Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition.

Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition.
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DOI:
10.1126/science.1205295
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发表时间:
2011-07-29
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Dymecki SM
Dymecki SM
中科院分区:
其他
文献类型:
--
作者:
Ray RS;Corcoran AE;Brust RD;Kim JC;Richerson GB;Nattie E;Dymecki SM

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生理稳态对生物体的生存至关重要。高度反应的神经元网络参与,但组成神经元才刚刚开始被解决。为了查询处于稳态的脑多巴胺能神经元,我们使用了一种基于合成GPCR(Di)的神经元沉默工具,小鼠RC FPDi,其设计用于细胞类型特异性、配体(氯氮平-N-氧化物,CNO)诱导的和可逆的动作电位放电抑制。在小鼠窝藏DI-表达的肾上腺素能神经元,CNO管理全身注射衰减的化学反射,通常增加呼吸组织CO2升高和酸中毒。在细胞水平上,CNO抑制了CO2/酸中毒引起的放电率增加。在室温下的体温调节也被破坏后,CNO触发的Di;核心温度骤降,然后恢复。这项工作确立了多巴胺能神经元调节维持生命的呼吸和体温调节网络,并展示了一种用于映射神经元功能的非侵入性工具。
Physiological homeostasis is essential for organism survival. Highly responsive neuronal networks are involved but constituent neurons are just beginning to be resolved. To query brain serotonergic neurons in homeostasis, we used a synthetic GPCR (Di)-based neuronal silencing tool, mouse RC∷FPDi, designed for cell type-specific, ligand (clozapine-N-oxide, CNO)-inducible and reversible suppression of action potential firing. In mice harboring Di-expressing serotonergic neurons, CNO administration by systemic injection attenuated the chemoreflex that normally increases respiration in response to tissue CO2 elevation and acidosis. At the cellular level, CNO suppressed firing rate increases evoked by CO2/acidosis. Body thermoregulation at room temperature was also disrupted following CNO triggering of Di; core temperatures plummeted, then recovered. This work establishes that serotonergic neurons regulate life-sustaining respiratory and thermoregulatory networks, and demonstrates a noninvasive tool for mapping neuron function.
DOI: 10.1016/j.neuron.2009.07.010
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