TY - JOUR T1 - Homeostatic recovery of embryonic spinal activity initiated by compensatory changes in resting membrane potential JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0526-19.2020 SP - ENEURO.0526-19.2020 AU - Carlos Gonzalez-Islas AU - Miguel Angel Garcia-Bereguiain AU - Peter Wenner Y1 - 2020/06/15 UR - http://www.eneuro.org/content/early/2020/06/15/ENEURO.0526-19.2020.abstract N2 - 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 hours and are completely restored by 12 hours 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 two hours of GABAergic or glutamatergic blockade in vitro there was a clear depolarization of resting membrane potential 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 resting membrane potential 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.Significance Homeostatic plasticity represents a set of mechanisms that act to recover cellular or network activity following a challenge and is thought to be critical for the developmental construction of the nervous system. The chick embryo afforded us the opportunity to observe the timing of homeostatic recovery of network activity following 2 distinct perturbations in a living developing system. Because of this advantage, we have identified a novel homeostatic mechanism that actually occurs as the network recovers and is therefore likely to contribute to nervous system homeostasis. We found that a depolarization of the resting membrane potential and a hyperpolarization of threshold voltage in the first hours of the perturbation enhances excitability and supports the recovery of embryonic spinal network activity. ER -