Neurokinins robustly activate the majority of septohippocampal cholinergic neurons.
Neurokinins robustly activate the majority of septohippocampal cholinergic neurons.
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神经激肽强烈激活大多数隔海马胆碱能神经元。
DOI：
10.1111/j.1460-9568.2007.05993.x
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Alreja,Meenakshi
中科院分区：
文献类型：
--
作者：
Morozova,Elena;Wu,Min;Dumalska,Iryna;Alreja,Meenakshi
在大脑中，速激肽通过三种克隆的神经激肽（NK）受体起作用，与应激相关的情感障碍有关。Hemokinin-1是一种新的速激肽，据报道，它比NK 2或NK 3受体更喜欢NK 1。虽然NK 1和NK 3受体在大脑中大量表达，但NK 2受体介导的电生理效应很少被描述，因为NK 2受体仅在少数大脑区域表达，如内侧隔核/斜角带核。控制海马记忆功能的内侧隔/斜角带神经元也共定位NK 1和NK 3受体。在功能上，所有三种NK受体的隔内激活增加海马乙酰胆碱释放，并且NK 2受体特别涉及应激诱导的海马乙酰胆碱释放。关于NK对隔海马胆碱能神经元影响的电生理学研究尚缺乏，迄今为止尚未报道脑神经元中hemokinin-1的电生理学作用。在本研究中，我们在大鼠脑切片制备中使用全细胞膜片钳记录检查了多种NK对荧光标记的隔海马胆碱能神经元的电生理学和药理学作用。我们证明，绝大多数隔海马胆碱能细胞通过直接突触后机制被NK 1、NK 2和NK 3受体激动剂以及血激肽1激活。在药理学上，血激肽-1不仅招募NK 1，还招募NK 2和NK 3受体，以激活隔海马胆碱能神经元，这是海马乙酰胆碱的主要来源。
In the brain, tachykinins acting via the three cloned neurokinin (NK) receptors are implicated in stress‐related affective disorders. Hemokinin‐1 is a novel tachykinin that reportedly prefers NK1 to NK2 or NK3 receptors. Although NK1 and NK3 receptors are abundantly expressed in the brain, NK2‐receptor‐mediated electrophysiological effects have rarely been described as NK2 receptors are expressed only in a few brain regions such as the nucleus of the medial septum/diagonal band. Medial septal/diagonal band neurons that control hippocampal mnemonic functions also colocalize NK1 and NK3 receptors. Functionally, intraseptal activation of all three NK receptors increases hippocampal acetylcholine release and NK2 receptors have specifically been implicated in stress‐induced hippocampal acetylcholine release. Electrophysiological studies on the effects of NKs on septohippocampal cholinergic neurons are lacking and electrophysiological effects of hemokinin‐1 have thus far not been reported in brain neurons. In the present study we examined the electrophysiological and pharmacological effects of multiple NKs on fluorescently tagged septohippocampal cholinergic neurons using whole‐cell patch‐clamp recordings in a rat brain slice preparation. We demonstrate that a vast majority of septohippocampal cholinergic cells are activated by NK1, NK2 and NK3 receptor agonists as well as by hemokinin‐1 via direct post‐synaptic mechanisms. Pharmacologically, hemokinin‐1 recruits not only NK1 but also NK2 and NK3 receptors to activate septohippocampal cholinergic neurons that are the primary source of acetylcholine for the hippocampus.