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Abstract

MEMRI was applied for mapping brain activity in rats subjected to spatial learning. MnCl2 was used as a T1-shortening contrast agent that increases the signal intensity at the locations where Mn2+ ions accumulate. Mn2+ enter the cells via voltage-gated calcium channels and its accumulation in the brain is proportional to neural activity. Rats were implanted (IP) with Mn-loaded osmotic pumps (0.5mmol/kg/200microL) that provided a constant and slow release of Mn (1microL/h) over 14 days, and they were subjected to three experimental conditions. The first group was trained to perform a T-maze delayed alternation task. During the sample trial the two maze arms (start and reward) were available and the side of reward location varied randomly across ten daily trials. During the choice trial all three maze arms were open and the reward was available on the alternative maze arm only. There was a 30-sec delay between the sample and the choice trials. On average, after 10 days of training, the rats reached an asymptotic performance with 90 correct choices. Two other groups of rats served as controls. Sedentary rats were kept in the home cage for the entire duration of training. Pseudo-trained rats were subjected to the identical procedure on the maze except for the alternation rule. Rats received the reward regardless of their choice of a particular maze arm. After 14 days all rats were scanned in 7T magnet under isoflurane anesthesia. Statistical maps of the functional brain activation were generated from group paired comparisons using t-test. Exposure to the maze resulted in elevated accumulation of Mn2+ in hippocampus. Rats, trained to perform the alternation task, showed additional activation of primary sensory areas (visual, auditory, and somatosensory). MEMRI allowed visualizing learning-related brain activity in freely behaving animals. This technique can be used for tracking the dynamic reorganization of neural networks at multiple time points in the same animal.