THE MEASUREMENTS OF WHOLE-BRAIN NEURAL ACTIVITY AND MOTOR SKILLS AND EMOTIONAL BEHAVIOR IN DOPAMINE D1 RECEPTOR CONDITIONAL KNOCKDOWN MICE

In the striatum, projection neurons are divided into two groups: one is the direct pathway neurons expressing dopamine (DA) D1 receptors (D1R) and the other is the indirect pathway neurons expressing DA D2 receptors (D2R), which are known to be involved in motor initiation and termination, respectively. However, how DA modulates the activity of direct and indirect pathway neurons through D1R and D2R, and consequently influences whole-brain neural activity and motor function, remains unclear. To reveal the role of D1R, we conducted behavioral experiments and recorded the whole-brain neural activity in D1R conditional knockdown (D1RKD) mice, in which D1R expression can be controlled by doxycycline administration. The history of neural activity in the entire brain volume was measured using quantitative activation-induced manganese-enhanced MRI (qAIM-MRI). This measurement method uses Mn²⁺ as a surrogate marker for Ca²⁺. Mn²⁺ passes through voltage-dependent Ca²⁺ channels and is extruded very slowly from the cell. Mn²⁺ shortens the longitudinal relaxation time of H⁺ (T1), which is quantified by MRI so that R1 (=1/T1) is proportional to Mn²⁺ concentration. Therefore, qAIM-MRI can record the history of neural activity.
In behavioral experiments, significant motor impairment and increased anxiety were observed in D1RKD mice in which D1R expression was suppressed. The regions exhibiting significant elevation of neural activity were observed mainly in the limbic regions in D1RKD mice. These results suggested that the motor impairment observed in D1RKD mice during suppression of D1R expression might be associated with abnormalities in emotional function.