This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The striatal GABAergic output pathway will be labelled by activity-induced manganese-dependent contrast (AIM) MRI in the dopamine transporter knockout mice as compared to their wild type littermates. Activity-induced manganese-dependent contrast (AIM) MRI is a hemodynamic-independent functional MRI method that used manganese ion as an MR-detectable contrast agent. In this case, MnCl2 will be injected directly into the striatum. Upon functional stimulation of the brain, Mn2+ will accumulates in the active region(s) by entering active cells through voltage-gated Ca2+ channels, causing local signal increases in T1-weighted images. This relatively new method will allow us to follow the neuronal connection between the striatum and the subtantia nigra or the striatum and the globus pallidus. Therefore, since the activity of the striatal GABAergic neurons are tremendously increase in the dopamine transporter knockout mice, we expect that the accumulation of Mn2+ will be faster and stronger in the striatal target regions of these mice. Moreover, one pathway could be more activated than the other. These results would confirm and extend our previous biochemical data on the dopamine transporter mice as they would demonstrate indirectly the GABAergic neuronal activity. This work will have significant implications in a better understanding of the role of dopamine in hyperkinetic disorders.
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