ИСТИНА

Excessive synchronization of local field potential activity (LFP) in the 15-30 Hz frequency range in the basal ganglia (BG) of Parkinson's disease (PD) patients, and in rodent models of PD is thought to contribute to motor dysfunction in PD. The mechanisms underlying the abnormal LFP patterns are not fully understood. Although exaggerated oscillations have been observed in several BG nuclei in PD, it is still unclear whether it manifests in the external globus pallidus (GPe), as the key nucleus of the BG network. The GPe has extensive reciprocal connections with the motor areas of the neocortex and all the nuclei of the BG [Saunders et al., 2015; Abecassis et al., 2019]. Due to its central location, it can make a significant contribution to oscillatory activity in the motor neural networks controlling locomotion. AIMs • Determine the role of GPe in generation and transmission of LFP oscillations throughout the motor circuits in rat model of PD. • Gain insight into the potential role of the GPe in supporting of PD motor symptoms (both movement impairment and Levodopa-induced Dyskinesia). CONCLUSIONS ▪ Loss of DA in PD rats leads to motor dysfunction which is companied by excessive coherent oscillations in two distinct motor circuits: (a) PFC-striato-pallidal with predominant 50-56 Hz mid-gamma oscillations, and (b) MCx-BG-VM thalamus with persistent 30-35 Hz beta oscillations. ▪ Increase in 50-56 Hz gamma activity in PFC-BG circuit coincides with occurrence of 30-35 Hz beta oscillations in MCx-BG circuit, and both are reduced by levodopa/APO. ▪ The emergence of beta and gamma LFP oscillations in hemispheres with DA-deficit suggests cooperative impact of motor circuits on support and execution of locomotion. ▪ The GPe is a critical component of the BG in controlling aberrant neurocircuit oscillations and motor dysfunction in PD. Its abnormal activity in PD rats may contribute to motor dysfunction. ▪ Alteration of GPe activity with Glu- and GABA-antagonists, as well as its inhibition by muscimol, reduces coherent oscillations and restores normal locomotion. ▪ The GPe is a critical site of the BG network in controlling the severity of LID. Inhibition of GPe activity by muscimol instantly eliminates levodopa-induced increases in 80-90 Hz high gamma thalamocortical activity and reduces dyskinesia.