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Original Article

Korean J Physiol Pharmacol 2024; 28(2): 165-181

Published online March 1, 2024

Copyright © Korean J Physiol Pharmacol.

Somatodendritic organization of pacemaker activity in midbrain dopamine neurons

Jinyoung Jang#, Shin Hye Kim#, Ki Bum Um, Hyun Jin Kim, and Myoung Kyu Park*

Department of Physiology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea

Correspondence to:Myoung Kyu Park
E-mail: mkpark@

#These authors contributed equally to this work.

Author contributions: J.J., S.H.K., and M.K.P. participated in conception and experimental design. J.J. and S.H.K. carried out the electrical and twophoton confocal imaging experiments and J.J. and K.B.U. prepared immunocytochemistry data. J.J., S.H.K., H.J.K., and M.K.P. participated in analysis of electrophysiological data and preparation of the figures. J.J. and M.K.P. wrote and revised the manuscript and J.J., S.H.K., M.K.P., and H.J.K. helped preparation of the manuscript and figures. All authors reviewed the manuscript.

Received: December 21, 2023; Revised: January 8, 2024; Accepted: January 8, 2024


The slow and regular pacemaking activity of midbrain dopamine (DA) neurons requires proper spatial organization of the excitable elements between the soma and dendritic compartments, but the somatodendritic organization is not clear. Here, we show that the dynamic interaction between the soma and multiple proximal dendritic compartments (PDCs) generates the slow pacemaking activity in DA neurons. In multipolar DA neurons, spontaneous action potentials (sAPs) consistently originate from the axon-bearing dendrite. However, when the axon initial segment was disabled, sAPs emerge randomly from various primary PDCs, indicating that multiple PDCs drive pacemaking. Ca2+ measurements and local stimulation/perturbation experiments suggest that the soma serves as a stably-oscillating inertial compartment, while multiple PDCs exhibit stochastic fluctuations and high excitability. Despite the stochastic and excitable nature of PDCs, their activities are balanced by the large centrally-connected inertial soma, resulting in the slow synchronized pacemaking rhythm. Furthermore, our electrophysiological experiments indicate that the soma and PDCs, with distinct characteristics, play different roles in glutamate- induced burst-pause firing patterns. Excitable PDCs mediate excitatory burst responses to glutamate, while the large inertial soma determines inhibitory pause responses to glutamate. Therefore, we could conclude that this somatodendritic organization serves as a common foundation for both pacemaker activity and evoked firing patterns in midbrain DA neurons.

Keywords: Calcium signaling, Dopaminergic neurons, Glutamatergic synapse, Pacemaking, Substantia nigra