Title

Astrocytic phagocytosis-mediated synapse elimination maintains circuit homeostasis and plasticity in the adult brain

Alternative Title

성상교세포 매개 식균작용을 통한 성체 뇌의 회로 항상성과 가소성 유지

DGIST Authors

Ji-young Kim ; Han Kyoung Choe ; Hyungju Park

Advisor

최한경

Co-Advisor(s)

Hyungju Park

Issued Date

2022

Awarded Date

2022/08

Citation

Ji-young Kim. (2022). Astrocytic phagocytosis-mediated synapse elimination maintains circuit homeostasis and plasticity in the adult brain. doi: 10.22677/thesis.200000629582

Type

Thesis

Subject

Astrocytic phagocytosis, Synaptic plasticity, Learning and Memory, Hippocampus, Striatum

Description

Astrocytic phagocytosis, Synaptic plasticity, Learning and Memory, Hippocampus, Striatum

Abstract

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Table Of Contents

Ⅰ. INTRODUCTION 1
1.1 Introduction 1
1.1.1 Spine remodeling at different stages of an animal life 1
1.1.2 Functional roles of synapse formation and elimination during learning and memory 2
1.2 Multiple memory systems in the brain 2
1.3 Glial contribution to spine dynamics 3
1.4 Main questions of this study 5
Ⅱ. MATERIALS AND METHODS 6
2.1 Mice 6
2.2 AAV stereotaxic injection 6
2.3 4OHT and tamoxifen formulation 6
2.4 Immunohistochemistry 7
2.5 Confocal analysis 7
2.6 Tissue preparation using heavy metal staining protocol 8
2.7 Analysis of synaptic density and total vesicles using ssTEM 8
2.8 Imaging astrocytes for serial block-face scanning electron microscope (SBF-SEM) 8
2.9 Analysis of docked vesicles using conventional transmission electron microscope (Conventional TEM) 9
2.10 Whole-cell patch clamp 9
2.11 Extracellular field recording 11
2.12 Novel object recognition (NOR) and novel object location (NOL) test 12
2.13 Statistical analysis 12
Ⅲ. RESULTS 14
3.1 Astrocytic synapse phagocytosis is required for eliminating redundant synaptic connections 14
3.1.1 Astrocyte MEGF10 maintains the number of adult CA1 synapses 14
3.1.2 Astrocyte MEGF10 is essential for normal synaptic connectivity 14
3.2 Regulation of basal synaptic transmission in the hippocampus by astrocytic phagocytosis 15
3.2.1 Alterations of excitatory basal synaptic transmission by astrocytic MEGF10 KO 15
3.2.2 Postsynaptic functions and E/I balance are insensitive to astrocytic phagocytosis 15
3.3 Astrocytic phagocytosis is essential for normal presynaptic functions 16
3.3.1 Astrocytic phagocytosis regulates presynaptic release probability 16
3.3.2 Abnormal distribution of presynaptic vesicle pools in astrocytic MEGF10 KO 17
3.4 Astrocytic synapse elimination is required for normal hippocampal CA3 to CA1 synaptic plasticity and memory consolidation 18
3.4.1 Impaired synaptic plasticity at hippocampal CA3-CA1 with MEGF10 KO 18
3.4.2 Impaired hippocampal memory acquisition by astrocytic MEGF10 KO 19
3.5 Excitatory synapses in the striatum are regulated by astrocytic phagocytosis 19
3.5.1 Alteration of striatal excitatory synaptic connectivity and transmission by astrocyte MEGF10/MERTK KO 19
3.5.2 Corticostriatal excitatory inputs are selectively regulated by MEGF10; MERTK-mediated astrocytic phagocytosis 20
Ⅳ. DISCUSSION 22
4.1 Significance of astrocytic synapse elimination in the adult brain 22
4.2 Excitatory synapses as the main target of astrocytic synapse elimination 23
4.3 Essential role of constant synapse turnover in normal synaptic plasticity and learning and memory 24
4.4 Role of astrocytic phagocytosis in the adult striatal circuits 25
Ⅴ. REFERENCE 59

URI

http://dgist.dcollection.net/common/orgView/200000629582
http://hdl.handle.net/20.500.11750/16793

DOI

10.22677/thesis.200000629582

Degree

Doctor

Department

Department of Brain Sciences

Publisher

DGIST

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