School of Psychology and Neuroscience, University of St Andrews, St Marys Quad., St Andrews, Fife KY16 9AP, Scotland.
Centre for Discovery Brain Sciences, University of Edinburgh, 49 Little France Crescent, Edinburgh Bioquarter, Edinburgh EH16 4SB, Scotland.
Curr Biol. 2022 Mar 14;32(5):1038-1048.e2. doi: 10.1016/j.cub.2022.01.012. Epub 2022 Jan 31.
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.
正常情况下，由于神经元钠钾泵对细胞内钠离子的亲和力较低，只有在强烈的动作电位放电时才会发生反应。这些钠泵的募集会产生一种幅度约为 10 mV、持续时间约为 60 s 的超慢后超极化（usAHP），这会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，它以依赖于运动回合之间间隔的方式降低运动网络输出的强度和持续时间。与帮助设定和维持静息膜电位的持续激活的钠泵不同，动态钠泵被低浓度哇巴因选择性拮抗，我们发现，哇巴因可以阻断 usAHP 和 STMM。我们研究了神经调质是否可以影响动态钠泵和 STMM，重点关注 5-HT 和一氧化氮。单独应用 5-HT 对 usAHP 或 STMM 没有显著影响。然而，这是由于两种不同的 5-HT 受体亚型（5-HT7 和 5-HT2a）的同时激活，它们分别对运动系统的这两个特征具有促进和抑制作用。一氧化氮调节产生强烈的抑制作用，可以完全阻断 usAHP 并消除 STMM。使用 5-HT7 和 5-HT2a 受体的选择性阻滞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种内源性控制系统，根据最近的经验决定脊髓网络如何自我调节运动输出的强度。
