AMPA受体参与的出生后大鼠海马发育早期的电生理学特点

Electrophysiological characteristics of hippocampal postnatal early development mediated by AMPA receptors in rats

本研究旨在探讨α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体参与的出生后大鼠海马发育早期的电生理学特点。选择出生后0.5月龄、1月龄、2月龄和3月龄Wistar大鼠共计48只(每组各12只)。应用全细胞膜片钳技术及MED64平面微电极阵列技术检测海马CA1区锥体神经元的被动膜特性及AMPA受体参与的自发兴奋性突触后电流(spontaneous exctitatory postsynaptic current,sEPSC)和场兴奋性突触后电位(field excitatory postsynaptic potential,fEPSP)。结果显示,海马CA1区锥体神经元在出生后0.5～3月龄期间,在被动膜特性方面表现为:膜电容与静息膜电位无显著性变化;膜输入电阻与时间常数均显著下降。在主动膜特性方面,呈现出阶段性变化:0.5～1月龄期间,s EPSC的反应表现为:振幅显著升高,频率明显增大,上升时间及下降时间显著增加;1～3月龄期间,sEPSC的反应特性与0.5～1月龄期间相反。此外,0.5～3月龄期间,海马CA1区诱发出的f EPSP范围明显扩大,而幅值显著减小;各月龄海马CA1区诱发出的fEPSP幅值均可被AMPA受体竞争性拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮(CNQX)明显降低。以上结果提示,在出生后大鼠海马发育早期过程中,AMPA受体作为调节突触传递和突触联系的主要兴奋性受体,可以促进海马的发育及功能成熟。

The present study was aimed to investigate the electrophysiological characteristics of hippocampal postnatal early development mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid（AMPA） receptors in rats. Forty-eight Wistar rats were divided into postnatal 0.5-, 1-, 2-and 3-month groups（n = 12）. Spontaneous excitatory postsynaptic currents（sEPSCs） and field excitatory postsynaptic potentials（fEPSPs） mediated by AMPA receptors were recorded to evaluate the changes in the intrinsic membraneproperties of hippocampal CA1 pyramidal neurons by using patch-clamp and MED64 planar microelectrode array technique respectively. The results showed that, during the period of postnatal 0.5–3 months, some of the intrinsic membrane properties of hippocampal CA1 pyramidal neurons, such as the membrane capacitance（Cm） and the resting membrane potential（RMP）, showed no significant changes, while the membrane input resistance（Rin） and the time constant（τ） of the cells were decreased significantly. The amplitude, frequency and kinetics（both rise and decay times） of sEPSCs were significantly increased during the period of postnatal 0.5–1 month, but they were all decreased during the period of postnatal 1–3 months. In addition, the range of evoked fEPSPs in hippocamal CA1 region was significantly expanded, but the fEPSP amplitudes were decreased significantly during the period of postnatal 0.5–3 months. Furthermore, the evoked fEPSPs could be significantly inhibited by extracellular application of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione（CNQX）. These results suggest that AMPA receptor may act as a major type of excitatory receptor to regulate synaptic transmission and connections during the early stage of hippocampal postnatal development, which promotes the development and functional maturation of hippocampus in rats.