REVIEW article
Front. Cell. Neurosci.
Sec. Cellular Neurophysiology
Volume 19 - 2025 | doi: 10.3389/fncel.2025.1681044
This article is part of the Research TopicAxon Neurobiology: Updates in Functional and Structural DynamicsView all 5 articles
Intrinsic and synaptic regulation of axonal excitability in dopaminergic neurons
Provisionally accepted
- 1University of Michigan Neuroscience Graduate Program, Ann Arbor, United States
- 2University of Michigan Department of Molecular Cellular and Developmental Biology, Ann Arbor, United States
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Dopamine released from the axon terminals of dopaminergic neurons is central to behaviors like reward learning and complex motor output. The dynamic control of dopamine release canonically occurs through two main mechanisms: the modulation of somatic excitability and the regulation of vesicular release at presynaptic boutons. However, there is also a third mechanism: the precise and local control of axonal excitability. Together, these three mechanisms control the amplitude and timing of dopamine release from terminal axons. In this review, we examine the intrinsic properties and dynamic modulation of dopaminergic axons. First, we will examine their intrinsic properties, including membrane biophysics and morphological features. Second, we will focus on the modulation of axonal excitability through receptor signaling. Finally, we will review how drugs of abuse directly influence axonal physiology, and how axonal excitability influences the progression and etiology of Parkinson's disease. Through this review we hope to highlight the important role that modulation of axonal excitability plays in controlling dopamine release, beyond action potential propagation.
Keywords: Dopamine, Axons, neurophyiology, Ion Channels, modulation, excitability, receptor signaling
Received: 06 Aug 2025; Accepted: 16 Oct 2025.
Copyright: © 2025 Seddon and Kramer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Paul F. Kramer, pfkramer@umich.edu
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