Morphological and functional midbrain phenotypes in Fibroblast Growth Factor 17 mutant mice detected by Mn-enhanced MRI

Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
NeuroImage (Impact Factor: 6.36). 02/2011; 56(3):1251-8. DOI: 10.1016/j.neuroimage.2011.02.068
Source: PubMed


With increasing efforts to develop and utilize mouse models of a variety of neuro-developmental diseases, there is an urgent need for sensitive neuroimaging methods that enable in vivo analysis of subtle alterations in brain anatomy and function in mice. Previous studies have shown that the brains of Fibroblast Growth Factor 17 null mutants (Fgf17(-/-)) have anatomical abnormalities in the inferior colliculus (IC)-the auditory midbrain-and minor foliation defects in the cerebellum. In addition, changes in the expression domains of several cortical patterning genes were detected, without overt changes in forebrain morphology. Recently, it has also been reported that Fgf17(-/-) mutants have abnormal vocalization and social behaviors, phenotypes that could reflect molecular changes in the cortex and/or altered auditory processing / perception in these mice. We used manganese (Mn)-enhanced magnetic resonance imaging (MEMRI) to analyze the anatomical phenotype of Fgf17(-/-) mutants in more detail than achieved previously, detecting changes in IC, cerebellum, olfactory bulb, hypothalamus and frontal cortex. We also used MEMRI to characterize sound-evoked activity patterns, demonstrating a significant reduction of the active IC volume in Fgf17(-/-) mice. Furthermore, tone-specific (16- and 40-kHz) activity patterns in the IC of Fgf17(-/-) mice were observed to be largely overlapping, in contrast to the normal pattern, separated along the dorsal-ventral axis. These results demonstrate that Fgf17 plays important roles in both the anatomical and functional development of the auditory midbrain, and show the utility of MEMRI for in vivo analyses of mutant mice with subtle brain defects.

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Available from: Brian Nieman, Aug 26, 2014
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    • "malies which focus on central neurological manifestations of inner hair cell dysfunction in Bassoon mutant mice where , mod - erate hearing loss and seizures are manifest as part of the disease expression ( Altrock et al . , 2003 ; Angenstein et al . , 2007 ) , in phe - notyping central auditory defects in fibroblast growth factor 17 mutant mice ( Yu et al . , 2011 ) , and more recently , to the area of tinnitus . Experimental evidence showing that MEMRI can be used to localize endogenously generated neural hyperactivity in rats having behavioral evidence of tinnitus induced by noise exposure and salicylate administration opens up a whole new research domain for studying phantom - like perceptions"
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    ABSTRACT: Manganese enhanced magnetic resonance imaging (MEMRI) is a method used primarily in basic science experiments to advance the understanding of information processing in central nervous system pathways. With this mechanistic approach, manganese (Mn2+) acts as a calcium surrogate, whereby voltage-gated calcium channels allow for activity driven entry of Mn2+ into neurons. The detection and quantification of neuronal activity via Mn2+ accumulation is facilitated by “hemodynamic-independent contrast” using high resolution MRI scans. This review emphasizes initial efforts to-date in the development and application of MEMRI for evaluating tinnitus (the perception of sound in the absence of overt acoustic stimulation). Perspectives from leaders in the field highlight MEMRI related studies by comparing and contrasting this technique when tinnitus is induced by high-level noise exposure and salicylate administration. Together, these studies underscore the considerable potential of MEMRI for advancing the field of auditory neuroscience in general and tinnitus research in particular. Because of the technical and functional gaps that are filled by this method and the prospect that human studies are on the near horizon, MEMRI should be of considerable interest to the auditory research community.
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