In the central nervous system, hyperpolarization-activated, cyclic nucleotide-gated (HCN1–4) channels have been implicated in neuronal excitability and synaptic transmission. It has been reported that HCN channels are expressed in the spinal cord, but knowledge about their physiological roles, as well as their distribution profiles, appear to be limited. We generated a transgenic mouse in which the expression of HCN4 can be reversibly knocked down using a genetic tetracycline-dependent switch and conducted genetically validated immunohistochemistry for HCN4. We found that the somata of HCN4-immunoreactive (IR) cells were largely restricted to the ventral part of the inner lamina II and lamina III. Many of these cells were either parvalbumin- or protein kinase Cγ (PKCγ)-IR. By using two different mouse strains in which reporters are expressed only in inhibitory neurons, we determined that the vast majority of HCN4-IR cells were excitatory neurons. Mechanical and thermal noxious stimulation did not induce c-Fos expression in HCN4-IR cells. PKCγ-neurons in this area are known to play a pivotal role in the polysynaptic pathway between tactile afferents and nociceptive projection cells that contributes to tactile allodynia. Therefore, pharmacological and/or genetic manipulations of HCN4-expressing neurons may provide a novel therapeutic strategy for the pain relief of tactile allodynia.

中文翻译：

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起搏器通道HCN4在小鼠脊髓背角的兴奋性神经元中的表达。

在中枢神经系统中，超极化激活的环状核苷酸门控（HCN1-4）通道与神经元兴奋性和突触传递有关。据报道，HCN通道在脊髓中表达，但是关于它们的生理作用以及它们的分布特征的知识似乎是有限的。我们生成了一个转基因小鼠，其中可以使用基因四环素依赖性开关可逆地敲低HCN4的表达，并进行了基因验证的HCN4免疫组化。我们发现HCN4免疫反应（IR）细胞的躯体主要局限于内部层板II和层板III的腹侧部分。这些细胞中有许多是小白蛋白或蛋白激酶Cγ（PKCγ）-IR。通过使用两种仅在抑制性神经元中表达报告基因的小鼠品系，我们确定绝大多数HCN4-IR细胞为兴奋性神经元。机械和热有害刺激未诱导HCN4-IR细胞中c-Fos表达。已知该区域中的PKCγ-神经元在触觉传入和伤害性投射细胞之间的多突触途径中起关键作用，而突触途径有助于触觉异常性疼痛。因此，表达HCN4的神经元的药理和/或遗传操作可为减轻触觉性异常性疼痛提供新的治疗策略。已知该区域中的PKCγ-神经元在触觉传入和伤害性投射细胞之间的多突触途径中起关键作用，而突触途径有助于触觉异常性疼痛。因此，表达HCN4的神经元的药理和/或遗传操作可为减轻触觉性异常性疼痛提供新的治疗策略。已知该区域中的PKCγ-神经元在触觉传入和伤害性投射细胞之间的多突触途径中起关键作用，而突触途径有助于触觉异常性疼痛。因此，表达HCN4的神经元的药理和/或遗传操作可为减轻触觉性异常性疼痛提供新的治疗策略。