Neuropeptide Modulation Increases Dendritic Electrical Spread to Restore Neuronal Activity Disrupted by Temperature
Neuropeptide Modulation Increases Dendritic Electrical Spread to Restore Neuronal Activity Disrupted by Temperature
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DOI：
10.1523/jneurosci.0101-21.2021
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发表时间：
2021-09-08
影响因子：
5.3
通讯作者：
Stein, Wolfgang
中科院分区：
文献类型：
--
作者：
DeMaegd, Margaret L.;Stein, Wolfgang
多肽神经调节被认为可以保护神经元活性不受急性温度变化的影响，否则会导致运动控制的丧失或重要行为的失败。然而，神经肽激发的支持温度强健活动的细胞作用仍不清楚。在这里，我们发现，多肽神经调制通过抵消膜分流和增加树突电扩散来恢复温度受损的中枢模式生成器(CPG)神经元的节律性爆发。我们发现，温度的急剧上升减少了甲壳类胃磨机CPG的尖峰产生并中断了正在进行的节律性运动活动。神经释放和外源性应用P物质相关肽--北极癌速激肽相关肽Ia(CabTRP Ia)可恢复节律活动。加温可显著降低胃粘膜CPG主要神经元的膜电阻和树突信号的分流。结合钙荧光成像和电生理学，我们观察到，随着系统的升温，突触后电位和逆行动作电位在树突神经桩内传播的距离较小。在CabTrp Ia存在下，膜分流减少，突触后电位和逆行动作电位传播更远。在高温下，CabTrp Ia恢复了树突的电扩散，或将其延伸到低温下。使用动态钳位选择性地引入CabTrp Ia电导表明，CabTrp Ia电压依赖的电导足以恢复节律性爆发。我们的发现表明，P物质相关的神经肽可以促进树突电扩散，以在受到干扰时维持神经元的活动，并揭示了神经肽活动的关键神经生理成分，这些神经生理成分支持在温度受损的条件下产生模式。意义陈述体温的变化可能会对生物体的健康产生有害的后果。神经活动的温度依赖性变化如果影响生命行为，可能会特别危险。了解温度变化如何扰乱神经元的活动并确定如何改善这种影响是至关重要的。我们对克鲁斯塔回路的研究表明，变暖通过增加膜分流和减少关键回路神经元中的树突电扩散来扰乱节律性神经元的活动。通过它激活的离子电导，P物质相关的多肽调节恢复了电传播，并抵消了不利的温度对节律活动的影响。由于神经肽通常与在扰动期间维持神经元活动有关，我们的结果提供了一个有希望的机制来支持温度强健的活动。
Peptide neuromodulation has been implicated to shield neuronal activity from acute temperature changes that can otherwise lead to loss of motor control or failure of vital behaviors. However, the cellular actions neuropeptides elicit to support tem-perature-robust activity remain unknown. Here, we find that peptide neuromodulation restores rhythmic bursting in temper-ature-compromised central pattern generator (CPG) neurons by counteracting membrane shunt and increasing dendritic electrical spread. We show that acutely rising temperatures reduced spike generation and interrupted ongoing rhythmic motor activity in the crustacean gastric mill CPG. Neuronal release and extrinsic application of Cancer borealis tachykinin-related peptide Ia (CabTRP Ia), a substance-P-related peptide, restored rhythmic activity. Warming led to a significant decrease in membrane resistance and a shunting of the dendritic signals in the main gastric mill CPG neuron. Using a combi-nation of fluorescent calcium imaging and electrophysiology, we observed that postsynaptic potentials and antidromic action potentials propagated less far within the dendritic neuropil as the system warmed. In the presence of CabTRP Ia, membrane shunt decreased and both postsynaptic potentials and antidromic action potentials propagated farther. At elevated tempera-tures, CabTRP Ia restored dendritic electrical spread or extended it beyond that at cold temperatures. Selective introduction of the CabTRP Ia conductance using a dynamic clamp demonstrated that the CabTRP Ia voltage-dependent conductance was sufficient to restore rhythmic bursting. Our findings demonstrate that a substance-P-related neuropeptide can boost dendritic electrical spread to maintain neuronal activity when perturbed and reveals key neurophysiological components of neuropep-tide actions that support pattern generation in temperature-compromised conditions. Significance Statement Changes in body temperature can have detrimental consequences for the well-being of an organism. Temperature-dependent changes in neuronal activity can be especially dangerous if they affect vital behaviors. Understanding how temperature changes disrupt neuronal activity and identifying how to ameliorate such effects is critically important. Our study of a crusta-cean circuit shows that warming disrupts rhythmic neuronal activity by increasing membrane shunt and reducing dendritic electrical spread in a key circuit neuron. Through the ionic conductance activated by it, substance-P-related peptide modula-tion restored electrical spread and counteracted the detrimental temperature effects on rhythmic activity. Because neuropepti-des are commonly implicated in sustaining neuronal activity during perturbation, our results provide a promising mechanism to support temperature-robust activity.