transsynaptic projecions, have never before been described and will be of major importance. An understanding of the critical role sensory input plays in the development and maintenance of auditory system organization is essential to any analysis of auditory function. These studies provide insight into the processes by which the auditory nervous system accommodates early acquired as well as late-onset hearing losses. They also provide insight into the time course and nature of the topographic spread of ( herpes viruses within the auditory system, the major cause of congenital deafness in humans.
