Distinct Modulation of I h by Synaptic Potentiation in Excitatory and Inhibitory Neurons.

IF 2.7 3区 医学 Q3 NEUROSCIENCES
eNeuro Pub Date : 2024-11-13 Print Date: 2024-11-01 DOI:10.1523/ENEURO.0185-24.2024
Lotte J Herstel, Corette J Wierenga
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Abstract

Selective modifications in the expression or function of dendritic ion channels regulate the propagation of synaptic inputs and determine the intrinsic excitability of a neuron. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels open upon membrane hyperpolarization and conduct a depolarizing inward current (I h). HCN channels are enriched in the dendrites of hippocampal pyramidal neurons where they regulate the integration of synaptic inputs. Synaptic plasticity can bidirectionally modify dendritic HCN channels in excitatory neurons depending on the strength of synaptic potentiation. In inhibitory neurons, however, the dendritic expression and modulation of HCN channels are largely unknown. In this study, we systematically compared the modulation of I h by synaptic potentiation in hippocampal CA1 pyramidal neurons and stratum radiatum (sRad) interneurons in mouse organotypic cultures. I h properties were similar in inhibitory and excitatory neurons and contributed to resting membrane potential and action potential firing. We found that in sRad interneurons, HCN channels were downregulated after synaptic plasticity, irrespective of the strength of synaptic potentiation. This suggests differential regulation of I h in excitatory and inhibitory neurons, possibly signifying their distinct role in network activity.

兴奋性神经元和抑制性神经元突触电位对 Ih 的不同调节作用
树突离子通道表达或功能的选择性改变可调节突触输入的传播,并决定神经元的内在兴奋性。超极化激活的环核苷酸门控(HCN)通道在膜超极化时开启,并传导去极化内向电流(Ih)。HCN 通道大量存在于海马锥体神经元的树突中,它们调节突触输入的整合。突触可塑性可双向改变兴奋性神经元树突的 HCN 通道,这取决于突触电位的强度。然而,在抑制性神经元中,树突HCN通道的表达和调节在很大程度上是未知的。在这项研究中,我们在小鼠器官型培养物中系统比较了突触电位对海马 CA1 锥体神经元和放射层(sRad)中间神经元中 Ih 的调节作用。抑制性神经元和兴奋性神经元的 Ih 特性相似,都有助于静息膜电位和动作电位点燃。我们发现,在 sRad 中间神经元中,HCN 通道在突触可塑性后被下调,与突触电位的强度无关。这表明兴奋性神经元和抑制性神经元对 Ih 的调控存在差异,这可能意味着它们在网络活动中扮演着不同的角色。学习反映了神经元回路中信息处理方式的改变,这种改变通过突触连接的变化和神经元内在兴奋性的改变而发生。在这里,我们研究了突触变化如何影响 HCN 通道的特性,HCN 通道是内在兴奋性的重要离子通道。我们发现,强突触电位会导致 CA1 锥体神经元和 sRad 中间神经元的 HCN 通道发生相反的变化。我们推测这反映了它们在 CA1 网络中的不同作用。锥体神经元 HCN 通道的上调导致其兴奋性降低,从而限制了整个网络的兴奋。与此相反,sRad 中间神经元显示出 Ih 的下调,因此在强突触激活后其兴奋性增加,这将加强前馈抑制并使活动模式更加清晰。
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来源期刊
eNeuro
eNeuro Neuroscience-General Neuroscience
CiteScore
5.00
自引率
2.90%
发文量
486
审稿时长
16 weeks
期刊介绍: An open-access journal from the Society for Neuroscience, eNeuro publishes high-quality, broad-based, peer-reviewed research focused solely on the field of neuroscience. eNeuro embodies an emerging scientific vision that offers a new experience for authors and readers, all in support of the Society’s mission to advance understanding of the brain and nervous system.
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