I. Introduction 1 1.1 Synapses are Important for Transmitting Information and Communication with Neurons. 1 1.2 Excitatory and Inhibitory Synaptic Proteins Are Associated with Neurotransmission. 2 1.3 Various Cb isoforms and Domains of Cb 3 1.3.1 SH3 Domain Has Autoinhibitory Roles by Adopting a Closed Conformation. 3 1.3.2 DH Domain Activates GTPases by functioning as specific GEF. 4 1.3.3 PH Domain Mediates Gephyrin Clustering by Binding with PI3P. 5 1.4 Missense Mutations of Collybistin Are Related with Neurodevelopmental Disorders. 5 II. Materials and Methods 8 2.1 Plasmids 8 2.2 Antibodies 8 2.3 Generation of Collybistin KO mice 9 2.4 Animals 9 2.5 Culture, Transfection, Immunostaining, and Imaging in COS-7 Cells 10 2.6 Culture, Infection, Transfection, Immunostaining, and Quantitative Analyses of Cortical and Hippocampal Neurons 11 2.7 Preparation of Brain Lysates and Immunoblot Analysis 11 2.8 Preparation of Lentiviruses 12 2.9 Preparation of Adeno-associated Viruses and Titration 12 2.10 Stereotaxic Injection 13 2.11 Mouse Behavioral Tests 13 Open-Field Test 14 Marble Burying Test 14 Elevated Plus Maze Test 14 Three-Chamber Sociability Test 15 Prepulse Inhibition 15 Ultrasonic Vocalization Test 16 2.12 Statistics 16 III. Results 17 3.1 Cb Isoforms Are Identified by Alternative Splicing of Cb mRNAs Depending on Its Species. 17 3.2 Collybistin Missense Variants Which Are Associated with Neurodevelopmental Disorders Express at the Same Level in Western Blotting. 17 3.3 CbII(SH3-) Mutation Transfected with EGFP-Gephyrin Showed Distinct Gephyrin Clustering Patterns Compared with CbII(SH3-) WT. 18 3.4 hCbIII Transfected With EGFP-Gephyrin and Neuroligin-2 (NL2) in COS-7 Cell Showed Various Gephyrin Cluster Forms Depending on Its Mutations. 19 3.5 Inhibitory Somatic Puncta Density Increased in Hippocampal Cultured Neurons Transfected with CbII(SH3-) WT. 20 3.6 CbII(SH3-) Missense Variants Transfected in Transfected Mouse Cultured Neurons to Identify the Function of Cb Domains. 20 3.7 Cb KO mice in the mPFC region Showed Behavioral Phenotypes in Behavioral Assays. 21 IV. Discussion and Conclusion 24 Figures 27 References 43 요약문 49