Ion Channels; Animals; Pylorus; Temperature; Brachyura; Neurons; Biophysics
Abstract :
[en] Neuronal activity depends on ion channels and biophysical processes that are strongly and differentially sensitive to physical variables such as temperature and pH. Nonetheless, neuronal oscillators can be surprisingly resilient to perturbations in these variables. We study a three-neuron pacemaker ensemble that drives the pyloric rhythm of the crab, Cancer borealis. These crabs routinely experience a number of global perturbations, including changes in temperature and pH. Although pyloric oscillations are robust to such changes, for sufficiently large deviations the rhythm reversibly breaks down. As temperature increases beyond a tipping point, oscillators transition to silence. Acidic pH deviations also show tipping points, with a reliable transition first to tonic spiking, then to silence. Surprisingly, robustness to perturbations in pH only moderately affects temperature robustness. Consistent with high animal-to-animal variability in biophysical circuit parameters, tipping points in temperature and pH vary across animals. However, the ordering and discrete classes of transitions at critical points are conserved. This implies that qualitative oscillator dynamics are preserved across animals despite high quantitative parameter variability. A universal model of bursting dynamics predicts the existence of these transition types and the order in which they occur.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Ratliff, Jacob; Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York
Franci, Alessio ; Université de Liège - ULiège > Département d'électricité, électronique et informatique (Institut Montefiore) > Brain-Inspired Computing ; Department of Mathematics, National Autonomous University of Mexico, Mexico City, Mexico
NIH - National Institutes of Health [US-MD] [US-MD] ERC - European Research Council [BE]
Funding text :
We acknowledge Anatoly Rinberg for his contribution to this work in performing experiments that were preliminary to the study here. We also thank Jessica Haley for sharing experimental results that informed the design of these experiments. This work is funded by NIH Grants R35 NS 097343 and MH 46742 to E.M. and by ERC Grant StG 2016 716643 FLEXNEURO to T.O.L.
Obara, M., Szeliga, M., Albrecht, J., Regulation of pH in the mammalian central nervous system under normal and pathological conditions: facts and hypotheses. Neurochem. Int 52 (2008), 905–919.
Marder, E., Haddad, S.A., et al., Kispersky, T., How can motor systems retain performance over a wide temperature range? Lessons from the crustacean stomatogastric nervous system. J. Comp. Physiol. A Neuroethol. Sens. Neural Behav. Physiol 201 (2015), 851–856.
Pequeux, A., Osmotic regulation in crustaceans. J. Crustac. Biol 15 (1995), 1–60.
Robertson, R.M., Money, T.G., Temperature and neuronal circuit function: compensation, tuning and tolerance. Curr. Opin. Neurobiol 22 (2012), 724–734.
Haddad, S.A., Marder, E., Circuit robustness to temperature perturbation is altered by neuromodulators. Neuron 100 (2018), 609–623.e3.
Garrity, P.A., Goodman, M.B., et al., Sengupta, P., Running hot and cold: behavioral strategies, neural circuits, and the molecular machinery for thermotaxis in C. elegans and Drosophila. Genes Dev 24 (2010), 2365–2382.
Alonso, L.M., Marder, E., Temperature compensation in a small rhythmic circuit. eLife, 9, 2020, e55470.
Roemschied, F.A., Eberhard, M.J., et al., Schreiber, S., Cell-intrinsic mechanisms of temperature compensation in a grasshopper sensory receptor neuron. eLife, 3, 2014, e02078.
Tang, L.S., Taylor, A.L., et al., Marder, E., Robustness of a rhythmic circuit to short- and long-term temperature changes. J. Neurosci 32 (2012), 10075–10085.
Tang, L.S., Goeritz, M.L., et al., Marder, E., Precise temperature compensation of phase in a rhythmic motor pattern. PLoS Biol, 8, 2010, e1000469.
Soofi, W., Goeritz, M.L., et al., Stein, W., Phase maintenance in a rhythmic motor pattern during temperature changes in vivo. J. Neurophysiol 111 (2014), 2603–2613.
Rinberg, A., Taylor, A.L., Marder, E., The effects of temperature on the stability of a neuronal oscillator. PLoS Comput. Biol, 9, 2013, e1002857.
Caplan, J.S., Williams, A.H., Marder, E., Many parameter sets in a multicompartment model oscillator are robust to temperature perturbations. J. Neurosci 34 (2014), 4963–4975.
O'Leary, T., Marder, E., Temperature-robust neural function from activity-dependent ion channel regulation. Curr. Biol 26 (2016), 2935–2941.
Schulz, D.J., Goaillard, J.M., Marder, E.E., Quantitative expression profiling of identified neurons reveals cell-specific constraints on highly variable levels of gene expression. Proc. Natl. Acad. Sci. USA 104 (2007), 13187–13191.
Schulz, D.J., Goaillard, J.M., Marder, E., Variable channel expression in identified single and electrically coupled neurons in different animals. Nat. Neurosci 9 (2006), 356–362.
Temporal, S., Lett, K.M., Schulz, D.J., Activity-dependent feedback regulates correlated ion channel mRNA levels in single identified motor neurons. Curr. Biol 24 (2014), 1899–1904.
Shruti, S., Schulz, D.J., et al., Marder, E., Electrical coupling and innexin expression in the stomatogastric ganglion of the crab Cancer borealis. J. Neurophysiol 112 (2014), 2946–2958.
Drion, G., Franci, A., Dethier, J., Sepulchre, R., Dynamic input conductances shape neuronal spiking. eNeuro, 2, 2015 ENEURO.0031-14.2015.
Franci, A., Drion, G., et al., Sepulchre, R., A balance equation determines a switch in neuronal excitability. PLoS Comput. Biol, 9, 2013, e1003040.
Franci, A., Drion, G., Sepulchre, R., Modeling the modulation of neuronal bursting: a singularity theory approach. SIAM J. Appl. Dyn. Syst 13 (2014), 798–829.
Tombaugh, G.C., Somjen, G.G., Effects of extracellular pH on voltage-gated Na+, K+ and Ca2+ currents in isolated rat CA1 neurons. J. Physiol 493 (1996), 719–732.
Church, J., Baxter, K.A., McLarnon, J.G., pH modulation of Ca2+ responses and a Ca2+-dependent K+ channel in cultured rat hippocampal neurones. J. Physiol 511 (1998), 119–132.
Xiong, Z.-Q., Stringer, J.L., Extracellular pH responses in CA1 and the dentate gyrus during electrical stimulation, seizure discharges, and spreading depression. J. Neurophysiol 83 (2000), 3519–3524.
Cook, D.L., Ikeuchi, M., Fujimoto, W.Y., Lowering of pHi inhibits Ca2+-activated K+ channels in pancreatic B-cells. Nature 311 (1984), 269–271.
Hille, B., Ion Channels of Excitable Membranes. Third Edition, 2001, Sinauer Associates, Sunderland, MA.
Golowasch, J., Deitmer, J.W., pH regulation in the stomatogastric ganglion of the crab Cancer pagurus. J. Comp. Physiol. A 172 (1993), 573–581.
Truchot, J.P., Temperature and acid-base regulation in the shore crab Carcinus maenas (L.). Respir. Physiol 17 (1973), 11–20.
Sartoris, F.-J., Pörtner, H.-O., Temperature dependence of ionic and acid-base regulation in boreal and arctic Crangon crangon and Pandalus borealis. J. Exp. Mar. Biol. Ecol 211 (1997), 69–83.
Whiteley, N., Physiological and ecological responses of crustaceans to ocean acidification. Mar. Ecol. Prog. Ser 430 (2011), 257–271.
Marder, E., Eisen, J.S., Transmitter identification of pyloric neurons: electrically coupled neurons use different transmitters. J. Neurophysiol 51 (1984), 1345–1361.
Haley, J.A., Hampton, D., Marder, E., Two central pattern generators from the crab, Cancer borealis, respond robustly and differentially to extreme extracellular pH. eLife, 7, 2018, e41877.
Doering, C.J., McRory, J.E., Effects of extracellular pH on neuronal calcium channel activation. Neuroscience 146 (2007), 1032–1043.
Veraart, A.J., Faassen, E.J., et al., Scheffer, M., Recovery rates reflect distance to a tipping point in a living system. Nature 481 (2011), 357–359.
Scheffer, M., Carpenter, S.R., et al., Vandermeer, J., Anticipating critical transitions. Science 338 (2012), 344–348.
Kandel, D., Domany, E., et al., Loh, E. Jr., Simulations without critical slowing down. Phys. Rev. Lett 60 (1988), 1591–1594.
Chisholm, R.A., Filotas, E., Critical slowing down as an indicator of transitions in two-species models. J. Theor. Biol 257 (2009), 142–149.
Drion, G., O'Leary, T., Marder, E., Ion channel degeneracy enables robust and tunable neuronal firing rates. Proc. Natl. Acad. Sci. USA 112 (2015), E5361–E5370.
Golowasch, J., Bose, A., et al., Nadim, F., A balance of outward and linear inward ionic currents is required for generation of slow-wave oscillations. J. Neurophysiol 118 (2017), 1092–1104.
Gray, M., Golowasch, J., Voltage dependence of a neuromodulator-activated ionic current. eNeuro, 3, 2016 ENEURO.0038-16.2016.
Rodriguez, J.C., Blitz, D.M., Nusbaum, M.P., Convergent rhythm generation from divergent cellular mechanisms. J. Neurosci 33 (2013), 18047–18064.
Golowasch, J., Marder, E., Proctolin activates an inward current whose voltage dependence is modified by extracellular Ca2+. J. Neurosci 12 (1992), 810–817.
Golowasch, J., Marder, E., Ionic currents of the lateral pyloric neuron of the stomatogastric ganglion of the crab. J. Neurophysiol 67 (1992), 318–331.
Guckenheimer, J., Holmes, P., Nonlinear Oscillations, Dynamical Systems, and Bifurcations of Vector Fields. 2013, Springer Science and Business Media, New York.
Sobie, E.A., Parameter sensitivity analysis in electrophysiological models using multivariable regression. Biophys. J 96 (2009), 1264–1274.
Tobin, A.E., Calabrese, R.L., Endogenous and half-center bursting in morphologically inspired models of leech heart interneurons. J. Neurophysiol 96 (2006), 2089–2106.
Canavier, C.C., Clark, J.W., Byrne, J.H., Simulation of the bursting activity of neuron R15 in Aplysia: role of ionic currents, calcium balance, and modulatory transmitters. J. Neurophysiol 66 (1991), 2107–2124.
Guckenheimer, J., Gueron, S., Harris-Warrick, R.M., Mapping the dynamics of a bursting neuron. Philos. Trans. R. Soc. Lond. B Biol. Sci 341 (1993), 345–359.
Alonso, L.M., Marder, E., Visualization of currents in neural models with similar behavior and different conductance densities. eLife, 8, 2019, e42722.
Goaillard, J.-M., Taylor, A.L., et al., Marder, E., Functional consequences of animal-to-animal variation in circuit parameters. Nat. Neurosci 12 (2009), 1424–1430.
Grashow, R., Brookings, T., Marder, E., Compensation for variable intrinsic neuronal excitability by circuit-synaptic interactions. J. Neurosci 30 (2010), 9145–9156.
Taylor, A.L., Goaillard, J.M., Marder, E., How multiple conductances determine electrophysiological properties in a multicompartment model. J. Neurosci 29 (2009), 5573–5586.
O'Leary, T., Williams, A.H., et al., Marder, E., Cell types, network homeostasis, and pathological compensation from a biologically plausible ion channel expression model. Neuron 82 (2014), 809–821.
O'Leary, T., Williams, A.H., et al., Marder, E., Correlations in ion channel expression emerge from homeostatic tuning rules. Proc. Natl. Acad. Sci. USA 110 (2013), E2645–E2654.
O'Leary, T., Homeostasis, failure of homeostasis and degenerate ion channel regulation. Curr. Opin. Physiol 2 (2018), 129–138.
