Increased tonic activation of presynaptic metabotropic glutamate receptors in the rat supraoptic nucleus following chronic dehydration
Increased tonic activation of presynaptic metabotropic glutamate receptors in the rat supraoptic nucleus following chronic dehydration
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DOI：
10.1113/jphysiol.2003.042739
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发表时间：
2003-09-15
影响因子：
5.5
通讯作者：
Tasker, JG
中科院分区：
文献类型：
--
作者：
Boudaba, C;Linn, DM;Tasker, JG
慢性脱水诱导下丘脑视上核（SON）的结构变化，包括谷氨酸突触增加和星形胶质细胞过程的收缩。我们在急性下丘脑切片进行了全细胞记录，以确定这些变化是否通过增加SON中的环境谷氨酸来增加突触前代谢型谷氨酸受体（mGluRs）的紧张性激活。突触前III组mGluRs的激活导致SON神经元中的微型兴奋性突触后电流（mEPSC）频率降低，与未处理大鼠（-41.7%）相比，脱水大鼠（-27.8%）的切片中mGluRs的频率显著减弱，表明脱水期间环境谷氨酸对mGluRs的基础占用率较高。阻断第III组mGluRs导致mEPSC频率增加，脱水大鼠脑片（+42.8%）的mEPSC频率显著高于未处理大鼠（+31.4%），表明脱水期间环境谷氨酸对突触前mGluRs的强直性激活更大。通过抑制星形胶质细胞谷氨酸摄取来增加环境谷氨酸水平，由于突触前mGluRs的激活增加，导致mEPSC频率降低。与来自未处理大鼠的切片（-48.8%）相比，来自脱水大鼠的切片（-35.4%）中这一点减弱，表明脱水期间星形胶质细胞谷氨酸摄取减少。免疫化学分析显示，一个强大的表达GLT-1转运蛋白的SON，这是减少在SON冲床脱水大鼠相比，未经处理的控制。因此，脱水导致谷氨酸末端突触前mGluRs的强直性激活增加，与谷氨酸缓冲能力的降低一致。谷氨酸释放概率的降低可以补偿在脱水期间发生的谷氨酸释放位点的增加。
Chronic dehydration induces structural changes in the hypothalamic supraoptic nucleus (SON), including increased glutamate synapses and retraction of astroglial processes. We performed whole-cell recordings in acute hypothalamic slices to determine whether these changes increase tonic activation of presynaptic metabotropic glutamate receptors (mGluRs) by increasing ambient glutamate in the SON. Activation of presynaptic group III mGluRs caused a decrease in the frequency of miniature excitatory postsynaptic currents (mEPSCs) in SON neurones that was significantly attenuated in slices from dehydrated rats (-27.8%) compared with untreated rats (-41.7%), suggesting a higher basal occupancy of mGluRs by ambient glutamate during dehydration. Blocking group III mGluRs caused an increase in the frequency of mEPSCs that was significantly higher in slices from dehydrated rats (+42.8%) than untreated rats (+31.4%), suggesting greater tonic activation of presynaptic mGluRs by ambient glutamate during dehydration. Increasing ambient glutamate levels by inhibiting astrocyte glutamate uptake resulted in a decrease in mEPSC frequency due to increased activation of presynaptic mGluRs. This was attenuated in slices from dehydrated rats (-35.4%) compared with slices from untreated rats (-48.8%), suggesting diminished astrocytic glutamate uptake during dehydration. Immunochemical analyses revealed a robust expression of the GLT-1 transporter protein in the SON, which was diminished in SON punches from dehydrated rats compared with untreated controls. Thus, dehydration leads to increased tonic activation of presynaptic mGluRs on glutamate terminals, consistent with a decrease in glutamate buffering capacity. The resulting reduction in glutamate release probability may compensate for the increase in glutamate release sites that occurs during dehydration.