Title

Investigating the excitatory-inhibitory imbalance in Alzheimer's disease using cerebral cortex and ganglionic eminence fusion organoids

Alternative Title

대뇌 피질-신경절 융기 융합 오가노이드를 활용한 알츠하이머병에서의 흥분-억제 불균형 연구

DGIST Authors

Juran Choe ; Sung Bae Lee ; Jinsoo Seo

Advisor

이성배

Co-Advisor(s)

Jinsoo Seo

Issued Date

2025

Awarded Date

2025-08-01

Type

Thesis

Description

AD, Fusion brain organoids, E/I imbalance, Network hyperactivity, PV+ interneuron vulnerability

Table Of Contents

Ⅰ. Introduction 1
1.1 Genetic and pathological distinctions between sporadic and familial Alzheimer’s Disease 1
1.2 Limitations of traditional AD models and the need for mutation-specific approaches 1
1.3 Establishing human-relevant excitatory and inhibitory circuit models to probe early network dysfunction in AD 3
1.4 Uncovering the role of E/I imbalance and oscillatory deficits in AD through electrophysiological profiling 5
Ⅱ. Materials and Methods 8
2.1 iPSCs lines 8
2.2 Generation of Cx:GE fusion organoid 8
2.3 MEA recording 9
2.4 MEA analysis 10
2.5 Immunohistochemistry 11
2.6 ELISA 12
Ⅲ. Results 13
3.1 Establishing a Cx:GE fusion organoid model for studying E/I network changes in AD 13
3.2 Validation of regional patterning, interneuron migration, and synaptic integration in Cx:GE fusion organoids 17
3.3 Mutation-Specific Mechanisms Underlying Organoid Size Alterations 22
3.4 Region-specific MEA recording and pharmacological dissection of inhibitory and excitatory activity 26
3.5 Dissecting inhibitory tone, excitatory activity, and network activity across AD fusion organoids 29
3.6 Temporal and line-specific alterations in network synchrony in AD fusion organoids 35
3.7 Assessment of network oscillation changes in AD fusion organoids using interspike interval (ISI) coefficient of variation (CoV) 49
3.8 Analysis of theta and gamma rhythms derived from LFP recordings 43
3.9 Temporal progression of AD-related pathology in fusion organoids 48
3.10 Selective vulnerability of PV+ interneurons in AD fusion organoids 53
Ⅳ. Discussion 58
Ⅴ. References 65
Abstract in Korean 71

URI

https://scholar.dgist.ac.kr/handle/20.500.11750/59812
http://dgist.dcollection.net/common/orgView/200000888175

DOI

10.22677/THESIS.200000888175

Degree

Master

Department

Department of Brain Sciences

Publisher

DGIST

Show Full Item Record