Postnatal maturation of spinal dynorphin circuits and their role in somatosensation.

Postnatal maturation of spinal dynorphin circuits and their role in somatosensation.
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DOI:
10.1097/j.pain.0000000000001884
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发表时间:
2020-08
期刊:
影响因子:
7.4
通讯作者:
Baccei ML
Baccei ML
中科院分区:
医学1区
文献类型:
--
作者:
Brewer CL;Styczynski LM;Serafin EK;Baccei ML

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抑制性中间神经元在成人脊髓背角(DH)可以神经化学分类为亚群,调节不同的体感方式。虽然抑制网络在啮齿动物DH经历了戏剧性的重塑在生命的第一个星期,很少有人知道的成熟的GABA能中间神经元的类,或他们的角色在躯体感觉的转变在发展过程中。我们研究了小鼠DH中强啡肽原(DYN)谱系神经元的连接和功能的年龄依赖性变化,这些神经元在成年期抑制机械感觉和瘙痒。在体外膜片钳记录显示,初级传入驱动DYN中间神经元的发展增加,从独家C-纤维单突触输入混合A-纤维和C-纤维神经支配的过渡。虽然大多数成年DYN中间神经元表现出紧张性放电,从他们的抑制表型预期,新生儿和青少年DYN细胞主要被归类为阶段性或单穗。重要的是,我们还发现,大多数的抑制性突触前末梢接触第一层脊髓臂旁投射神经元(PN)起源于DYN神经元。此外,从DYN中间神经元到PN的抑制性突触输入在新生儿期较弱,可能反映了与成人相比,GABA能末梢的数量较少,GABA释放的可能性降低。最后,脊髓DYN interneurons衰减机械敏感性在整个发展,但这个人口抑制急性非组胺能瘙痒只有在成年期。总的来说,这些研究结果表明,脊髓“门”控制感觉传递到大脑可能出现在一个模态选择性的方式在生命早期由于产后调整抑制性突触回路内的DH。
Inhibitory interneurons in the adult spinal dorsal horn (DH) can be neurochemically classified into subpopulations that regulate distinct somatosensory modalities. Although inhibitory networks in the rodent DH undergo dramatic remodeling over the first weeks of life, little is known about the maturation of identified classes of GABAergic interneurons, or whether their role in somatosensation shifts during development. We investigated age-dependent changes in the connectivity and function of prodynorphin (DYN)-lineage neurons in the mouse DH that suppress mechanosensation and itch during adulthood. In vitro patch clamp recordings revealed a developmental increase in primary afferent drive to DYN interneurons and a transition from exclusive C-fiber monosynaptic input to mixed A-fiber and C-fiber innervation. Although most adult DYN interneurons exhibited tonic firing as expected from their inhibitory phenotype, neonatal and adolescent DYN cells were predominantly classified as phasic or single-spiking. Importantly, we also found that most of the inhibitory presynaptic terminals contacting lamina I spinoparabrachial projection neurons (PNs) originate from DYN neurons. Furthermore, inhibitory synaptic input from DYN interneurons onto PNs was weaker during the neonatal period, likely reflecting a lower number of GABAergic terminals and a reduced probability of GABA release compared to adults. Finally, spinal DYN interneurons attenuated mechanical sensitivity throughout development, but this population dampened acute nonhistaminergic itch only during adulthood. Collectively, these findings suggest that the spinal “gates” controlling sensory transmission to the brain may emerge in a modality-selective manner during early life due to the postnatal tuning of inhibitory synaptic circuits within the DH.
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