Chemogenetic activation of histamine neurons promotes retrieval of apparently lost memories.

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Yuto Yokoi, Ayame Kubo, Kyoka Nishimura, Yuki Takamura, Yoshikazu Morishita, Masabumi Minami, Hiroshi Nomura
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Abstract

Memory retrieval can become difficult over time, but it is important to note that memories that appear to be forgotten might still be stored in the brain, as shown by their occasional spontaneous retrieval. Histamine in the central nervous system is a promising target for facilitating the recovery of memory retrieval. Our previous study demonstrated that histamine H3 receptor (H3R) inverse agonists/antagonists, activating histamine synthesis and release, enhance activity in the perirhinal cortex and help in retrieving forgotten long-term object recognition memories. However, it is unclear whether enhancing histaminergic activity alone is enough for the recovery of memory retrieval, considering that H3Rs are also located in other neuron types and affect the release of multiple neurotransmitters. In this study, we employed a chemogenetic method to determine whether specifically activating histamine neurons in the tuberomammillary nucleus facilitates memory retrieval. In the novel object recognition test, control mice did not show a preference for objects based on memory 1 week after training, but chemogenetic activation of histamine neurons before testing improved memory retrieval. This selective activation did not affect the locomotor activity or anxiety-related behavior. Administering an H2R antagonist directly into the perirhinal cortex inhibited the recovery of memory retrieval induced by the activation of histamine neurons. Furthermore, we utilized the Barnes maze test to investigate whether chemogenetic activation of histamine neurons influences the retrieval of forgotten spatial memories. Control mice explored all the holes in the maze equally 1 week after training, whereas mice with chemogenetically activated histamine neurons spent more time around the target hole. These findings indicate that chemogenetic activation of histamine neurons in the tuberomammillary nucleus can promote retrieval of seemingly forgotten object recognition and spatial memories.

组胺神经元的化学激活可促进明显丢失记忆的恢复。
随着时间的推移,记忆检索可能会变得困难,但重要的是要注意,看似已被遗忘的记忆可能仍然储存在大脑中,这一点从它们偶尔会自发检索到就可以看出。中枢神经系统中的组胺是促进记忆恢复的一个很有希望的靶点。我们之前的研究表明,组胺 H3 受体(H3R)反向激动剂/拮抗剂能激活组胺的合成和释放,增强边缘皮层的活动,有助于找回遗忘的长期物体识别记忆。然而,考虑到 H3Rs 还分布在其他神经元类型中,并影响多种神经递质的释放,目前还不清楚仅增强组胺能活性是否足以恢复记忆检索。在这项研究中,我们采用了一种化学遗传学方法来确定特异性激活结节乳突核中的组胺神经元是否能促进记忆恢复。在新物体识别测试中,对照组小鼠在训练一周后并没有表现出基于记忆的物体偏好,但在测试前通过化学方法激活组胺神经元可改善记忆检索。这种选择性激活不会影响小鼠的运动活动或与焦虑相关的行为。在脐周皮层直接注射 H2R 拮抗剂可抑制组胺神经元激活引起的记忆恢复。此外,我们还利用巴恩斯迷宫试验来研究组胺神经元的化学激活是否会影响遗忘空间记忆的检索。对照组小鼠在训练1周后同样探索了迷宫中的所有洞口,而化学激活组胺神经元的小鼠则在目标洞口周围花费了更多时间。这些研究结果表明,用化学方法激活小结节乳突核中的组胺神经元可促进看似被遗忘的物体识别和空间记忆的恢复。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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