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Convergent neuromodulation onto a network neuron can have divergent effects at the network level

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Abstract

Different neuromodulators often target the same ion channel. When such modulators act on different neuron types, this convergent action can enable a rhythmic network to produce distinct outputs. Less clear are the functional consequences when two neuromodulators influence the same ion channel in the same neuron. We examine the consequences of this seeming redundancy using a mathematical model of the crab gastric mill (chewing) network. This network is activated in vitro by the projection neuron MCN1, which elicits a half-center bursting oscillation between the reciprocally-inhibitory neurons LG and Int1. We focus on two neuropeptides which modulate this network, including a MCN1 neurotransmitter and the hormone crustacean cardioactive peptide (CCAP). Both activate the same voltage-gated current (I MI ) in the LG neuron. However, I MI-MCN1 , resulting from MCN1 released neuropeptide, has phasic dynamics in its maximal conductance due to LG presynaptic inhibition of MCN1, while I MI-CCAP retains the same maximal conductance in both phases of the gastric mill rhythm. Separation of time scales allows us to produce a 2D model from which phase plane analysis shows that, as in the biological system, I MI-MCN1 and I MI-CCAP primarily influence the durations of opposing phases of this rhythm. Furthermore, I MI-MCN1 influences the rhythmic output in a manner similar to the Int1-to-LG synapse, whereas I MI-CCAP has an influence similar to the LG-to-Int1 synapse. These results show that distinct neuromodulators which target the same voltage-gated ion channel in the same network neuron can nevertheless produce distinct effects at the network level, providing divergent neuromodulator actions on network activity.

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Acknowledgments

Supported by NIH MH060605 (FN), Kenny Fund Fellowship (NK), and NIH NS029436 (MPN).

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Authors and Affiliations

  1. Department of Mathematics, Saint Peter’s University, Jersey City, NJ, 07306, USA

    Nickolas Kintos

  2. Department of Neuroscience, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA

    Michael P. Nusbaum

  3. Federated Department of Biological Sciences, New Jersey Institute of Technology and Rutgers University, 323 Martin Luther King Blvd., Newark, NJ, 07102, USA

    Farzan Nadim

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  1. Nickolas Kintos
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  2. Michael P. Nusbaum
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  3. Farzan Nadim
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Correspondence to Farzan Nadim.

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Action Editor: Frances K. Skinner

Appendix

Appendix

Below is the program code for the xpp file associated with the model. The changes in parameter values needed for some of the figures are listed as comments in the code.

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Kintos, N., Nusbaum, M.P. & Nadim, F. Convergent neuromodulation onto a network neuron can have divergent effects at the network level. J Comput Neurosci 40, 113–135 (2016). https://doi.org/10.1007/s10827-015-0587-z

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