Synaptic Plasticity of Hypothalamic Neurons

下丘脑中的巨细胞神经内分泌细胞负责合成和释放 加压素和催产素，参与液体平衡、血压调节、分娩的神经激素 和哺乳期。这些神经元的大部分突触调节是由神经递质控制的。 谷氨酸、GABA和去甲肾上腺素。解剖学研究表明，巨噬细胞 神经分泌系统在以下条件下发生戏剧性的神经元-神经胶质和突触重组 脱水，代表了成人大脑中一种独特的生理结构可塑性模型。这 包括大细胞神经元周围的胶质突起的广泛回缩和形成 新的谷氨酸能、GABA能和去甲肾上腺素能突触。我们假设这些结构性变化 导致谷氨酸、GABA和去甲肾上腺素能突触对大细胞神经元的输入增加 以及它们的转运体介导的清除减少，导致环境中 这些神经递质的细胞外水平。我们将通过在未经治疗的情况下进行比较来检验第一个假设 和脱水大鼠脑内大脑皮层谷氨酸和氨基丁酸能突触传入水平 视上核，以及通过激活突触前代谢对这些输入的调制 周围神经递质水平的感受器。我们推测谷氨酸表达的变化可能是 负责由脱水引起的结构可塑性的诱导，就像这些受体已经 与结构可塑性有关的突触接触的形成和稳定 发育中的和成年的大脑。我们将通过评估脱水引起的细胞周期变化来检验这一假说。 谷氨酸受体亚基的表达及其在正常动物中的变化 通过病毒在活体中传递特定的受体亚单位基因。这些研究旨在实现 两个目标：1)确定脱水引起的神经元-神经胶质结构变化是否会导致 突触神经支配和大细胞神经元兴奋性的变化，以及2)确定 谷氨酸受体表达的改变是否是导致结构改变的原因 与脱水有关。这些研究的成功完成将揭示生理学 在脱水条件下观察到的解剖变化的意义，并将为深入了解 导致这些变化的分子机制。

Magnocellular neuroendocrine cells in the hypothalamus are responsible for the synthesis and release of vasopressin and oxytocin, neurohormones involved in fluid balance, blood pressure regulation, parturition and lactation. Much of the synaptic regulation of these neurons is under the control of the neurotransmitters glutamate, GABA and norepinephrine. Anatomical studies have shown that the magnocellular neurosecretory systems undergo dramatic neuronal-glial and synaptic reorganization under conditions of dehydration, representing a unique model of physiologically linked structural plasticity in the adult brain. This includes extensive retraction of glial processes from around the magnocellular neurons and the formation of new glutamatergic, GABAergic and noradrenergic synapses. We postulate that these structural changes lead to an increase in the glutamate, GABA and noradrenergic synaptic inputs to the magnocellular neurons as well as to a decrease in their transporter-mediated clearance, resulting in an increase in the ambient extracellular levels of these neurotransmitters. We will test this first hypothesis by comparing in untreated and dehydrated rats the levels of glutamatergic and GABAergic synaptic inputs to magnoceUular neurons of the supraoptic nucleus, as well as the modulation of these inputs by activation of presynaptic metabotropic receptors by ambient neurotransmitter levels. We posit that changes in the expression of glutamate may be responsible for the induction of the structural plasiticity caused by dehydration, as these receptors have been implicated in the formation and stabilization of synaptic contacts associated with structural plasticity in developing and adult brain. We will test this hypothesis by assessing dehydration-induced changes in the expression of specific glutamate receptor subunits, and by altering subunit expression in normal animals through viral delivery of specific receptor subunit genes in viva. These studies are designed to accomplish two goals: 1) to determine whether the neuronal-glial structural changes induced by dehydration lead to changes in the synaptic innervation and in the excitability of magnocellular neurons, and 2) to determine whether changes in glutamate receptor expression are causal in the induction of the structural changes associated with dehydration. The successful completion of these studies will reveal the physiological significance of anatomical changes observed under conditions of dehydration, and will provide insight into the molecular mechanisms responsible for these changes.