Description
- Abstract:
- Deep brain stimulation (DBS) is an effective treatment for the mid/late stage Parkinson’s disease (PD), which significantly reduces the dopamine medication and improves motor symptoms. However, it does not offer a complete relief and some symptoms typically persist. A better understanding of its mechanism of action, further improvement in efficacy, and the identification of new therapeutic targets could benefit from pathway- and cell-type specific modulation methods. This dissertation focuses on utilizing optogenetic neuromodulation to interrogate the therapeutic effects of modulating multiple brain nuclei and fiber pathways within the cortico-basal-ganglia circuitry. In this thesis, I first developed methodological approaches for the functional opsin expression in the subthalamic nucleus (STN), globus pallidus externus (GPe), and motor cortex of non-transgenic rats. I then systematically evaluated the efficacies of various modulation paradigms on the alleviation of the characteristic symptom of rotational bias in a 6-OHDA hemi-Parkinsonian rat model, based on three main hypothesis: the inhibition of STN, the excitation of GPe, and the excitation of motor cortex. I found therapeutic improvements in rotational behavior, with individual differences, yielded from all of these optogenetic modulations. I also performed microelectrode array recording from the motor cortices of hemi-Parkinsonian rats to characterize the features of motor cortical beta-band oscillatory activities as biomarkers for the underlying Parkinsonism. I found the pathologically elevated beta band oscillations contained variations in spatial distribution, fluctuations in temporal dynamics, and instability in the frequencies. Additionally, I also showed that the phase synchrony of beta oscillations was enhanced across different motor cortical sites, which may serve as a complementary biomarker to the power-based measures. Overall, my work provided new considerations towards a closed-loop, adaptive neuromodulation paradigm for the treatment of Parkinson’s disease, utilizing optogenetics for pathway specific modulations and motor cortical pathophysiological biomarkers for feedback.
- Notes:
- Thesis (Ph. D.)--Brown University, 2019
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Citation
Yu, Zeyang,
"Optogenetics-based Neuromodulation of the Cortico-Basal-Ganglia Circuitry in a hemi-Parkinsonian Rat Model"
(2019).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.26300/yt0j-sf75
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Biomedical Engineering Theses and Dissertations
Theses and Dissertations for the Biomedical Engineering department....