Awake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks.

Awake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks.
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DOI:
10.1038/ncomms11395
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发表时间:
2016-04-22
影响因子:
16.6
通讯作者:
Burdakov D
Burdakov D
中科院分区:
综合性期刊1区
文献类型:
--
作者:
González JA;Iordanidou P;Strom M;Adamantidis A;Burdakov D

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外侧下丘脑(LH)控制能量平衡。LH黑色素浓集激素(MCH)和食欲素/下丘脑泌素(OH)神经元分别介导能量积累和消耗。MCH细胞促进记忆和适当的刺激-奖励关联;它们的失活破坏能量最佳行为并导致体重减轻。然而,MCH细胞在清醒期间的动力学是未知的,因此不清楚它们是否在感觉处理期间差异地参与大脑活动。从分子定义的LH神经元在清醒的自由活动的小鼠群体的光纤记录,我们表明,MCH神经元产生条件性群体爆发。这种MCH细胞活性与新奇探索相关,受到压力的抑制,并且被OH细胞活性反向预测。此外,我们获得了MCH和OH细胞的单突触输入的全脑地图,并证明了杏仁核和终纹床核中的VGAT神经元抑制MCH细胞的光遗传学。这些数据揭示了感觉统合过程中细胞类型特异性LH动力学,并确定了MCH神经元的直接神经控制器。 表达黑色素浓集激素(MCH)的下丘脑神经元通过协调行为和代谢来维持体重,但对其内在调节知之甚少。在这里,Gonzalez和他的同事揭示了他们在清醒期间与行为相关的动态,并绘制了他们的大脑神经输入。
The lateral hypothalamus (LH) controls energy balance. LH melanin-concentrating-hormone (MCH) and orexin/hypocretin (OH) neurons mediate energy accumulation and expenditure, respectively. MCH cells promote memory and appropriate stimulus-reward associations; their inactivation disrupts energy-optimal behaviour and causes weight loss. However, MCH cell dynamics during wakefulness are unknown, leaving it unclear if they differentially participate in brain activity during sensory processing. By fiberoptic recordings from molecularly defined populations of LH neurons in awake freely moving mice, we show that MCH neurons generate conditional population bursts. This MCH cell activity correlates with novelty exploration, is inhibited by stress and is inversely predicted by OH cell activity. Furthermore, we obtain brain-wide maps of monosynaptic inputs to MCH and OH cells, and demonstrate optogenetically that VGAT neurons in the amygdala and bed nucleus of stria terminalis inhibit MCH cells. These data reveal cell-type-specific LH dynamics during sensory integration, and identify direct neural controllers of MCH neurons. Hypothalamic neurons expressing melanin-concentrating-hormone (MCH) maintain body weight by orchestrating behaviour and metabolism, but little is known about their intrinsic regulation. Here, Gonzalez and colleagues reveal their behaviour-related dynamics during wakefulness, and map their brain-wide neural inputs.