Neurons in the Dorsomedial Hypothalamus Promote, Prolong, and Deepen Torpor in the Mouse.
Neurons in the Dorsomedial Hypothalamus Promote, Prolong, and Deepen Torpor in the Mouse.
复制标题
下丘脑背内侧区的神经元促进、延长和加深小鼠的昏睡。
DOI：
10.1523/jneurosci.2102-21.2022
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发表时间：
2022-05-25
影响因子：
5.3
通讯作者：
Pickering, Anthony
中科院分区：
文献类型：
--
作者：
Ambler, Michael;Hitrec, Timna;Wilson, Andrew;Cerri, Matteo;Pickering, Anthony
麻痹是一种自然发生的低代谢、低体温状态，由多种动物参与，以响应营养物质供需之间的不平衡。最近的工作已经确定了一些关键的神经元群体参与日常麻木诱导小鼠，特别是，从视前区的下丘脑背内侧下丘脑（DMH）的预测。DMH在体温调节、能量消耗控制和昼夜节律中起作用，使其处于有利位置，有助于表现麻木。我们使用活性依赖性遗传TRAPing技术来靶向在雌性小鼠的自然麻痹发作期间活跃的DMH神经元。在热量限制的小鼠中，被麻痹的DMH神经元的化学发生再激活促进了麻痹，导致更长和更深的麻痹发作。化学发生抑制torpor-TRAPed DMH神经元并没有阻止麻痹进入，这表明DMH在控制麻痹中的调节作用。这项工作增加了证据，表明下丘脑的视前区和DMH形成了小鼠下丘脑内控制进入日常休眠的回路的一部分。意义声明日常生活中的异温动物，如小鼠，使用麻木来科普代谢燃料供应不足以维持正常体温的环境。日常麻木包括体温降低，以及心率和新陈代谢的主动抑制。中枢神经系统如何控制这种严重偏离正常稳态的现象尚不清楚，但最近发现了从视前区到下丘脑背内侧的投射。我们证明，背内侧下丘脑包含的神经元，是活跃在昏睡。这些神经元的活动促进了进入和维持麻痹状态，但单独激活它们似乎不足以进入麻痹状态。
Torpor is a naturally occurring, hypometabolic, hypothermic state engaged by a wide range of animals in response to imbalance between the supply and demand for nutrients. Recent work has identified some of the key neuronal populations involved in daily torpor induction in mice, in particular, projections from the preoptic area of the hypothalamus to the dorsomedial hypothalamus (DMH). The DMH plays a role in thermoregulation, control of energy expenditure, and circadian rhythms, making it well positioned to contribute to the expression of torpor. We used activity-dependent genetic TRAPing techniques to target DMH neurons that were active during natural torpor bouts in female mice. Chemogenetic reactivation of torpor-TRAPed DMH neurons in calorie-restricted mice promoted torpor, resulting in longer and deeper torpor bouts. Chemogenetic inhibition of torpor-TRAPed DMH neurons did not block torpor entry, suggesting a modulatory role for the DMH in the control of torpor. This work adds to the evidence that the preoptic area of the hypothalamus and the DMH form part of a circuit within the mouse hypothalamus that controls entry into daily torpor. SIGNIFICANCE STATEMENT Daily heterotherms, such as mice, use torpor to cope with environments in which the supply of metabolic fuel is not sufficient for the maintenance of normothermia. Daily torpor involves reductions in body temperature, as well as active suppression of heart rate and metabolism. How the CNS controls this profound deviation from normal homeostasis is not known, but a projection from the preoptic area to the dorsomedial hypothalamus has recently been implicated. We demonstrate that the dorsomedial hypothalamus contains neurons that are active during torpor. Activity in these neurons promotes torpor entry and maintenance, but their activation alone does not appear to be sufficient for torpor entry.