Dopaminergic System Function and Dysfunction: Experimental Approaches

Document Type

Book Chapter

Publication Date

12-8-2022

Publication Title

Neuromethods

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.

First Page

101

Last Page

119

Volume

193

Chapter Title

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

Publisher

Humana

Comments

Volume 193

ISBN

978-1-0716-2798-3

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