Abnormal Functional Connectivity Of Theta Oscillations In The Dorsolateral Striatum And Substantia Nigra Pars Reticulata In L-DOPA-induced Dyskinesia Rats

OBJECTIVE:Levodopa induced dyskinesia(LID)is a common disabled drug complication in the patients with advanced Parkinson disease(PD).Currently,however,the mechanism of LID still not fully clarified.In recent years,Local field potential(LFP)electrophysiological recording technology,has been increasingly applied to neurophysiological brain networks including Parkinson's disease and other motor dysfunction disorders.At present,the dorsolateral striatum(dStr)and substantia nigra pars reticulate(SNr)brain network oscillations are still lack of related research.METHODS:Thirty-four rats were randomly assigned to receive a unilateral 6-OHDA lesion(n=18)or sham lesion with saline vehicle(n= 16),and each group then receive L-DOPA or saline intraperitoneally for 21 days.The rats were divided into 4 groups:6-OHDA + L-DOPA group,n = 9;6-OHDA + saline group,n = 9;Sham + L-DOPA group n = 8;Sham + saline group,n = 8.The dynamic spectral density,coherence and Granger causality analysis were analyzed for the dStr and SNr local field potentials within 4 hours of each of the four groups of rats,And further study of LID behavior and above electrophysiological changes by intraperitoneal injection of 5-HT autoreceptor agonist,eltoprazine.RESULTS:Compared with the sham + L-DOPA group,the dStr and SNr5-8Hz power spectral densities of the 6-OHDA + L-DOPA group were significantly enhanced,and the 5-8Hz coherence coefficient was significantly enhanced.Compared with the sham + Saline group,6-ODHA + saline group 24-36Hz power spectral density band was significantly increased,and this two regions 24-36Hz coherence significantly increased.In 6-OHDA + L-DOPA group,enhanced 5-8Hz oscillatory electrical activity of dStr and SNr was positively correlated within AIMs scores after playing the drug in3 hours.However,no correlation was found between these oscillations and AIMs scores during 1-21 days L-DOPA injection.In 6-OHDA +L-DOPA group,SNr to dStr 5-8Hz Granger causality was significantly higher than sham + L-DOPA group;in 6-ODHA + saline group,dStr to SNr 24-36Hz Granger causality coefficient was significantly higher compared with sham + saline group.Intraperitoneal injection of 5-HT1A/1B receptors agonists,eltoprazine,significantly reduced AIMs score,power spectral density,coherence coefficient,and Granger causality coefficient in 6-OHDA + L-DOPA group.CONCLUSIONS:The oscillatory activity in the SNR and dStr ? bands(5-8 Hz)of the LID rats is enhanced,and the two regions'? oscillations are coherent.This increased frequency of ?-band oscillatory activity was positively correlated with the AIMs score in different time point after L-DOPA injection.The direction of information flow for ? oscillations among this two structures was SNr? dStr in LID,but was dStr? SNr in PD.5-HT self-agonist etzolizine reduced the behavioral score of LID rats while reducing the oscillatory electrical activity in the enhanced 5-8 Hz band,and the direction of information flow between SNr and dStr in the ? oscillating activity also decreased.It is suggested that the 5-HT system not only participates in the physiological mechanism of LID,but also may improve the LID involuntary movement by adjusting the 0 oscillatory activity of the basal ganglia.