Controlling the pathological activity of parkinsonian basal nuclei with the basal ganglia network model under light stimulation in the three-state, four-state channelrhodopsin, and three-state halorhodopsin optogenetic models

Autor: Nazlar Ghasemzadeh, Fereidoun Nowshiravan Rahatabad, Siamak Haghipour, Shabnam Andalibi Miandoab, Keivan Maghooli
Jazyk: perština
Rok vydání: 2024
Předmět:
Zdroj: مجله پزشکی دانشگاه علوم پزشکی تبریز, Vol 46, Iss 3, Pp 275-293 (2024)
Druh dokumentu: article
ISSN: 2783-2031
2783-204X
DOI: 10.34172/mj.2024.033
Popis: Background. Parkinson’s disease (PD) is a neurological disorder caused by the dysfunction of the basal nuclei, especially the substantia nigra, and a decrease in dopamine levels in the neural circuits of this part. In this paper, to investigate the effects of optogenetic stimulation on parkinsonian nervous systems, a complete model of basal ganglia (BG, including subthalamic nucleus [STN], globus pallidus interna [GPi], globus pallidus externa [GPe], and thalamus [TH] neurons) was first selected to simulate the neurons of the basal nuclei and was developed for PD using three- and four-state optogenetic stimulation. Methods. For this purpose, channelrhodopsin-2 (ChETA), ChRwt, and halorhodopsin (NpHR) opsins were evaluated in three-state and four-state stimulation modes, and different stimulation conditions according to different parameters in the BG model were taken into consideration. Results. To verify the developed model, the obtained results were compared with the results of experimental studies. The amount of compliance for different stimulation conditions and various genes underwent investigation. The value of the error index was calculated to evaluate the performance of the BG model for each gene in three- and four-state stimulation conditions with different values of basic parameters, and the stimulation conditions that created the error index equal to zero were introduced as optimal conditions. Based on the results, the frequencies of 20 Hz and 200 Hz in the four-state ChRwt model and the frequency of 80 Hz in the three-state ChETA model have been suggested as optimal genes, frequencies, and models. Conclusion. The response of GPe neurons was consistent with the experimental results, and the response of other neurons was also similar to the response of GPe neurons. In optimal conditions, STN and GPe neurons could provide excitatory input and appropriate inhibitory input to GPi, respectively, and GPi neurons could provide appropriate inhibitory input to TH, and as a result, its function improved and the pathological effects of PD disappeared. Practical Implications. In this research, it has been attempted to improve the function of the basal nuclei of the brain by using optogenetic stimulation and the elimination of the pathological symptoms of PD.
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