Memory retrieval of inhibitory avoidance requires histamine H1 receptor activation in the hippocampus
Memory retrieval of inhibitory avoidance requires histamine H1 receptor activation in the hippocampus
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DOI：
10.1073/pnas.1604841113
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发表时间：
2016-05-10
影响因子：
11.1
通讯作者：
Blandina, Patrizio
中科院分区：
文献类型：
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作者：
Fabbri, Roberta;Furini, Cristiane Regina Guerino;Blandina, Patrizio
提取是一个动态的过程，可能需要神经调节信号。在这里，我们报告说，大脑组胺能系统的完整性是必要的检索抑制性回避（IA）的记忆，因为大鼠耗尽组胺通过侧脑室注射的α-氟甲基组氨酸（α-FMHis），组氨酸脱羧酶的自杀抑制剂，显示受损的IA记忆测试后2天训练。在训练后24 h，当IA记忆痕迹已经形成时，施用a-FMHis。在保留测试前10分钟，在海马CA 1区的脑组织胺耗尽大鼠（因此，健忘症）中输注组胺恢复IA记忆，但在基底外侧杏仁核（BLA）或腹内侧前额叶皮层（vmPFC）中输注时无效。选择性H-1和H-2受体激动剂的CA 1内注射表明，组胺通过激活H1受体发挥其作用。值得注意的是，H1受体拮抗剂pyrilamine破坏IA记忆检索大鼠，从而强烈支持内源性组胺的积极参与，90分钟后保留测试，c-Fos阳性神经元显着减少在CA 1的a-FMHis治疗的大鼠，显示健忘症与对照组相比。我们还发现，与对照组相比，α-FMMis治疗组动物的CA 1中磷酸化cAMP反应元件结合蛋白（pCREB）水平降低。pCREB水平的增加与相关记忆的检索有关。靶向组胺能系统可能会改变情绪记忆的检索;因此，组胺能配体可能会减少功能失调的厌恶性记忆，并提高暴露心理疗法的疗效。
Retrieval represents a dynamic process that may require neuromodulatory signaling. Here, we report that the integrity of the brain histaminergic system is necessary for retrieval of inhibitory avoidance (IA) memory, because rats depleted of histamine through lateral ventricle injections of a-fluoromethylhistidine (a-FMHis), a suicide inhibitor of histidine decarboxylase, displayed impaired IA memory when tested 2 d after training. a-FMHis was administered 24 h after training, when IA memory trace was already formed. Infusion of histamine in hippocampal CA1 of brain histamine-depleted rats (hence, amnesic) 10 min before the retention test restored IA memory but was ineffective when given in the basolateral amygdala (BLA) or the ventral medial prefrontal cortex (vmPFC). Intra-CA1 injections of selective H-1 and H-2 receptor agonists showed that histamine exerted its effect by activating the H1 receptor. Noteworthy, the H1 receptor antagonist pyrilamine disrupted IA memory retrieval in rats, thus strongly supporting an active involvement of endogenous histamine; 90 min after the retention test, c-Fos-positive neurons were significantly fewer in the CA1s of a-FMHis-treated rats that displayed amnesia compared with in the control group. We also found reduced levels of phosphorylated cAMP-responsive element binding protein (pCREB) in the CA1s of a-FMHis-treated animals compared with in controls. Increases in pCREB levels are associated with retrieval of associated memories. Targeting the histaminergic system may modify the retrieval of emotional memory; hence, histaminergic ligands might reduce dysfunctional aversive memories and improve the efficacy of exposure psychotherapies.