Effect Of Levodopa On Thalamicostriatal Pathway Electrophysiology In Rats With Parkinson’s Disease

Parkinson’s disease(PD)is a disorder dyskinesias in which the direct and indirect pathways of the cortex-basal ganglia-thalamus circuit are lost due to damage to dopamine(DA)neurons in the substantia nigra.However,there is more and more evidence that in addition to the two signal pathways described above,PD direct projection of the thalamus to the striatum also plays a pivotal role.Recent studies have confirmed that the thalamus has a large number of fiber projections into the striatum,mainly from the thalamus nucleus group,that is,the central thalamic nuclei/parafascicular nuclear complex(CM / PF)or rodent parathalamic Nuclear(parafascicular nucleus,PF).The role of the thalamicostriatal pathway in PD pathology has recently attracted much attention.Levodopa(L-DOPA)is an important drug in the history of Parkinson’s disease treatment.So far,most of the researches on its therapeutic effects have focused on the relevant pathways from the cortex to the basal ganglia and the interior of the basal ganglia.The basal ganglia-thalamus pathway,especially the thalamic striatum pathway,has been relatively few.In addition,the study found that the electrophysiological activities of neurons in PF have changed in PD patients and PD animal models under anesthesia,suggesting that the electrophysiological activities of PF neurons may be related to the behavioral state of PD.At present,some studies have found that the reduction of DA energy neurons leads to dysfunction of synaptic transmission of PF to the striatum,but no experimental study has investigated whether L-DOPA affects the changes in the correlation of oscillating activity between PF and the striatum.In view of this,this study focuses on the striatum(STR)and parafascicular complex(PF)in the thalamicostriatal pathway of rats after L-DOPA intervention in the rest and treadmill.In this study,the electroencephalogram signals of two nuclear group neurons in different states were recorded by implanting nickel-chromium alloy wire microelectrodes into PF and STR of rats in normal control group,6-OHDA injury group and L-DOPA drug intervention group.The experimental results are as follows:1.Analysis of PF and STR neuron typesIn this study,PF nuclei are divided into two subtypes,PF I and PF II,according to their electrophysiological characteristics.The striatum is divided into medium spiny neuron(MSN),cholinergic interneuron(CIN)and fast spiking inerneurons(FSI)according to their most obvious characteristics.2.L-DOPA changes PD discharge rate and discharge pattern of PF and STR neurons in PD rats,and plays a therapeutic role in PD.The discharge rate of the two types of PF neurons did not change significantly in the resting state of rats.The discharge of PF I neurons increased after PD,while PF II neurons showed a more regular trend.The L-DOPA drug intervention group changed the discharge pattern of PF I neurons.The striatum significantly increased the discharge rate of MSN in PD rats,and the discharge was more irregular,while the electrical activity of the other two types of neurons did not change significantly.The L-DOPA drug intervention group not only changed the discharge rate and discharge pattern of MSN but also the discharge mode of CIN was changed,that is,the possibility of explosive discharge was reduced,and the discharge was more regular3.L-DOPA changes the correlation value between the PF spike and its own field potential in PD rats,and thus has a therapeutic effect on PD.After PD,the synchronization between the release of PF spikes and the local field potential Beta(12-35 Hz)band oscillations increased significantly.The L-DOPA drug intervention group changed the mean linear correlation compared to the PD group,but the phase correlation did not change significantly.Among them,the PF I neuron only increased the Beta band correlation value in the stationary state after PD,and the PF II neuron only increased the correlation value in the0.7-12 Hz and 12-35 Hz frequency bands under the treadmill motion state,the L-DOPA drug intervention group reduced the pathological increase of correlation values in this frequency band.In the awake and resting state of rats,the Beta band synchronization of PF I neurons was enhanced after PD.The L-DOPA drug intervention group changed the average vector length value and the phase angle value did not change significantly.When the rats were on a treadmill,PF II neurons were more synchronized in the 12-35 Hz band after PD,and the L-DOPA drug intervention group changed the average vector length value,but also changed the phase angle of the 0.7-12 Hz band value.4.L-DOPA changes the correlation value between the PF spike and the striatum field potential in PD rats,and thus has a therapeutic effect on PD.The average linear correlation between spikes of PF I neurons and striatum LFP after PD increased in the Beta frequency band,and the average linear correlation of PF II neurons was 0.7-12 Hz frequency band decreased,but there was no significant change in the L-DOPA drug intervention group compared with the PD group.In the resting state,the average vector length of PF I neuron spike and striatum LFP increased in the Beta band,and the average vector length of PF II neuron decreased in the 0.7-12 Hz band.There was no significant change in the average phase angle of PF neurons,and there was no significant change in the L-DOPA drug intervention group compared with the PD group.In the treadmill state,only the average vector length of PF I neuron spike and striatum LFP increased in the Beta band,and L-DOPA drug intervention changed the pathological increase in the PD group,So as to play a therapeutic role in PD.In summary,L-DOPA changes the peak discharge rate and discharge pattern of PF and STR neurons in PD rats,and plays a therapeutic role;L-DOPA changes the correlation value of peak potentials and field potentials of PF neurons in PD rats.,Especially the linear correlation value,thus playing a therapeutic role.The correlation between PF spike and LFP after PD has different changes in different behavioral states and different types of neurons in rats,indicating that the changes in the neurophysiological activity of PF are significantly related to the behavioral state of rats.