Hypocretin1/OrexinA Axon Targeting of Laterodorsal Tegmental Nucleus Neurons Projecting to the Rat Medial Prefrontal Cortex
Hypocretin1/OrexinA Axon Targeting of Laterodorsal Tegmental Nucleus Neurons Projecting to the Rat Medial Prefrontal Cortex
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DOI：
10.1093/cercor/bhr070
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发表时间：
2011-12-01
期刊：
影响因子：
3.7
通讯作者：
Garzon, Miguel
中科院分区：
文献类型：
--
作者：
del Cid-Pellitero, Esther;Garzon, Miguel
皮质激活和目标导向行为是清醒的特征。特别参与这些现象的一个皮质区域是内侧前额叶皮层（mPFC），它接收来自与唤醒和觉醒有关的脑干结构中含有胆碱能的神经元的许多输入，例如后背被盖核（LDT）。下丘脑分泌素/食欲素 (Hcrt/Ox) 的功能障碍与发作性睡病有关，可维持觉醒并稳定睡眠-觉醒状态。我们的目的是确定 Hcrt1/OxA 轴突是否 (1) 支配投射到 mPFC 的 LDT 神经元，这是一个允许它们维持唤醒和觉醒的目标，以及 (2) 优先针对胆碱能 LDT 神经元而不是非胆碱能 LDT 神经元。将逆行示踪剂 Fluorogold (FG) 注射到大鼠 mPFC 中，并在 LDT 中测定抗 FG 和抗胆碱乙酰转移酶 (ChAT) 或抗 Hcrt1/OxA 抗血清的双重免疫标记。此外，通过在其他未注射动物中进行双重抗 Hcrt1/OxA 和抗 ChAT 检测，确定了胆碱能 LDT 神经元的实际 Hcrt1/OxA 靶向。许多 LDT FG 标记的神经元是胆碱能的 (52.05 +/- 3.72%)。在轴突内的细胞质和颗粒囊泡中观察到 Hcrt1/OxA 免疫沉淀。一些含有 Hcrt1/OxA 的轴突与未标记 (46/438) 或 FG 标记 (7/438) 树突建立了不对称兴奋型突触。三分之一的目标神经元被 ChAT 标记。 Hcrt1/OxA 对投射到 mPFC 的 LDT 神经元的兴奋性输入可能有助于嗜睡症患者受损的 Hcrt/Ox 的觉醒增强作用。
Cortical activation and goal-directed behaviors characterize wakefulness. One cortical region especially involved in these phenomena is the medial prefrontal cortex (mPFC), which receives many inputs from cholinergic-containing neurons in brain stem structures implicated in arousal and wakefulness, such as the laterodorsal tegmental nucleus (LDT). Hypocretins/orexins (Hcrt/Ox), whose dysfunction is linked to narcolepsy, maintains arousal and stabilizes sleep-wakefulness states. We aim to determine if Hcrt1/OxA axons (1) innervate LDT neurons projecting to the mPFC, a target that would allow them to sustain arousal and wakefulness, and (2) target preferentially cholinergic versus noncholinergic LDT neurons. The retrograde tracer Fluorogold (FG) was injected in the rat mPFC, and dual immunolabeling of anti-FG and either anti-choline acetyltransferase (ChAT) or anti-Hcrt1/OxA antisera was determined in LDT. Also, actual Hcrt1/OxA targeting of cholinergic LDT neurons was ascertained by dual anti-Hcrt1/OxA and anti-ChAT detection in additional noninjected animals. Many LDT FG-labeled neurons were cholinergic (52.05 +/- 3.72%). Hcrt1/OxA immunoprecipitate was observed in cytoplasm and granular vesicles within axons. Some Hcrt1/OxA-containing axons established asymmetric excitatory-type synapses with either unlabeled (46/438) or FG-labeled (7/438) dendrites. One-third of the target neurons were ChAT labeled. Hcrt1/OxA excitatory input to LDT neurons projecting to mPFC probably contributes to the wakefulness-enhancing actions of Hcrt/Ox impaired in narcoleptics.