Bimodal modulation of short-term motor memory via dynamic sodium pumps in a vertebrate spinal cord

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...

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Published in:Current biology Vol. 32; no. 5; pp. 1038 - 1048.e2
Main Authors: Hachoumi, Lamia, Rensner, Rebecca, Richmond, Claire, Picton, Laurence, Zhang, HongYan, Sillar, Keith T.
Format: Journal Article
Language:English
Published: England Elsevier Inc 14-03-2022
Cell Press
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Summary: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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ISSN:0960-9822
1879-0445
1879-0445
DOI:10.1016/j.cub.2022.01.012