Descending 5-hydroxytryptamine raphe inputs repress the expression of serotonergic neurons and slow the maturation of inhibitory systems in mouse embryonic spinal cord
Descending 5-hydroxytryptamine raphe inputs repress the expression of serotonergic neurons and slow the maturation of inhibitory systems in mouse embryonic spinal cord
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DOI：
10.1523/jneurosci.22-07-02598.2002
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发表时间：
2002-04-01
影响因子：
5.3
通讯作者：
Meyrand, P
中科院分区：
文献类型：
--
作者：
Branchereau, P;Chapron, J;Meyrand, P
自发的同步节律活动是未成熟神经元网络的共同特征。虽然这些活动的机制已被广泛研究，但它们是否受调节信息的控制仍存在疑问。在这里，我们调查的作用，下行多巴胺能（5-HT）的输入从延髓到脊髓的成熟的节奏活动。我们发现，在脊髓维持，作为一个整体，在器官型文化没有髓质，自发活动的成熟是类似的，在子宫内发育的脊髓中发现。有趣的是，在没有骨髓的器官型培养物中（即，缺乏下行输入），许多脊髓内神经元表达5-HT，这与在髓质存在下培养或在子宫内成熟的脊髓不同。我们证明，这种5-HT的表达是专门依赖于5-HT纤维的情况下，并通过5-HT 1A受体的激活被抑制5-HT本身。最后，为了验证5-HT椎管内神经元的表达是否可以补偿下降的5-HT纤维的缺乏，并在自发活动的发展中发挥作用，我们在没有髓质的培养物中使用对氯苯丙氨酸甲酯阻断了5-HT的合成。令人惊讶的是，我们发现这种药物治疗并没有阻止自发活动的发展，但在研究阶段加速了椎管内抑制的成熟。总之，我们的数据表明，下行5-HT中缝输入（1）抑制脊髓5-羟色胺能神经元的表达，（2）减缓小鼠脊髓抑制系统的成熟。
Spontaneous synchronous rhythmic activities are a common feature of immature neuronal networks. Although the mechanisms underlying such activities have been studied extensively, whether they might be controlled by modulatory information remains questionable. Here, we investigated the role of descending serotonergic (5-HT) inputs from the medulla to the spinal cord in the maturation of rhythmic activity. We found that in spinal cords maintained, as a whole, in organotypic culture without the medulla, the maturation of spontaneous activity is similar to that found in spinal cords developed in utero. Interestingly, in organotypic cultures without the medulla (i.e., devoid of descending inputs), numerous intraspinal neurons expressed 5-HT, unlike in spinal cords cultivated in the presence of the medulla or matured in utero. We demonstrated that this 5-HT expression was specifically dependent on the absence of 5-HT fibers and was repressed by 5-HT itself via activation of 5-HT1A receptors. Finally, to verify whether the expression of 5-HT intraspinal neurons could compensate for the lack of descending 5-HT fibers and play a role in the development of spontaneous activity, we blocked the 5-HT synthesis using p-chlorophenylalanine methyl ester in cultures devoid of the medulla. Surprisingly, we found that this pharmacological treatment did not prevent the development of spontaneous activity but accelerated the maturation of intraspinal inhibition at the studied stages. Together, our data indicate that descending 5-HT raphe inputs (1) repress the expression of spinal serotonergic neurons and (2) slow the maturation of inhibitory systems in mouse spinal cord.