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Abstract

Manganese (Mn)-Enhanced MRI (MEMRI) has been proposed as a method to visualize neuronal activity in animals, taking advantage of the permeability of voltage-gated calcium channels to paramagnetic Mn2+. We tested the sensitivity of MEMRI to detect neuronal activation in the mouse auditory system, imaging mice with T1-weighted MRI at defined time points after intra-peritoneal (IP) injection of MnCl2 (0.2-mmol/kg body weight) and exposure to repetitive auditory stimulation. This easily-implemented protocol resulted in significant (10-15\%) MEMRI enhancement in the auditory inferior colliculus (IC) compared to mice with conductive hearing loss, as well as detectable enhancement in the medial geniculate nucleus and primary auditory cortex, but not in the non-auditory striatum. In an attempt to eliminate the problem of inter-animal variability, we also performed MEMRI following unilateral conductive hearing loss, comparing enhancement patterns ipsi- and contra-lateral to the functional ear after repetitive auditory stimulation of variable duration. Preliminary results showed clear enhancement of the cochlear nucleus (CN) ipsilateral to the functional ear, but the relative difference between ipsi- contralateral IC is quite variable at the post-surgical times examined. We are currently exploring a variety of protocols, altering the MnCl2 dose, as well as the timing and acoustic characteristics of the auditory stimuli, in order to optimize MEMRI enhancement in auditory brain regions. These studies provide evidence of the efficacy of MEMRI to detect accumulated neural activity in the mouse brain, and also indicate the potential of this novel non-invasive method to quantify auditory system plasticity during normal development and associated with deafness.