Local field potential (LFP) power and phase-amplitude coupling (PAC) changes in the striatum and motor cortex reflect neural mechanisms associated with bradykinesia and rigidity during D2R suppression in an animal model

Impairments in motor control are the primary feature of Parkinson's disease, which is caused by dopaminergic imbalance in the basal ganglia. Identification of neural biomarkers of dopamine D2 receptor (D2R) suppression would be useful for monitoring the progress of neuropathologies and effects of treatment. Male Swiss albino ICR mice were deeply anesthetized, and electrodes were implanted in the striatum and motor cortex to record local field potential (LFP). Haloperidol (HAL), a D2R antagonist, was administered to induce decreased D2R activity. Following HAL treatment, the mice showed significantly decreased movement velocity in open field test, increased latency to descend in a bar test, and decreased latency to fall in a rotarod test. LFP signals during HAL-induced immobility (open field test) and catalepsy (bar test) were analyzed. Striatal low-gamma (30.3–44.9 Hz) power decreased during immobility periods, but during catalepsy, delta power (1–4 Hz) increased, beta1(13.6–18 Hz) and low-gamma powers decreased, and high-gamma (60.5–95.7 Hz) power increased. Striatal delta–high-gamma phase–amplitude coupling (PAC) was significantly increased during catalepsy but not immobility. In the motor cortex, during HAL-induced immobility, beta1 power significantly increased and low-gamma power decreased, but during HAL-induced catalepsy, low-gamma and beta1 powers decreased and high-gamma power increased. Delta–high-gamma PAC in the motor cortex significantly increased during catalepsy but not during immobility. Altogether, the present study demonstrated changes in delta, beta1 and gamma powers and delta–high-gamma PAC in the striatum and motor cortex in association with D2R suppression. In particular, delta power in the striatum and delta–high-gamma PAC in the striatum and motor cortex appear to represent biomarkers of neural mechanisms associated with bradykinesia and rigidity.