The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Somatodendritic organization of pacemaker activity in midbrain dopamine neurons

  • Jinyoung Jang (Department of Physiology, Sungkyunkwan University School of Medicine) ;
  • Shin Hye Kim (Department of Physiology, Sungkyunkwan University School of Medicine) ;
  • Ki Bum Um (Department of Physiology, Sungkyunkwan University School of Medicine) ;
  • Hyun Jin Kim (Department of Physiology, Sungkyunkwan University School of Medicine) ;
  • Myoung Kyu Park (Department of Physiology, Sungkyunkwan University School of Medicine)
  • Received : 2023.12.21
  • Accepted : 2024.01.08
  • Published : 2024.03.01
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Abstract

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

Acknowledgement

This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI13C1793) and by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2017R1A2B3005656 and 2022R1A2C2009159).

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