Bimodal modulation of short-term motor memory via dynamic sodium pumps in a vertebrate spinal cord.
Bimodal modulation of short-term motor memory via dynamic sodium pumps in a vertebrate spinal cord.
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DOI：
10.1016/j.cub.2022.01.012
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发表时间：
2022-03-14
期刊：
影响因子：
9.2
通讯作者：
Sillar, Keith T.
中科院分区：
文献类型：
--
作者：
Hachoumi, Lamia;Rensner, Rebecca;Richmond, Claire;Picton, Laurence;Zhang, HongYan;Sillar, Keith T.
动态神经元Na+/K+泵通常仅响应于强烈的动作电位放电，这是由于它们对细胞内Na+的低亲和力。这些Na+泵的募集产生活动后超低后超极化（usAHP），幅度高达10 mV，持续时间为160 s，影响神经元的特性和未来的网络输出。在脊髓运动网络中，usAHP是短期运动记忆（STMM）的基础，以依赖于运动发作之间的间隔的方式降低运动网络输出的强度和持续时间。与有助于设置和维持静息膜电位的紧张性活性Na+泵相反，动态Na+泵被低浓度的哇巴因选择性地拮抗，我们发现，这阻止了usAHP和STMM。我们研究了动态Na+泵和STMM是否可以受到神经调节剂的影响，重点是5-HT和一氧化氮。单独使用5-HT对usAHP或STMM没有显着影响。然而，这是由于同时激活两种不同的5-HT受体亚型（5-HT 7和5-HT 2a），分别对运动系统的这两个特征具有相反的促进和抑制作用。一氧化氮调节发挥了有效的抑制作用，可以完全阻断usAHP和清除STMM。使用5-HT 7和5-HT 2a受体的选择性阻断剂和一氧化氮清除剂PTIO，我们进一步提供证据表明，这两种调节剂构成了一个内源性控制系统，根据最近的经验，该系统决定了脊髓网络如何自我调节运动输出的强度。脊髓运动网络中的短时记忆受动态Na+泵的控制Na+泵介导由5-HT受体和NO调节的潜在超低AHP 5-HT 7 Rs增加而5-HT 2aRs和NO降低usAHP和短时运动记忆内源性5-HT和NO调节usAHP和短时运动记忆钠泵介导脊髓运动网络中的活动依赖性短时记忆。Hachoumi等人显示这种记忆和潜在的超低后超极化是由内源性NO和5-HT调节的。5-HT 7受体增强，而NO和5-HT 2a受体减少钠泵控制的运动活动。
Dynamic neuronal Na+/K+ pumps normally only respond to intense action potential firing owing to their low affinity for intracellular Na+. Recruitment of these Na+ pumps produces a post-activity ultraslow afterhyperpolarization (usAHP) up to ∼10 mV in amplitude and ∼60 s in duration, which influences neuronal properties and future network output. In spinal motor networks, the usAHP underlies short-term motor memory (STMM), reducing the intensity and duration of locomotor network output in a manner dependent on the interval between locomotor bouts. In contrast to tonically active Na+ pumps that help set and maintain the resting membrane potential, dynamic Na+ pumps are selectively antagonized by low concentrations of ouabain, which, we show, blocks both the usAHP and STMM. We examined whether dynamic Na+ pumps and STMM can be influenced by neuromodulators, focusing on 5-HT and nitric oxide. Bath-applied 5-HT alone had no significant effect on the usAHP or STMM. However, this is due to the simultaneous activation of two distinct 5-HT receptor subtypes (5-HT7 and 5-HT2a) that have opposing facilitatory and suppressive influences, respectively, on these two features of the locomotor system. Nitric oxide modulation exerts a potent inhibitory effect that can completely block the usAHP and erase STMM. Using selective blockers of 5-HT7 and 5-HT2a receptors and a nitric oxide scavenger, PTIO, we further provide evidence that the two modulators constitute an endogenous control system that determines how the spinal network self-regulates the intensity of locomotor output in light of recent past experience. Short-term memory in a spinal locomotor network is controlled by dynamic Na+ pumps Na+ pumps mediate an underlying ultraslow AHP modulated by 5-HT receptors and NO 5-HT7Rs increase and 5-HT2aRs and NO decrease the usAHP and short-term motor memory Endogenous 5-HT and NO regulate the usAHP and short-term motor memory Sodium pumps mediate activity-dependent short-term memory in spinal locomotor networks. Hachoumi et al. show this memory and an underlying ultraslow afterhyperpolarization are modulated by endogenous NO and 5-HT. 5-HT7 receptors enhance, while NO and 5-HT2a receptors reduce sodium pump control of locomotor activity.
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