Homeostatic Recovery of Embryonic Spinal Activity Initiated by Compensatory Changes in Resting Membrane Potential

• Type of Material: Article
• Authors: Carlos Gonzalez Islas, Emory University; Miguel Angel Garcia-Bereguiain, Universidad de Las Americas; Peter Wenner, Emory University
• Language: English
• Date: 2020-07-07
• Publisher: Society for Neuroscience
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Gonzalez-Islas et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1523/ENEURO.0526-19.2020
• Title of Journal or Parent Work: eNeuro
• Volume: 7
• Issue: 4
• Grant/Funding Information: This work was supported by the National Institute of Neurological Disorders and Stroke Grant R01NS065992 (to P.W.). MAGB was recipient of a fellowship from INEDITA (SENESCYT), Ecuador.
• Keywords: synpatic scaling; resting membrane potential; homeostatic; intrinsic plasticity; threshold voltage; Na K ATPase
• Research Categories: Biology, Neuroscience; Biology, Cell

Abstract

When baseline activity in a neuronal network is modified by external challenges, a set of mechanisms is prompted to homeostatically restore activity levels. These homeostatic mechanisms are thought to be profoundly important in the maturation of the network. It has been shown that blockade of either excitatory GABAergic or glutamatergic transmission in the living chick embryo transiently blocks the movements generated by spontaneous network activity (SNA) in the spinal cord. However, the embryonic movements then begin to recover by 2 h and are completely restored by 12 h of persistent receptor blockade. It remains unclear what mechanisms mediate this early recovery (first hours) after neurotransmitter blockade, or even if the same mechanisms are triggered following GABAergic and glutamatergic antagonists. Here we find two distinct mechanisms that could underlie this homeostatic recovery. First, we see a highly robust compensatory mechanism observed shortly after neurotransmitter receptor blockade. In the first 2 h of GABAergic or glutamatergic blockade in vitro, there was a clear depolarization of resting membrane potential (RMP) in both motoneurons and interneurons. These changes reduced threshold current and were observed in the continued presence of the antagonist. Therefore, it appears that fast changes in RMP represent a key fast homeostatic mechanism for the maintenance of network activity. Second, we see a less consistent compensatory change in the absolute threshold voltage in the first several hours of in vitro and in vivo neurotransmitter blockade. These mechanisms likely contribute to the homeostatic recovery of embryonic movements following neurotransmitter blockade.