Metabotropic glutamate receptor group 1의 새로운 결합 단백질인 Calsyntenin-3의 기능에 대한 연구
Table Of Contents
I. Introduction 1.1 Synapses play a role in information processing and transmission 1 1.2 Synaptic adhesion molecules (SAMs) orchestrate synapse development and function 3 1.3 Heterogeneous functions of Clstn protein family 4 1.3.1 Clstn1 is involved in excitatory synapses 5 1.3.2 Clstn2 knockout leads to reduced inhibitory synapses 6 1.3.3 Clstn3 regulates excitatory synaptic innervation 6 1.4 Glutamate receptors come in two main types: ionotropic (iGluR) and metabotropic (mGluR) 9 1.4.1 Molecular structure and functions of mGluRs 10 1.4.2 mGluR5 is related to LTP and LTD 12 1.4.3 mGluR5 is activated through dimerization 14 1.4.4 mGluR5 signaling pathway is involved in synaptic plasticity, memory, and cognition 14
II. Material and Methods 2.1 Animal 17 2.2 Cell-surface binding assays 18 2.3 Preparation of Adeno-Associated Viruses and Titration 18 2.4 Electrophysiology 19 2.5 Behavior test 23 2.6 Pharmacological rescue 24 2.7 Statistical analysis 24
III. Results 3.1 Deficiency of Clstn3 affects synaptic function in CaMKIIα-Clstn3 mice 26 3.1.1 Excitatory synaptic transmission is reduced in CA1 pyramidal neurons of CaMKIIα-Clstn3 mice 26 3.1.2 Evoked synaptic responses are reduced in CA1 pyramidal neurons of CaMKIIα-Clstn3 mice 28 3.1.3 Synaptic transmission of mPFC pyramidal neurons is not affected in CaMKIIα-Clstn3 mice 30 3.1.4 Both AMPAR and NMDAR-dependent EPSCs are not altered in mPFC of CamKIIα-Clstn3 mice 31 3.2 Clstn3 deficient affects synaptic function in CA1-specific Clstn3-cKO mice 32 3.2.1 Basal synaptic transmission is not affected CA1-specific Clstn3-cKO mice 32 3.2.2 AMPAR-mediated synaptic responses are enhanced in Clstn3-deleted CA1 pyramidal neurons 33 3.3 Social hierarchy is not altered in CA1-specific Clstn3-cKO mice 34 3.4 Clstn3 deficient affects synaptic function in mPFC-specific Clstn3-cKO mice 34 3.4.1 Excitatory synaptic transmission is increased in Clstn3-deleted mPFC pyramidal neurons 34 3.4.2 NMDAR-mediated synaptic responses are enhanced in Clstn3-deleted mPFC pyramidal neurons 36 3.5 Social hierarchy is reduced in mPFC-specific Clstn3-cKO mice 37 3.6 MTEP treatment reverses social hierarchy in mPFC-specific Clstn3-cKO mice 38