Dehydration-induced synaptic plasticity in magnocellular neurons of the hypothalamic supraoptic nucleus
Dehydration-induced synaptic plasticity in magnocellular neurons of the hypothalamic supraoptic nucleus
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DOI：
10.1210/en.2004-0702
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发表时间：
2004-11-01
期刊：
影响因子：
4.8
通讯作者：
Tasker, JG
中科院分区：
文献类型：
--
作者：
Di, S;Tasker, JG
去甲肾上腺素在调节下丘脑神经内分泌功能中起重要作用，很大程度上是通过调节突触谷氨酸和γ-氨基丁酸(GABA)的释放来实现的。下丘脑大细胞神经内分泌细胞在激素释放增加的情况下发生突触组织的急剧变化，包括谷氨酸能、GABA能和去甲肾上腺素能突触的数量增加。我们利用下丘脑脑片全细胞记录技术研究了慢性脱水诱导的大鼠视上核巨细胞神经元的功能可塑性。脱水大鼠对大细胞神经元的谷氨酸和GABA释放增加，表现为突触后自发兴奋性电流(29%)和抑制性电流(33%)的频率增加。谷氨酸释放的变化可能是由于释放部位的增加，因为成对脉冲促进分析没有揭示递质释放的概率的变化。在未经治疗的大鼠中，去甲肾上腺素促进了谷氨酸的释放，并减弱了对大细胞神经元的GABA释放。脱水导致去甲肾上腺素的作用显著增强，使去甲肾上腺素引起的谷氨酸释放增加和GABA释放减少两倍。去甲肾上腺素的剂量-反应曲线随着脱水而左移，显示去甲肾上腺素的敏感性增加。因此，脱水导致视上大细胞神经元谷氨酸和GABA释放增加，去甲肾上腺素对谷氨酸释放的促进作用和对GABA释放的抑制作用明显增强。这种突触可塑性有望增加大细胞神经元的兴奋性，并支持慢性脱水患者体内观察到的增强的爆发能力和促进激素分泌。
Norepinephrine plays a critical role in the regulation of hypothalamic neuroendocrine function, in large part through modulation of synaptic glutamate and gamma-aminobutyric acid (GABA) release. Hypothalamic magnocellular neuroendocrine cells undergo dramatic changes in synaptic organization under conditions of increased hormone release, including increased numbers of glutamatergic, GABAergic and noradrenergic synapses. We studied the functional plasticity of magnocellular neurons of the rat supraoptic nucleus induced by chronic dehydration using whole-cell recordings in hypothalamic slices. Dehydrated rats showed increases in glutamate and GABA release onto magnocellular neurons, as evidenced by an increase in the frequency of spontaneous excitatory (29%) and inhibitory (33%) postsynaptic currents. The change in glutamate release was likely due to increased numbers of release sites because paired-pulse facilitation analysis did not reveal a change in the probability of transmitter release. In untreated rats, norepinephrine facilitates glutamate release and attenuates GABA release onto magnocellular neurons. Dehydration resulted in a marked enhancement of norepinephrine's actions, doubling both the norepinephrine-induced increase in glutamate release and decrease in GABA release. The norepinephrine dose-response curve was shifted to the left with dehydration, revealing an increase in norepinephrine sensitivity. Thus, dehydration leads to an increase in glutamate and GABA release onto supraoptic magnocellular neurons as well as a marked enhancement of the facilitatory effect of norepinephrine on glutamate release and inhibitory effect on GABA release. This synaptic plasticity would be expected to increase the excitability of the magnocellular neurons and support the enhanced bursting capacity and facilitated hormone secretion observed in vivo with chronic dehydration.