Long-term depression of nociceptive synapses by non-nociceptive afferent activity: Role of endocannabinoids, Ca²⁺, and calcineurin

详细信息	查看全文 | 推荐本文 |

• 作者：Sharleen Yuan ^{sharleen.yuan@usd.edu} ; Brian D. Burrell ; ^{bburrell@usd.edu} ;
• 关键词：Heterosynaptic ; Endocannabinoids ; LTD ; Nociception ; Gate control ; Leech
• 刊名：Brain Research
• 出版年：2012
• 期刊代码：8_00068993
• 类别：neu
• 出版时间：15 June, 2012
• 卷：1460
• 期：Complete
• 页码：1-11
• 文件大小：727 K

摘要

Activity in non-nociceptive afferents is known to produce long-lasting decreases in nociceptive signaling, often referred to as gate control, but the cellular mechanisms mediating this form of neuroplasticity are poorly understood. In the leech, activation of non-nociceptive touch (T) mechanosensory neurons induces a heterosynaptic depression of nociceptive (N) synapses that is endocannabinoid-dependent. This heterosynaptic, endocannabinoid-dependent long-term depression (ecLTD) is observed where the T- and N-cells converge on a common postsynaptic target, in this case the motor neuron that innervates the longitudinal muscles (L-cells) that contributes to a defensive withdrawal reflex. Depression in the nociceptive synapse required both presynaptic and postsynaptic increases in intracellular Ca²⁺. Activation of the Ca²⁺-sensitive protein phosphatase calcineurin was also required, but only in the presynaptic neuron. Heterosynaptic ecLTD was unaffected by antagonists for NMDA or metabotropic glutamate receptors, but was blocked by the 5-HT₂ receptor antagonist ritanserin. Depression was also blocked by the CB1 receptor antagonist rimonabant, but this is thought to represent an effect on a TRPV-like receptor. This heterosynaptic, endocannabinoid-dependent modulation of nociceptive synapses represents a novel mechanism for regulating how injury-inducing or painful stimuli are transmitted to the rest of the central nervous system.