Functional and developmental identification of a molecular subtype of brain serotonergic neuron specialized to regulate breathing dynamics.
Functional and developmental identification of a molecular subtype of brain serotonergic neuron specialized to regulate breathing dynamics.
复制标题
DOI：
10.1016/j.celrep.2014.11.027
复制
发表时间：
2014-12-24
期刊：
影响因子：
8.8
通讯作者：
Dymecki SM
中科院分区：
文献类型：
--
作者：
Brust RD;Corcoran AE;Richerson GB;Nattie E;Dymecki SM
血清素能神经元调节从攻击性和焦虑到呼吸和体温调节的行为和生理反应。涉及血清素 (5HT) 失调的疾病种类繁多且数量众多。我们假设这种功能广度部分源自 5HT 神经元不同亚型的发育决定的子结构，每个亚型专门调节特定行为。我们发现，通过在化学遗传学上一一操纵发育定义的亚组，Egr2-Pet1 亚组专门用于驱动通气增加，以应对二氧化碳升高和酸中毒。此外，这种亚型表现出内在的化学敏感性和模式特异性预测——高碳酸血症性酸中毒期间放电增加，并分别选择性地投射到呼吸化学感应但不投射到运动中枢。这些发现表明，呼吸化学反射的血清素调节是由 5HT 神经元的特殊分子亚型介导的，该神经元具有发育过程中指定的独特生理学、生物物理和方法学特性，并证明血清素能系统包含有助于其集体功能广度的专门模块。
Serotonergic neurons modulate behavioral and physiological responses from aggression and anxiety to breathing and thermoregulation. Disorders involving serotonin (5HT) dysregulation are commensurately heterogeneous and numerous. We hypothesized that this breadth in functionality derives in part from a developmentally determined substructure of distinct subtypes of 5HT neurons each specialized to modulate specific behaviors. We find, by manipulating developmentally defined subgroups one-by-one chemogenetically, that the Egr2-Pet1 subgroup is specialized to drive increased ventilation in response to carbon dioxide elevation and acidosis. Further, this subtype exhibits intrinsic chemosensitivity and modality-specific projections – increasing firing during hypercapnic acidosis and selectively projecting to respiratory chemosensory but not motor centers, respectively. These findings show that serotonergic regulation of the respiratory chemoreflex is mediated by a specialized molecular subtype of 5HT neuron harboring unique physiological, biophysical, and hodological properties specified developmentally, and demonstrate that the serotonergic system contains specialized modules contributing to its collective functional breadth.
登录
查看更多内容
DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
影响因子：
3.7
作者：
Baccini G;Mlinar B;Audero E;Gross CT;Corradetti R
通讯作者：
Corradetti R
DOI：
10.1111/j.1460-9568.2011.07936.x
发表时间：
2012-01
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Bang SJ;Jensen P;Dymecki SM;Commons KG
通讯作者：
Commons KG
影响因子：
2.5
作者：
Iceman, Kimberly E.;Richerson, George B.;Harris, Michael B.
通讯作者：
Harris, Michael B.
DOI：
10.1073/pnas.0906593106
发表时间：
2009-11-10
影响因子：
11.1
作者：
Guettier, Jean-Marc;Gautam, Dinesh;Wess, Juergen
通讯作者：
Wess, Juergen