Chemogenetic modulation of histaminergic neurons in the tuberomamillary nucleus alters territorial aggression and wakefulness.
Chemogenetic modulation of histaminergic neurons in the tuberomamillary nucleus alters territorial aggression and wakefulness.
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DOI：
10.1038/s41598-021-95497-3
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发表时间：
2021-09-09
影响因子：
4.6
通讯作者：
Okamura N
中科院分区：
文献类型：
--
作者：
Naganuma F;Nakamura T;Kuroyanagi H;Tanaka M;Yoshikawa T;Yanai K;Okamura N
由设计药物激活的设计受体（DREADD）技术被广泛用于在行为任务期间调节特定神经元群体的活动。然而，DREADDs诱导的结节乳头核（HATMN神经元）中组胺能神经元的调节对睡眠-觉醒周期产生了不一致的影响，这可能是由于使用Hdc-Cre小鼠驱动Cre重组酶和DREADDs在靶区域外的活性。此外，以前的DREADDs研究没有检查运动活动和攻击行为，这也是由大脑组胺水平调节的。在本研究中，我们研究了HATMN激活和抑制对具有最小的Cre重组酶非靶表达的Hdc-Cre小鼠的自发活动、攻击行为和睡眠-觉醒周期的影响。化学激活HATMN适度增强运动活动在一个新的开放领域。HATMN神经元的激活显着增强侵略行为的居民入侵者测试。通过HATMN化学活化，觉醒增加，非快速眼动（NREM）睡眠减少1小时。相反，HATMN化学抑制减少觉醒，增加NREM睡眠6小时。HATMN调节引起的觉醒的这些变化与警觉状态的维持有关。这些结果表明HATMN神经元对探索活动，领土侵略和唤醒维持的影响。
Designer receptor activated by designer drugs (DREADDs) techniques are widely used to modulate the activities of specific neuronal populations during behavioural tasks. However, DREADDs-induced modulation of histaminergic neurons in the tuberomamillary nucleus (HATMN neurons) has produced inconsistent effects on the sleep–wake cycle, possibly due to the use of Hdc-Cre mice driving Cre recombinase and DREADDs activity outside the targeted region. Moreover, previous DREADDs studies have not examined locomotor activity and aggressive behaviours, which are also regulated by brain histamine levels. In the present study, we investigated the effects of HATMN activation and inhibition on the locomotor activity, aggressive behaviours and sleep–wake cycle of Hdc-Cre mice with minimal non-target expression of Cre-recombinase. Chemoactivation of HATMN moderately enhanced locomotor activity in a novel open field. Activation of HATMN neurons significantly enhanced aggressive behaviour in the resident–intruder test. Wakefulness was increased and non-rapid eye movement (NREM) sleep decreased for an hour by HATMN chemoactivation. Conversely HATMN chemoinhibition decreased wakefulness and increased NREM sleep for 6 h. These changes in wakefulness induced by HATMN modulation were related to the maintenance of vigilance state. These results indicate the influences of HATMN neurons on exploratory activity, territorial aggression, and wake maintenance.
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影响因子：
7.3
作者：
BRISTOW, LJ;BENNETT, GW
通讯作者：
BENNETT, GW
DOI：
10.1073/pnas.93.23.13316
发表时间：
1996-11-12
影响因子：
11.1
作者：
Inoue, I;Yanai, K;Watanabe, T
通讯作者：
Watanabe, T
影响因子：
4.6
作者：
Naganuma F;Nakamura T;Yoshikawa T;Iida T;Miura Y;Kárpáti A;Matsuzawa T;Yanai A;Mogi A;Mochizuki T;Okamura N;Yanai K
通讯作者：
Yanai K
影响因子：
3
作者：
Blandina P;Munari L;Provensi G;Passani MB
通讯作者：
Passani MB
DOI：
10.1073/pnas.1604841113
发表时间：
2016-05-10
影响因子：
11.1
作者：
Fabbri, Roberta;Furini, Cristiane Regina Guerino;Blandina, Patrizio
通讯作者：
Blandina, Patrizio