Raphe serotonin neurons are not homogenous: electrophysiological, morphological and neurochemical evidence.
Raphe serotonin neurons are not homogenous: electrophysiological, morphological and neurochemical evidence.
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DOI：
10.1016/j.neuropharm.2011.04.008
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发表时间：
2011-09
影响因子：
4.7
通讯作者：
Beck SG
中科院分区：
文献类型：
--
作者：
Calizo LH;Akanwa A;Ma X;Pan YZ;Lemos JC;Craige C;Heemstra LA;Beck SG
正中核（MR）和中缝背核（DR）含有大部分投射到边缘前脑区域的5-羟色胺（5-HT，5-羟色胺）神经元，在调节稳态功能中很重要，并与情绪障碍和精神分裂症的病因学和治疗有关。中缝核内和到中缝核的主要突触输入是谷氨酸能和GABA能。DR被划分为三个子字段，即，腹内侧（vmDR）、侧翼（lwDR）和背内侧（dmDR）。我们以前的工作表明，5-HT神经元的细胞特性和5-HT 1A和5-HT 1B受体介导的反应在vmDR和MR的幅度是不一样的。我们将这些观察结果扩展到5-HT和非5-HT神经元中所有四个中缝亚区的电生理特性。用免疫组织化学方法观察海马和γ-氨基丁酸（GABA）能神经元胞体和神经末梢的分布，并对5-羟色胺（5-HT）神经元进行形态学观察。虽然5-HT神经元具有相似的生理特性，重要的差异存在的子字段。非5-HT神经元与5-HT神经元难以区分。GABA能神经元分布于中缝核的各个部位，通常位于缺乏5-HT能神经元的区域。虽然GABA能突触神经支配在整个中缝中是密集的（GABA转运体GAT 1和GAT 3的免疫组织化学分析），但它们的分布不同。谷氨酸神经元，所定义的vGlut 3抗体，混杂和共定位与5-HT神经元内的所有中缝亚。最后，5-HT神经元的树突乔木是不同的亚字段之间。以前的研究认为5-HT神经元是一个同质的群体。我们的数据支持一个模型的中缝作为一个地区组成的功能不同的亚群的5-HT和非5-HT神经元，部分划定的子域。了解相互作用的细胞特性的神经元与它们的形态，GABA和谷氨酸神经元的局部分布和它们的突触输入，揭示了一个更复杂和异质性的中缝。这些结果提供了一个重要的基础，了解特定的子字段如何调节行为，并确定哪些方面的电路被改变的心理障碍的病因。
The median (MR) and dorsal raphe (DR) nuclei contain the majority of the 5-hydroxytryptamine (5-HT, serotonin) neurons that project to limbic forebrain regions, are important in regulating homeostatic functions and are implicated in the etiology and treatment of mood disorders and schizophrenia. The primary synaptic inputs within and to the raphe are glutamatergic and GABAergic. The DR is divided into three subfields, i.e., ventromedial (vmDR), lateral wings (lwDR) and dorsomedial (dmDR). Our previous work shows that cell characteristics of 5-HT neurons and the magnitude of the 5-HT1A and 5-HT1B receptor-mediated responses in the vmDR and MR are not the same. We extend these observations to examine the electrophysiological properties across all four raphe subfields in both 5-HT and non-5-HT neurons. The neurochemical topography of glutamatergic and GABAergic cell bodies and nerve terminals were identified using immunohistochemistry and the morphology of the 5-HT neurons was measured. Although 5-HT neurons possessed similar physiological properties, important differences existed between subfields. Non-5-HT neurons were indistinguishable from 5-HT neurons. GABA neurons were distributed throughout the raphe, usually in areas devoid of 5-HT neurons. Although GABAergic synaptic innervation was dense throughout the raphe (immunohistochemical analysis of the GABA transporters GAT1 and GAT3), their distributions differed. Glutamate neurons, as defined by vGlut3 antibodies, were intermixed and co-localized with 5-HT neurons within all raphe subfields. Finally, the dendritic arbor of the 5-HT neurons was distinct between subfields. Previous studies regard 5-HT neurons as a homogenous population. Our data support a model of the raphe as an area composed of functionally distinct subpopulations of 5-HT and non-5-HT neurons, in part delineated by subfield. Understanding the interaction of the cell properties of the neurons in concert with their morphology, local distribution of GABA and glutamate neurons and their synaptic input, reveals a more complicated and heterogeneous raphe. These results provide an important foundation for understanding how specific subfields modulate behavior and for defining which aspects of the circuitry are altered during the etiology of psychological disorders.