Excitatory mechanisms in the suprachiasmatic nucleus: The role of AMPA/KA glutamate receptors
Excitatory mechanisms in the suprachiasmatic nucleus: The role of AMPA/KA glutamate receptors
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DOI：
10.1152/jn.2002.88.2.817
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发表时间：
2002-08-01
影响因子：
2.5
通讯作者：
Colwell, CS
中科院分区：
文献类型：
--
作者：
Michel, S;Itri, J;Colwell, CS
多种证据表明，光对哺乳动物昼夜节律系统的影响是通过视网膜神经节细胞直接投射到视交叉上核（SCN）介导的。这种突触连接是谷氨酸能的，谷氨酸的释放由n -甲基- d -天冬氨酸（NMDA）和氨基-甲基本体酸/海因酸（AMPA/KA）嗜离子性谷氨酸受体（GluRs）检测。众所周知，NMDA GluRs在调节光对昼夜节律系统的影响中起着关键作用；然而，AMPA/KA GluRs的作用受到的关注较少。在本研究中，我们试图更好地理解AMPA/ ka介导的电流在基于SCN的昼夜节律系统中的作用。首先，利用全细胞膜片钳电生理技术测量SCN神经元的自发兴奋性突触后电流（sEPSCs）。这些电流在SCN中广泛存在，而不仅仅局限于视网膜受体区域。sEPSC的频率和幅值不随日周期变化。同样，外源性AMPA在SCN神经元上的应用所引起的电流在SCN内广泛存在，并且在其大小上不表现出昼夜节律。利用荧光技术估计ampa诱导的SCN神经元钙（Ca2+）浓度变化。结果表明，ampa诱发的Ca2+瞬态在SCN中广泛存在，并且ampa诱导的Ca2+瞬态的强度在夜间达到峰值，存在每日节律。用受体阻滞剂阻断AMPA/KA GluRs本身可以减少一些SCN神经元的自发放电，并降低静息Ca2+水平，提示强直性谷氨酸能兴奋。最后，利用免疫组织化学技术描述了SCN中ampa偏好的GluR亚基GluR1和GluR2/3s的表达。总之，我们的数据表明AMPA/KA GluRs介导的谷氨酸能突触传递在整个SCN突触回路中起着重要作用。
A variety of evidence suggests that the effects of light on the mammalian circadian system are mediated by direct retinal ganglion cell projection to the suprachiasmatic nucleus (SCN). This synaptic connection is glutamatergic and the release of glutamate is detected by both N-methyl-D-asparate (NMDA) and amino-methyl proprionic acid/kainate (AMPA/KA) iontotropic glutamate receptors (GluRs). It is well established that NMDA GluRs play a critical role in mediating the effects of light on the circadian system; however, the role of AMPA/KA GluRs has received less attention. In the present study, we sought to better understand the contribution of AMPA/KA-mediated currents in the circadian system based in the SCN. First, whole cell patch-clamp electrophysiological techniques were utilized to measure spontaneous excitatory postsynaptic currents (sEPSCs) from SCN neurons. These currents were widespread in the SCN and not just restricted to the retino-recipient region. The sEPSC frequency and amplitude did not vary with the daily cycle. Similarly, currents evoked by the exogenous application of AMPA onto SCN neurons were widespread within the SCN and did not exhibit a diurnal rhythm in their magnitude. Fluorometric techniques were utilized to estimate AMPA-induced calcium (Ca2+) concentration changes in SCN neurons. The resulting data indicate that AMPA-evoked Ca2+ transients were widespread in the SCN and that there was a daily rhythm in the magnitude of AMPA-induced Ca2+ transients that peaked during the night. By itself, blocking AMPA/KA GluRs with a receptor blocker decreased the spontaneous firing of some SCN neurons as well as reduced resting Ca2+ levels, suggesting tonic glutamatergic excitation. Finally, immunohistochemical techniques were used to describe expression of the AMPA-preferring GluR subunits GluR1 and GluR2/3s within the SCN. Overall, our data suggest that glutamatergic synaptic transmission mediated by AMPA/KA GluRs play an important role throughout the SCN synaptic circuitry.