The Research On The ?oscillation In Motor Cortex-substantia Nigra Pars Reticulata Neural Pathway Of Levodopa-Induced-Dyskinesia Rats

OBJECTIVELevodopa-induced dyskinesia(LID)is a disabled drug complication in advanced Parkinson's disease(PD)clinically.So far,the electrophysiological mechanism related to LID has not been fully clarnfied.Thus,we simultaneously record the local field potentials(LFPs)in LID/PD rodent model among primary motor cortex(M1)and substantia nigra pars reticulata(SNr)in vivo while performing different drug intervention.In our study,we aim to investigate the electrophysiological mechanism of dyskinesia,and further clear the intrinsic electrophysiological properties in PD and LID rats.METHODSTwenty-seven male SD rats were divided into three groups randomly,including sham group(n=7),PD group(n=10),and LID group(n=10).LFP recording and analysis of M1 and SNr were performed before and after acute levodopa administration in three groups under awake,free moving state.AIMs during "on"stage and response time(?t)were also recorded.After that,chronic(13 days)drug intervention was further performed with 5-HTIA/B agonist(eltoprazine,Elto).At day 14,16,and 18 days,LFP were recorded before dopamine receptor agonist(levodopa in Day14,Qurinpirole in Day 16,and SKF 38393 in Day 18,respectively)and At,AIMs score were recorded during "on" stage,respectively.RESULTSCompared with the sham group before levodopa administration,enhanced oband(4-10Hz)power spectral density(PSD)and M1-SNr coherence were recorded and found in PD group and LID group after acute levodopa injection respectively,while enhanced Ooscillation and M1-SNr coherence were not different between PD group and LID group.Compared with PD group and sham group,enhanced 0 band frequency were found in the "off" stage in LID group,accompanied by significantly shortened At.On Day14,16,18,compared with PD/LID group,the ?t of AIMs wassignificantly shorter than that of PD/LID+Elto group after dopaminergic agonists'challenging,respectively,accompanied by the increased 0 coherence and "SNr?M1"information flowing during "off" stage.CONCLUSIONSIncreased M1-SNr functional connectivity during "on" stage is closely related to the emergence of AIMs but not related to its severity,and the direction of information flow in this period is SNr?M1.In LID,there exists information flow in SNr to M1 during "off" stage,and meanwhile,At of AIMs is significantly reduced in LID rats.SNr?M1 information flow may mediate sensitivity of dyskinesia.In experiment two,the above results were further proved,we also found that Elto could effectively block 0information flow from SNr to M1 during "off" stage.The application of D2 and D1 agonists further indicated that SNr?M1 information flow had no specificity in direct or indirect pathways.More importantly,such information flow in 0 band frequency could effectively mediate the sensitivity of AIMs induced by dopaminergic drugs.Our results also show that Elto may be involved in the pathophysiological mechanisms associated with LID,and may reverse or control the formation of maladaptive synaptic plasticity of dyskinesia and weaken the sensitivity to dopaminergic drugs by blocking the functional connection of SNr to M1.