Investigation on synaptic functions of leucine- rich repeat domain-containing adhesion molecules LRRTMs and Slitrks at hippocampal neural circuits
- Title
- Investigation on synaptic functions of leucine- rich repeat domain-containing adhesion molecules LRRTMs and Slitrks at hippocampal neural circuits
- Author(s)
- Jinhu Kim
- Advisor
- 고재원
- Co-Advisor(s)
- Ji Won Um
- Issued Date
- 2024
- Awarded Date
- 2024-02-01
- Type
- Thesis
- Description
- LRRTMs;Slitrks;시냅스;해마;신경회로
- Table Of Contents
-
Introduction 1
1.1 Synapse & Synaptic adhesion molecules 1
1.2 Leucine-rich repeat-containing proteins 7
1.3 LRRTMs: extracellular binding family members for Neurexins 10
1.4 Slitrks: isoform-specific synaptic organizers at excitatory synapse and inhibitory synapse 12
1.5 Non-canonical functions of synaptic adhesion molecules 17
Materials and methods
2.1 Materials 20
2.1.1 Animals 20
2.1.2 Chemicals and Drugs 20
2.1.3 Recombinant DNA 21
2.1.4 Software 21
2.2 Methods 21
2.2.1 Electrophysiology 21
2.2.2 Expression vectors 24
2.2.3 Adeno-associated virus preparation 25
2.2.4 Virus titration 26
2.2.5 Statistical analysis 26
Results 27
3.1 LRRTM3 regulates the development of excitatory synapses at MEC-DG-CA3 synapses 27
3.1.1 LRRTM3 specifically regulates the development of excitatory synapses at MPP synapses. 27
3.1.2 LRRTM3 deficiency impairs long-term synaptic plasticity at Mf-CA3 synapses. 28
3.1.3 LRRTM3 regulates MEC-DG-CA3 synaptic homeostasis. 35
3.2 LRRTM4 regulates the development of excitatory synapses at LEC-DG synapses 42
3.2.1 LRRTM4 regulates spontaneous release at PP synapses. 42
3.2.2 LRRTM4 specifically regulates NMDAR-dependent EPSCs at LPP synapses. 46
3.2.3 LRRTM4 is not required for maintaining long-term synaptic plasticity at LPP synapses. 46
3.3 LRRTM2 is not required for regulating excitatory synaptic transmission in the DG 51
3.4 Synaptic functions of Slitrk1 and Slitrk2 in the hippocampal CA1 pyramidal neurons 55
3.4.1 Slitrk1 deficiency enhances spontaneous synaptic transmission and Slitrk2 deficiency reduces spontaneous synaptic transmission in CA1 pyramidal neurons. 55
3.4.2 Slitrk1 deficiency increases NMDAR-dependent eEPSCs at TA synapses, and Slitrk2 deficiency decreases both AMPAR-dependent eEPSCs and NMDAR-dependent eEPSCs at SC synapses. 59
3.4.3 Slitrk1 does not regulate asynchronous synaptic transmission at both SC and TA synapses, while Slitrk2 is crucial for regulating asynchronous synaptic transmission at SC synapses but not at TA synapses. 64
3.5 Synaptic functions of Slitrk1 and Slitrk2 in hippocampal DG granule neurons 69
3.5.1 Slitrk1 cKO or Slitrk2 cKO in the DG does not affect spontaneous synaptic transmission in DG granule neurons. 69
3.5.2 Slitrk2 regulates synchronous synaptic transmission at both MPP and LPP synapses, while Slitrk1 does not regulate synchronous synaptic transmission in DG granule neurons. 69
3.5.3 Slitrk1 regulates asynchronous synaptic transmission at MPP and LPP synapses, while Slitrk 2does not regulate asynchronous synaptic transmission at both PP synapses. 70
3.6 Significance of interactions with LAR-RPTPs for non-canonical synaptic functions of Slitrk 1 and Slitrk2. 82
3.6.1 LAR-RPTPs are indispensable binding partners of Slitrk2 for the regulation of synchronous synaptic transmission at SC synapses. 82
Discussion 85
References 90
- URI
-
http://hdl.handle.net/20.500.11750/47999
http://dgist.dcollection.net/common/orgView/200000723643
- Degree
- Doctor
- Department
- Department of Brain Sciences
- Publisher
- DGIST
- Related Researcher
-
-
Ko, Jaewon
- Research Interests Synapse Formation and Function; Neural Circuits; 뇌질환; animal model
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- Appears in Collections:
- Department of Brain Sciences Theses Ph.D.
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