Youn Dong-Ho, Royle Gordon, Kolaj Miloslav, Vissel Bryce, Randić Mirjana
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
Pain. 2008 May;136(1-2):158-67. doi: 10.1016/j.pain.2007.07.001. Epub 2007 Sep 10.
Ca(2+)-permeable-AMPA receptors (AMPARs) are expressed in the superficial dorsal horn (SDH, laminae I/II) of the spinal cord, the area involved in transmission and modulation of sensory information, including nociception. A possible role of Ca(2+)-permeable-AMPARs in synaptic strengthening has been suggested in postnatal DH cultures, but their role in the long-lasting activity-dependent synaptic plasticity of primary afferent neurotransmission in the adult mouse SDH has not been investigated. In the present study the role of Ca(2+)-permeable-AMPARs in the regulation of long-lasting synaptic plasticity, specifically long-term potentiation (LTP) and long-term depression (LTD) in the SDH, was investigated using mice deficient in AMPAR GluR2 subunit. We show here that the GluR2 mutants exhibited no changes in passive membrane properties, but a significant increase in rectification of excitatory postsynaptic currents, the finding suggesting increased expression of Ca(2+)-permeable-AMPARs. In the absence of GluR2, high-frequency stimulation (HFS) of small-diameter primary afferent fibers induced LTP that is enhanced and non-saturating in the SDH at both primary afferent Adelta- and/or C-fibers monosynaptic and polysynaptic pathways, whereas neuronal excitability and paired-pulse depression were normal. The LTP could be induced in the presence of the NMDA receptor antagonist d-AP5, and L-type Ca(2+) channel blockers, suggesting that Ca(2+)-permeable-AMPARs are sufficient to induce LTP in the SDH neurons of adult mouse spinal cord. In contrast, the induction of HFS-LTD is reduced in the SDH of GluR2 mutants. These results suggest an important role for AMPAR GluR2 subunit in regulating synaptic plasticity with potential relevance for long-lasting hypersensitivity in pathological states.
钙离子通透型α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPARs）表达于脊髓背角浅层（SDH，I/II层），该区域参与感觉信息（包括伤害性感受）的传递和调制。在出生后背角培养物中，已有人提出钙离子通透型AMPARs在突触增强中可能发挥作用，但它们在成年小鼠SDH初级传入神经传递的长期活动依赖性突触可塑性中的作用尚未得到研究。在本研究中，利用缺乏AMPAR GluR2亚基的小鼠，研究了钙离子通透型AMPARs在调节SDH中持久突触可塑性（特别是长时程增强（LTP）和长时程抑制（LTD））方面的作用。我们在此表明，GluR2突变体的被动膜特性没有变化，但兴奋性突触后电流的整流显著增加，这一发现表明钙离子通透型AMPARs的表达增加。在缺乏GluR2的情况下，对小直径初级传入纤维的高频刺激（HFS）在SDH中诱导出LTP，在初级传入Aδ-和/或C-纤维单突触和多突触通路中均增强且不饱和，而神经元兴奋性和双脉冲抑制正常。LTP可在NMDA受体拮抗剂d-AP5和L型钙离子通道阻滞剂存在的情况下诱导产生，这表明钙离子通透型AMPARs足以在成年小鼠脊髓SDH神经元中诱导LTP。相反，GluR2突变体的SDH中HFS-LTD的诱导减少。这些结果表明，AMPAR GluR2亚基在调节突触可塑性方面具有重要作用，这可能与病理状态下的持久超敏反应相关。
