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In vivo auditory brain mapping in mice with Mn-enhanced MRI

Abstract

There are currently no noninvasive imaging methods available for auditory brain mapping in mice, despite the increasing use of genetically engineered mice to study auditory brain development and hearing loss. We developed a manganese-enhanced MRI (MEMRI) method to map regions of accumulated sound-evoked activity in awake, normally behaving mice. To demonstrate its utility for high-resolution (100-μm) brain mapping, we used MEMRI to show the tonotopic organization of the mouse inferior colliculus. To test its efficacy in an experimental setting, we acquired data from mice experiencing unilateral conductive hearing loss at different ages. Larger and persistent changes in auditory brainstem activity resulted when hearing loss occurred before the onset of hearing, showing that early hearing loss biases the response toward the functional ear. Thus, MEMRI provides a sensitive and effective method for mapping the mouse auditory brainstem and has great potential for a range of functional neuroimaging studies in normal and mutant mice.

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Figure 1: Mn-enhanced MRI (MEMRI) of the mouse brain under normal conditions.
Figure 2: Brain regions were analyzed from volumetric in vivo MRI data.
Figure 3: MEMRI enhancement in brainstem auditory nuclei was altered in mice with CHL.
Figure 4: MEMRI was used to map the tonotopic organization of the mouse IC.
Figure 5: MEMRI can be used for longitudinal imaging studies.
Figure 6: MEMRI demonstrates differences in sound-evoked activity in mice experiencing CHL at distinct developmental stages.

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Acknowledgements

This research was supported by US National Institutes of Health grants NS38461 and DC06892 (D.H.T.). We thank A. Joyner and G. Fishell (Skirball Institute, NYU School of Medicine) for critical review of this paper. We also thank C. Moreno and D. Rubin for technical assistance in the initial stages of this project and J. Lefman for advice on the volumetric display and analysis routines used for tonotopic mapping. Finally, D.H.T. thanks R. Menon (Robarts Institute, University of Western Ontario) for originally drawing his attention to the potential of MEMRI for activity mapping.

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Correspondence to Daniel H Turnbull.

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Supplementary information

Supplementary Fig. 1

Spectra of sound stimuli. (PDF 1115 kb)

Supplementary Fig. 2

Sound stimulus versus quiet. (PDF 3451 kb)

Supplementary Fig. 3

Longitudinal MEMRI results. (PDF 4884 kb)

Supplementary Note (PDF 302 kb)

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Yu, X., Wadghiri, Y., Sanes, D. et al. In vivo auditory brain mapping in mice with Mn-enhanced MRI. Nat Neurosci 8, 961–968 (2005). https://doi.org/10.1038/nn1477

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