Title

Dissecting Motivation: Circuit-Specific Molecular Mechanisms Underlying Social Engagement and Stress-Induced Passive Coping

Alternative Title

동기 행동의 분자적 해부: 사회적 보상과 스트레스 유도 수동적 대처의 회로 특이적 기전 연구

DGIST Authors

Tae-Eun Kim ; Hyosang Lee ; Ja Wook Koo

Advisor

이효상

Co-Advisor(s)

Ja Wook Koo

Issued Date

2026

Awarded Date

2026-08-01

Type

Thesis

Description

Chronic stress, Social motivation, Passive coping, VTA–NAc dopamine circuit, BLA–vHPC circuit

Table Of Contents

Ⅰ. Background 1
1.1 Motivation as a Multidimensional Construct 1
1.2 Chronic Stress as a Disruptor of Motivated Behavior 3
1.3 Neural Circuits Governing Motivated Behavior 6
1.3.1 The VTA–NAc Mesolimbic Dopamine Circuit for Approach Motivation and Social Reward 6
1.3.2 The BLA–vHPC Circuit for Stress Coping and Passive Behavioral Strategies 8
1.4 Molecular Mechanisms Linking Stress to Motivational Dysfunction 10
1.4.1 mGluR5-CREB-BDNF Signaling in the vHPC as a Molecular Basis of Passive Coping 10
1.4.2 Histone Dopaminylation and OCT3 in the NAc as an Epigenetic Basis of Social Motivation 12
1.5 Rationale and Research Objectives 15

Ⅱ. Positive Motivation for Social Engagement 19
2.1 Introduction 19
2.2 Materials and Methods 22
2.2.1 Experimental Animal 22
2.2.2 Effort-based Social Decision-Making （ESDM） Task 22
2.2.3 Stereotaxic Surgeries 25
2.2.4 Microinfusion and Pharmacology 27
2.2.5 Optogenetic Manipulation 28
2.2.6 Dopamine Fiber Photometry 29
2.2.7 AAV Production 30
2.2.8 Histology and Image Acquisition 32
2.2.9 RNA Extraction and RT-qPCR 32
2.2.10 Chromatin Immunoprecipitation （ChIP）-PCR 33
2.2.11 Fiber Photometry Analysis 34
2.2.12 Statistical Analysis 35
2.3 Results 37
2.3.1 NAc Dopamine D1 Receptor Mediates Social Motivation in Male Mice 37
2.3.2 NAc Dopamine Response Is Reinforced During the Mature Phase of Social Motivation 47
2.3.3 VTA–NAc Dopaminergic Circuit Modulates Social Motivation 57
2.3.4 Dopamine Itself Gives Positive Feedback to Social Motivation 67
2.4 Discussion 78

Ⅲ. Defensive Motivation in Stress Coping 87
3.1 Introduction 87
3.2 Materials and Methods 91
3.2.1 Experimental Animals 91
3.2.2 Chronic Social Defeat Stress （CSDS） 91
3.2.3 Subthreshold Social Defeat Stress （SSDS） 92
3.2.4 Social Interaction Test （SIT） 92
3.2.5 Forced Swim Test （FST） 92
3.2.6 Stereotaxic Surgeries 93
3.2.7 Cannula Implantation and Infusions 94
3.2.8 Optogenetic Manipulation 95
3.2.9 Histology and Image Acquisition 96
3.2.10 Quantitative Chromatin Immunoprecipitation 97
3.2.11 Western Blot 98
3.2.12 Statistical Analysis 99
3.3 Results 102
3.3.1 mGluR5 in BLA-recipient Circuits Regulates Stress-induced Social Avoidance and Coping Strategies 102
3.3.2 BLA-vHPC Circuit Exerts a Stronger Influence on Stress Coping than the BLA–mPFC Circuit 116
3.3.3 mPFC and vHPC Engage Distinct Molecular Mechanisms in Stress-induced Behaviors 123
3.3.4 Bdnf Transcription in the mPFC Is Unaffected by CSDS 128
3.3.5 CSDS Alters Bdnf Transcription in the vHPC 134
3.4 Discussion 141

Ⅳ. Conclusion 146

Ⅴ. References 150

Abstract in Korean 160

URI

https://scholar.dgist.ac.kr/handle/20.500.11750/60713
http://dgist.dcollection.net/common/orgView/200001006822

DOI

10.22677/THESIS.200001006822

Degree

Doctor

Department

Department of Brain Sciences

Publisher

DGIST

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