Title Page
ABSTRACT
Contents
1. INTRODUCTION 9
1.1. Background 9
1.1.1. Sensory processing and socio-affective recognition in autism 9
1.1.2. Neuronal growth regulator 1 as an autism-relevant molecule 11
1.1.3. Olfactory neurogenesis and social behavior 13
1.2. Purpose of Research 14
2. BODY 15
2.1. Methods 15
2.1.1. Animals 15
2.1.2. Behavioral tests 15
2.1.3. Bromodeoxyuridine (BrdU) incorporation assay 19
2.1.4. Immunohistochemistry (IHC) 20
2.1.5. Image analysis 20
2.1.6. Whole-cell voltage-clamp 21
2.1.7. K-means clustering 22
2.1.8. Statistics 22
2.2. Results 23
2.2.1. Negr1-/- mice are impaired in affective discrimination for stress and pain[이미지참조] 23
2.2.2. Dysregulated olfactory function of Negr1-/- mouse.[이미지참조] 29
2.2.3. Inhibitory inputs in the mitral cells of Negr1-/- mouse were increased along with their decreased excitability[이미지참조] 37
2.2.4. The number of neural progenitor cells are reduced in Negr1-/- mouse.[이미지참조] 39
3. CONCLUSION 43
3.1. Summary 43
3.2. Implication 44
3.3. Limitation and Future Research 46
3.4. Concluding Remarks 47
BIBLIOGRAPHY 48
국문초록 61
Figure 1. The Structure of NEGR1. 12
Figure 2. The pathway between the subventricular zone and the olfactory bulb in the brains of the adult mouse, the neonatal and adult human. 13
Figure 3. Negr1-/- mice are impaired in affective discrimination for stress.[이미지참조] 24
Figure 4. Negr1-/- mice are impaired in affective discrimination for pain.[이미지참조] 25
Figure 5. Sciatic nerve transaction induces neuropathic pain. 26
Figure 6. Negr1-/- mice are partially impaired in social novelty, but not sociability.[이미지참조] 28
Figure 7. Negr1-/- mouse socially interacts with conspecifics via olfaction.[이미지참조] 30
Figure 8. Negr1-/- mouse shows aberrant olfactory habituation and dishabituation for social odors.[이미지참조] 31
Figure 9. Negr1-/- mouse normally detects non-social odor.[이미지참조] 33
Figure 10. Negr1-/- mouse failed to associate a novel odor with reward.[이미지참조] 34
Figure 11. Negr1-/- mice are clustered distinctly from WT mice with olfactory(dis)habituation and affective discrimination.[이미지참조] 36
Figure 12. Inhibitory inputs are increased in the mitral cells of Negr1-/- mouse with a decrease in their excitability.[이미지참조] 38
Figure 13. The number of pSVZ NPCs is reduced in Negr1-/- mouse.[이미지참조] 40
Figure 14. The number of newly generated inhibitory neurons is reduced in the GL of Negr1-/- mouse.[이미지참조] 41
Figure 15. The number of newly generated cells is reduced in the GL of Negr1-/- mouse.[이미지참조] 42
Figure 16. Graphical summary. 43