Exercise Improves the Lateral Inhibition of D2MSN-D1MSN in the Striatum to Regulate Basal Ganglia Information Output in Parkinson’s Disease Mice

Objective: To investigate the role and mechanism of striatum D2MSN-D1MSN lateral inhibition in improving basal ganglia information output by observing the effects of exercise and dopamine type Ⅱ receptor(D2R) agonist intervention on the inhibition of striatum D2MSN-D1MSN in PD mice. Methods: D2-Cre mice were microinjected with Optogenetic viral(rAAV-Ef1α-DIO-ChR2-EYFP-WPRE-pA) into right striatum to optogenetic manipulate D2MSN, then the mice were randomly divided into a control group(D2-Cre) and a model group. The PD mice model was established by injecting neurotoxin 6-OHDA into the striatum with 6-Hydroxydopamine hydrobromide(6-OHDA) in two weeks, while the control group was injected saline at the same position.The PD mice were identified and then randomly divided into PD group(PD^D2-Cre) and PD exercise group(PD+Ex^D2-Cre). The constant speed treadmill exercise(18 m/min, 40 min/d, 5 d/w) for 4 weeks or D2R agonist was set as intervention method in each group. After intervention, striatum D2MSN-D1MSN lateral inhibition was examined by whole cell patch clamp combined with optogenetic technique. The D2R agonist was applied to examine whether the lateral inhibition change depends on D2R or not. Results: The number of D1-MSNs action potentials in the PD^D2-Cre group was significantly lower than the D2-Cre group(P<0.05); the PD+Ex^D2-Cre group was significantly higher than that of PD+Ex^D2-Cregroup and lower than D2-Cre group(P<0.05). Using D2R agonist drug characteristics to interfere with D2-MSNs, the ratio of oIPSC amplitude to baseline in D1-MSNs of PD^D2-Cregroup was significantly higher than the D2-Cre group(P<0.05), and PD+Ex^D2-Cregroup was significantly lower than PD^D2-Cregroup, but higher than the D2-Cre group(P<0.05); the maximal field inhibitory post synaptic potential(fIPSP)amplitude of SNr induced by optogeneticstimulate D2-MSN in PD^D2-Cregroup was significantly lower than the D2-Cre group(P<0.05). PD+Ex^D2-Cregroup was significantly higher than PD^D2-Cre group, but lower than the D2-Cre group(P<0.05). Conclusion: The abnormal lateral inhibition affects the information output of SNr in PD mice, which may be one of the important mechanism of PD basal ganglia dysfunction. Four-week exercise intervention adjusted the SNr information output by improving the D2MSN-D1MSN lateral inhibition in the striatum of PD mice,and D2R plays an important role in exercise-improved D2MSN-D1MSN lateral inhibition and the regulation of basal ganglia information output.