The activity-induced manganese-enhanced MRI (AIM-MRI) is one of the candidate methods for measuring the neuronal activity noninvasively in vivo. This method has the potential to measure the history of the neuronal activity, since the Mn
2+ can enter the active neuron through voltage-dependent Ca
2+ channels. However, it has not been clear that the relation between the neuronal activity and the accumulation of Mn
2+ in the cell. At first, we confirmed that the longitudinal relaxation time of H
+ (T
1) measured by means of MRI apparatus was related to the [Mn
2+] using the pseudo intracellular phantoms with various concentration of Mn
2+. The inverse of T
1 (1/T
1) was proportional to [Mn
2+], thus [Mn
2+] can be measured by MRI quantitatively. Next, we investigated the relation between the neuronal activity and the accumulation of Mn
2+ in the striatal GABAergic neurons using the method of the Mn
2+ quenching of Fura-2 LR, a family of fura fluorescent Ca
2+ indicators. The amount of the Ca
2+ influx was correlated to the neuronal activity evoked by tetanic stimulations with various frequencies. In the same slice preparation, the amounts of the fluorescence quench induced by the tetanic stimulations under the condition of 50 µM MnCl
2 administration were recorded. As a result, the amount of the quench was proportional to the amount of the Ca
2+ influx. These results suggested that a cell, which has higher activity, accumulated larger amount of Mn
2+ in the neuron. Thus, our results supported that AIM-MRI can measure the history of the neuronal activities in the whole brain noninvasively in vivo.
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