Orexin receptors mediate long-term depression of excitatory synaptic transmission in the spinal cord dorsal horn
Orexin receptors mediate long-term depression of excitatory synaptic transmission in the spinal cord dorsal horn
- 주제(키워드) orexins , long-term synaptic depression , receptors , N-Methyl-D-Aspartate
- 발행기관 아주대학교
- 지도교수 문봉기
- 발행년도 2019
- 학위수여년월 2019. 2
- 학위명 박사
- 학과 및 전공 일반대학원 의학과
- 실제URI http://www.dcollection.net/handler/ajou/000000028391
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Neuropeptides orexin-A and -B are related to the regulation of sleep/wakefulness and feeding behaviors. Recently, the peptides have also been shown to yield antinociceptive effects in various pain models. However, it is not clear whether orexins are involved in forms of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), the increase and the decrease of synaptic efficacy, respectively. In the present study, we examined whether orexin receptor type 1 (OX1) and 2 (OX2) are involved in the induction or maintenance of LTD of excitatory synaptic transmission using transverse spinal cord slices of young rats. Repetitive electrical stimulation of Lissauer’s tract zone at 2 Hz for 5 min (600 pulses), combined with a holding potential of -30 mV, induced LTD of the amplitude of excitatory postsynaptic currents (EPSCs) which are evoked by the activation of primary afferent fibers. The maintenance of LTD was significantly prevented by bath application of SB674042 (1uM), an OX1 antagonist, or EMPA (1uM), an OX2 antagonist. In addition, LTD was dependent on the NMDA receptor, as the NMDA receptor antagonist D-AP5 blocked the maintenance of LTD. Our study suggests that orexins, via activation of both OX1 and OX2, play a significant role in the expression of NMDA-dependent LTD, thereby contributing to the spinal modulation of pain transmission.
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TABLE OF CONTENTS
Abstract ……………………………………………………………………ⅰ
Table of Contents…………………………………………………………ⅱ
List of Figures………………………………………………………………ⅲ
Ⅰ. Introduction…………………………………………………………….1
Ⅱ. Methods………………………………………………………………….3
1. Slice preparation…………………………………………………….3
2. Blind whole-cell patch clamp recordings…………………………….3
3. Drugs and data analysis……………………………………………….4
Ⅲ. Results………………………………………………………………….5
1. Low-frequency stimulation-induced LTD in the spinal cord substantia gelatinosa is dependent on postsynaptic depolarization………………5
2. OX1 and OX2 receptors mediate LTD……………………………….8
3. LFS-induced LTD is dependent on the NMDA receptor ………….13
Ⅳ. Discussion…………………………………………………………….14
Ⅴ. Conclusion…………………………………………………………….18
Ⅵ. Reference……………………………………………………………….19
Abstract (In Korean) ……………………………………………………….23
