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Modeling Pacemaking, Bursting, and Depolarization Block in Midbrain Dopamine Neurons

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Dopaminergic System Function and Dysfunction: Experimental Approaches

Part of the book series: Neuromethods ((NM,volume 193))

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Abstract

Here we present methodology to simulate the electrical activity of dopamine neurons by using a freely available software package to numerically integrate a set of coupled nonlinear equations that describe the equivalent circuit that generates the membrane potential, the nonlinear dynamics of channel gating, and a material balance on Ca2+ ions. The general methodology is conductance-based single-neuron computational models. We begin with Hodgkin-Huxley (H-H)-type conductance-based single-compartment models of pacemaking in vitro, which is described mathematically as a limit cycle. We illustrate phase plane methods to gain insight into this activity. Next, we address modeling rhythmic bursting activity. To illustrate that the methodology can be extended beyond the H-H formalism in which activation and inactivation gates operate independently of each other, we include a Markov model of a K+ channel in which they are dependent on each other. We then add random synaptic input to the model to illustrate the hypothesized balanced state in dopamine neurons, which is quite distinct from the balanced state of neocortical pyramidal neurons. We use this model to explain transient bursts and pauses. A major advantage of models is that parameter sweeps can be conducted quickly to determine the robustness of predicted activity. Finally, we move to a multi-compartmental model that captures the full morphology of a dopamine neuron to illustrate the role of the axon initial segment (AIS) in action potential initiation.

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Authors and Affiliations

  1. Department of Cell Biology and Anatomy, School of Medicine, Louisiana State Health Sciences Center-New Orleans, New Orleans, LA, USA

    Christopher Knowlton & Carmen C. Canavier

Authors
  1. Christopher Knowlton
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  2. Carmen C. Canavier
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Correspondence to Carmen C. Canavier .

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Editors and Affiliations

  1. Escuela de Química y Farmacia y Centro Interdisciplinario de Neurociencia, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago, Chile

    José Antonio Fuentealba-Evans

  2. Departamento de Anatomía Normal, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

    Pablo Henny

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Knowlton, C., Canavier, C.C. (2023). Modeling Pacemaking, Bursting, and Depolarization Block in Midbrain Dopamine Neurons. In: Fuentealba-Evans, J.A., Henny, P. (eds) Dopaminergic System Function and Dysfunction: Experimental Approaches. Neuromethods, vol 193. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2799-0_5

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  • DOI: https://doi.org/10.1007/978-1-0716-2799-0_5

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2798-3

  • Online ISBN: 978-1-0716-2799-0

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