Title Information
Title
Optogenetics-based Neuromodulation of the Cortico-Basal-Ganglia Circuitry in a hemi-Parkinsonian Rat Model
Name: Personal
Name Part
Yu, Zeyang
Role
Role Term: Text
creator
Name: Personal
Name Part
Nurmikko, Arto
Role
Role Term: Text
Advisor
Name: Personal
Name Part
Asaad, Wael
Role
Role Term: Text
Reader
Name: Personal
Name Part
Borton, David
Role
Role Term: Text
Reader
Name: Personal
Name Part
Hoffman-Kim, Diane
Role
Role Term: Text
Reader
Name: Personal
Name Part
Ozden, Ilker
Role
Role Term: Text
Reader
Name: Corporate
Name Part
Brown University. Biology and Medicine: Biomedical Engineering
Role
Role Term: Text
sponsor
Origin Information
Copyright Date
2019
Physical Description
Extent
xx, 220 p.
digitalOrigin
born digital
Note: thesis
Thesis (Ph. D.)--Brown University, 2019
Genre (aat)
theses
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.
Subject (fast) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01027584")
Topic
Motor cortex
Subject (fast) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01909981")
Topic
Optogenetics
Subject (fast) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01053693")
Topic
Parkinson's disease
Subject
Topic
Deep Brain Stimulation
Subject
Topic
Globus pallidus externus
Subject
Topic
Subthalamic nucleus
Subject
Topic
6-OHDA Rat Model
Subject
Topic
Beta oscillations
Language
Language Term (ISO639-2B)
English
Record Information
Record Content Source (marcorg)
RPB
Record Creation Date (encoding="iso8601")
20190603
Identifier: DOI
10.26300/yt0j-sf75
Access Condition: rights statement (href="http://rightsstatements.org/vocab/InC/1.0/")
In Copyright
Access Condition: restriction on access
Collection is open for research.
Type of Resource (primo)
dissertations