Orexin receptors mediate long-term depression of excitatory synaptic transmission in the spinal cord dorsal horn

Alternative Title
Park Kibeom
Author(s)
박기범
Alternative Author(s)
Park Kibeom
Advisor
문봉기
Department
일반대학원 의학과
Publisher
The Graduate School, Ajou University
Publication Year
2019-02
Language
eng
Alternative Abstract
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.
URI
https://dspace.ajou.ac.kr/handle/2018.oak/15203
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Graduate School of Ajou University > Department of Medicine > 4. Theses(Ph.D)
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