P278 Speeding-up Distinct Bursting Regimes is Mediated by Separate Coregulation Pathways
Yousif O. Shams1, Ronald L. Calabrese2, Gennady S. Cymbalyuk1,*
1Neuroscience Institute, Georgia State University, Atlanta, Georgia, 30302, USA. 2Department of Biology, Emory University, Atlanta, Georgia, 30322, USA
*E-mail: gcymbalyuk@gmail.com
Introduction Central pattern generators (CPGs) control rhythmic behaviors and adapt to behavioral demands via neuromodulation[1]. The leech heartbeat CPG includes mutually inhibitory heart interneurons (HNs) forming half-center oscillators (HCOs)[1]. Myomodulin speeds up HCO bursting by increasing h-current (Ih) and decreasingNa+/ K+pump current(IPump)[2]. These changes create a coregulation path between dysfunctional regimes[3].Along this path, a new functional regime, high-spike frequency bursting (HFB), emerges alongside low-spike frequency bursting (LFB)[4]. Separately, based on interaction ofIPumpand persistentcurrent,creating relaxation oscillator dynamics,dynamical clamp experiments also show a transition into high- frequency bursting (HFBROd)[5].
Methods
We use experimentally validated Hodgkin-Huxley-style models with Na+dynamics incorporated, which are proven effective in predicting HCO behaviors under various experimental and neuromodulatory conditions[3-6].We conduct a two-parameter sweep, maximalIPump(IPumpMax) andconductance ofIh(gh,to map the activity regimes. We investigate how neuromodulation affects the HCO cycle period of the LFB and HFB regimes, and map experimental data onto the map of regimes.
Results Under variation ofIPumpMaxandgh, HCO and single HN show a phase transition between HFB and LFB. In LFB, decreasingIPumpMaxspeeds up bursting, consistent with myomodulin neuromodulation [2,3]. In HFBROd, increasingIPumpMaxalso speeds up bursting by shortening burst duration and interburst interval in accordance with relaxation-oscillator dynamics [5]. Mapping experimental cycle period suggests that myomodulin operates along a coregulation path within LFB regime. This mapping of experimental data of cycle period reveals a quasi-orthogonal path where increasingIPumpMax speeds up bursting within HFB regime. Transition between the bursting regimes elucidates monensin effects. Monensin, aantiporter, speeds up bursting via raising intracellularconcentration ([Na+]i), thereby increasingIPump[6].
Conclusions Modeling suggests the emergence of HFB regime alongside LFB, each with distinct responses to neuromodulation. This captures a paradox of speeding up HCO bursting by either increasing or decreasingIPump. LFB and HFB regimes operate with distinct mechanisms for controlling bursting cycle period. This distinction arises from intracellulardynamics. LFB is responsive to coregulationIhof andIPump. In contrast, HFB operates with relaxation-oscillator dynamics based on[Na+]i. Our results emphasize that transitioning between LFB and HFB enhances the CPG’s robustness and flexibility, allowing for adaptive control of bursting.
Acknowledgements We acknowledge Georgia State University’s Brains and Behavior program grant to GSC. References 1.https://doi.org/10.1152/physrev.00003.2024 2.https://doi.org/10.1152/jn.00340.2005 3.https://doi.org/10.1523/JNEUROSCI.0158-21.2021 4.https://doi.org/10.3389/fncel.2024.1395026 5.https://doi.org/10.1523/ENEURO.0331-22.2023 6.https://doi.org/10.7554/eLife.19322
