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沉默的N-甲基-D-天冬氨酸受体介导的突触在大鼠脊髓背角中受到发育调控。

Silent NMDA receptor-mediated synapses are developmentally regulated in the dorsal horn of the rat spinal cord.

作者信息

Baba H, Doubell T P, Moore K A, Woolf C J

机构信息

Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.

出版信息

J Neurophysiol. 2000 Feb;83(2):955-62. doi: 10.1152/jn.2000.83.2.955.

DOI:10.1152/jn.2000.83.2.955
PMID:10669507
Abstract

In vitro whole cell patch-clamp recording techniques were utilized to study silent pure-N-methyl-D-aspartate (NMDA) receptor-mediated synaptic responses in lamina II (substantia gelatinosa, SG) and lamina III of the spinal dorsal horn. To clarify whether these synapses are present in the adult and contribute to neuropathic pain, transverse lumbar spinal cord slices were prepared from neonatal, naive adult and adult sciatic nerve transected rats. In neonatal rats, pure-NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) were elicited in SG neurons either by focal intraspinal stimulation (n = 15 of 20 neurons) or focal stimulation of the dorsal root (n = 2 of 7 neurons). In contrast, in slices from naive adult rats, no silent pure-NMDA EPSCs were recorded in SG neurons following focal intraspinal stimulation (n = 27), and only one pure-NMDA EPSC was observed in lamina III (n = 23). Furthermore, in rats with chronic sciatic nerve transection, pure-NMDA EPSCs were elicited by focal intraspinal stimulation in only 2 of 45 SG neurons. Although a large increase in Abeta fiber evoked mixed alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptor-mediated synapses was detected after sciatic nerve injury, Abeta fiber-mediated pure-NMDA EPSCs were not evoked in SG neurons by dorsal root stimulation. Pure-NMDA receptor-mediated EPSCs are therefore a transient, developmentally regulated phenomenon, and, although they may have a role in synaptic refinement in the immature dorsal horn, they are unlikely to be involved in receptive field plasticity in the adult.

摘要

利用体外全细胞膜片钳记录技术,研究脊髓背角II层(胶状质,SG)和III层中沉默的纯N-甲基-D-天冬氨酸(NMDA)受体介导的突触反应。为了阐明这些突触是否存在于成年个体中并导致神经性疼痛,制备了新生大鼠、未受伤成年大鼠和成年坐骨神经横断大鼠的腰段脊髓横切片。在新生大鼠中,通过脊髓内局部刺激(20个神经元中有15个)或背根局部刺激(7个神经元中有2个),在SG神经元中诱发了纯NMDA受体介导的兴奋性突触后电流(EPSC)。相比之下,在未受伤成年大鼠的切片中,脊髓内局部刺激后,SG神经元中未记录到沉默的纯NMDA EPSC(n = 27),在III层仅观察到一个纯NMDA EPSC(n = 23)。此外,在慢性坐骨神经横断的大鼠中,45个SG神经元中只有2个通过脊髓内局部刺激诱发了纯NMDA EPSC。虽然在坐骨神经损伤后检测到β纤维诱发的混合α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)和NMDA受体介导的突触大量增加,但背根刺激未在SG神经元中诱发β纤维介导的纯NMDA EPSC。因此,纯NMDA受体介导的EPSC是一种短暂的、受发育调控的现象,虽然它们可能在未成熟背角的突触精细化中起作用,但它们不太可能参与成年个体的感受野可塑性。

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