Upon dopaminergic depletion, both patients with Parkinson’s disease (PD) and experimental animals show behavioral manifestations only with substantial neuronal loss (80~90%)1, 2. Identification and visualization of the adaptive plasticity for dopaminergic injuries remains lacking in the neuroscience literature, with both its location and neurochemical nature being most debated1, 3-10. Functional magnetic resonance imaging (fMRI) can be a useful tool to pinpoint the location and neurochemistry of changes in brain activity11. In this study, a pain-evoked cerebral blood volume (CBV)-weighted fMRI paradigm is used to investigate the crosstalk between the divergent glutamatergic and dopaminergic systems that converge on the striatum, to determine what currently remains unknown regarding the compensatory plasticity upon dopaminergic depletion.The rat PD animal model was induced by an intraperitoneal injection of desipramine (15 mg/kg) and then lesioning the right substantia nigra (SN) with 15 mg of 6-hydroxydopamine (6-OHDA) in a volume of 3 ml dissolved in ice-cold 0.02% ascorbic acid. The coordinates for the right SN pars compacta were 5.3 mm posterior, 2.1 mm lateral, and 8.2 mm ventral from the bregma. For measuring the motor deficits, the rats were injected intraperitoneally with methamphetamine (2 mg/kg), and then their rotation behavior was recorded and analyzed. A rat is considered to be parkinsonian when the rotation reaches 360 turns/h. For the day 1 group, the rats received either saline or MK801 via the tail vein at 15 minutes before the administration of methamphetamine. fMRI was conducted using a 4.7-T spectrometer (Biospec 47/40, Bruker, Germany) with a 72-mm-volume coil as the radiofrequency transmitter and a quadrature surface coil as the receiver. For each sensory stimulation evoked fMRI data set, a time series of 60 images were acquired in the axial plane. The first 12, second 12, third 12, fourth 12, and last 12 time frames correspond to the off, on, off, on, and off phases of nociceptive electrical stimulation, respectively, which was delivered to a left or right forepaw via a pair of needle electrodes. Gradient-echo images were acquired in the time series with a repetition time of 150 ms, an echo time of 15 ms, a flip angle of 22.5°, a field of view of 2.56 cm by 2.56 cm, a slice thickness of 1.5 mm, an acquisition matrix of 128×64 (zero-filled to 128×128), and a temporal resolution of 9.6 s. The stimulation intensity was 3 mA or 1 mA, administered by a constant-current stimulator (model 2100, A-M Systems, Carlsborg, WA, USA). The contrast agent was from MegaPro Biomedical Co. Ltd. fMRI correlation maps were generated by the Pearson correlation coefficient (CC) between the image signals and the off–on–off–on–off electrical stimulation paradigm on a voxel-by-voxel basis using the cross-correlation method 12. The cutoff point for the CC was r=±0.2513, 14. NMDAR and D1R antagonism were achieved by MK801 and SKF83566, respectively, injected intravenously during MRI 15 16. The designated administration time point was 5 minutes before the acquisition of a stimulation-evoked fMRI dataset (an off-on-off-on-off stimulation paradigm). After fMRI experiments, the rats were perfused for immunohistology using 4% paraformaldehyde, and the brains were cryosectioned at 50 mm and stained for tyrosine hydroxylase (TH).When the painful stimulation was applied to the left forepaw of the rats in the early stage after right intranigral 6-OHDA (15µg/Kg) injection, a remarkable novel vasodilation cluster was observed in the DOLS ipsilateral to the lesioned SN at day 1 post-lesion. The DOLS vasodilation is a major sign that marks the difference between the early and late stages of dopamine depletion. The DOLS vasodilation occurs in response to both high intensity (noxious) and low intensity (innoxious) electrical stimulation. Pharmacological testing indicates that the evoked DOLS vasodilation is caused primarily by NMDAR, and secondarily by D1R. When examining the dopaminergic fibers of these brain tissues, we found that the location of the residual dopaminergic fibers coincides with the region exhibiting vasodilation. Moreover, behavioral testing shows that NMDAR antagonism advanced the motor dysfunction of the day 1 rats to a level considered parkinsonism, suggesting that DOLSN activity produces effects compensating for the motor dysfunction in the early stage after dopaminergic depletion. For the first time, robust evidence is available that indicates an important mechanism to motor compensation upon dopaminergic loss being DOLSN-dependent mediation. In this, the sensory stimulus-evoked CBV-weighted fMRI technique plays an indispensable role in detecting the mechanism. fMRI reveals that DOLSN activity represents the crosstalk between the glutamatergic corticostriatal tracts and dopaminergic nigrostriatal fibers at the convergent synaptic site to cope with the endangered dopaminergic system.