Mapping Auditory Brain Function with Mn-Enhanced MRI

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DESCRIPTION (provided by applicant): Functional neuroimaging methods for mapping neural activity in the mouse brain are required to analyze altered brain function in genetically-engineered mice with defined neuroanatomical and/or neurological defects. In larger rodents and primates, including humans, functional magnetic resonance imaging (fMRI) has been used increasingly to map brain activity in the major sensory systems. However, effective fMRI approaches have been difficult to implement in mice because of the high spatial resolution requirements and the presence of significant susceptibility artifacts at the high magnetic fields used for mouse MRI. Among sensory brain regions, the auditory system has been difficult to study with fMRI in mice or larger mammals because of severe susceptibility artifacts in the lower auditory centers and because of the inherent difficulties in uncoupling the auditory response to a defined acoustic stimulus from the response to the background noise produced by the MRI gradient coils. We have recently investigated a Manganese (Mn)-Enhanced MRI (MEMRI) method with the potential to provide high resolution maps of auditory brain activity induced by defined acoustic stimulation in awake behaving mice outside the magnet. Our preliminary results show that sound-induced neural activity in auditory centers of the mouse brain can be detected with MEMRI, and that altered patterns of enhancement/activity can be quantified in mice with conductive hearing loss. The broad goals of this project are to further develop these approaches, optimizing MEMRI protocols for mapping auditory neural activity in normal and deafened mice, enabling in vivo brain imaging studies of the development and plasticity of the auditory mouse brain. The specific aims are: 1) To establish an optimal MEMRI protocol to detect neural activity in the mouse auditory midbrain. 2) To establish the spatial / frequency resolution of MEMRI for auditory brain mapping in the mouse. 3) To define and characterize altered patterns of MEMRI enhancement in unilaterally deaf mice. These studies will form the basis for future brain mapping investigations in normal and genetically-engineered mice, providing much needed new neuroimaging tools for studying the genetic pathways underlying normal hearing and hearing disorders.