Title

Investigating the synaptic functions of Slitrk2 and Slitrk3 in the hippocampus and medial prefrontal cortex

Alternative Title

해마와 전전두엽에서 시냅스 기능을 조절하는 Slitrk2와 Slitrk3의 역할 조사

DGIST Authors

Dongwook Kim ; Ji Won Um ; Se-Young Choi

Advisor

엄지원

Co-Advisor(s)

Se-Young Choi

Issued Date

2024

Awarded Date

2024-08-01

Citation

Dongwook Kim. (2024). Investigating the synaptic functions of Slitrk2 and Slitrk3 in the hippocampus and medial prefrontal cortex. doi: 10.22677/THESIS.200000801803

Type

Thesis

Description

Slitrk2, Slitrk3, Excitatory synapse, Inhibitory synapse, Neurological disorder, interneurons

Table Of Contents

Ⅰ. INTRODUCTION
1.1 General introduction 1
1.2 Part 1. Introduction 1
1.3 Intellectual disability is caused by a malfunction of synaptic proteins 2
1.4 Slitrk proteins are associated with ID 4
1.5 ID is caused by dysfunctions of the mPFC and hippocampus 7
1.6 Interneurons act as mediators between neurons in the nervous system 8
1.7 Classification of interneurons 9
1.8 The roles of synaptic CAMs are cell-type dependent 10
1.9 Non-canonical function of synaptic CAMs 10

ⅠⅠ. MATERIALS AND METHODS
2.1 Method of part 1. 12
2.1.1 Generation of Slitrk2 conditional knockout (cKO) mice 12
2.1.2 Antibodies 12
2.1.3 Immunoblotting 13
2.1.4 Immunohistochemistry 13
2.1.5 AAV Production, Stereotactic Surgery, and Virus Injections.14
2.1.6 Behavioral Analyses 15
2.1.7 Data Analysis and Statistics16
2.2 Method of part 2. 16
2.2.1 Generation of Slitrk3 cKO mice 16
2.2.2 Expression Vectors 17
2.2.3 Antibodies 17
2.2.4 Immunoblotting 18
2.2.5 AAV Production, Stereotactic Surgery and Virus Injections 18
2.2.6 RNAscope Assay 19
2.2.7 Immunohistochemistry 20
2.2.8 Electrophysiology 20
2.2.9 Behavioral Tests 22
2.2.9 Data Analysis and Statistics 33

ⅠⅠⅠ. RESULTS
3.1 Part 1. Research on Slitrk2 24
3.1.1 Identification of Slitrk2 variants in patients with ID 24
3.1.2 Slitrk2 KO mice exhibit abnormal anxiety-like behavior, cognitive impairment,
memory deficits, and abnormal gaits 24
3.1.3 The behavioral abnormalities of Nestin-Slitrk2 mice reflect a reduction of excit-
atory synapses in the hippocampus 26
3.1.4 The Slitrk2 T312A mutant, found in human patients, was unable to rescue the
memory deficits of Slitrk2 KO mice 27
3.2 Part 2. Research of Slitrk3 43
3.2.1 Deletion of Slitrk3 in cortical cultured neurons results in a reduction of inhibitory
synapses 43
3.2.2 Slitrk3 specifically regulates inhibitory synapses in the mPFC 43
3.2.3 mPFC-specific knockout of Slitrk3 leads to abnormal anxiety-like behavior and
impaired fear memory 44
3.2.4 The Slitrk3 protein contributes to inhibiting synaptic transmission in the mPFC
45
3.2.5 Slitrk3 binds with ErbB1 and PTPδ to regulate inhibition from VIP-interneurons
to SST-interneurons 57
3.2.6 Slitrk3 protein regulates synaptic transmission in SST-positive interneurons
46

ⅠV. CONCLUSION & DISCUSSION 68
4.1 General conclusion & discussion 68
4.2 Conclusion & discussion in relation to results of part 1. 69
4.3 Conclusion & discussion in relation to results of part 2. 70

V. REFERENCES 72

URI

http://hdl.handle.net/20.500.11750/57563
http://dgist.dcollection.net/common/orgView/200000801803

DOI

10.22677/THESIS.200000801803

Degree

Doctor

Department

Department of Brain Sciences

Publisher

DGIST

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