Mechanism of manganese dysregulation of dopamine neuronal activity

Min Lin, Luis M. Colon-Perez, Danielle O. Sambo, Douglas R. Miller, Joseph J. Lebowitz, Felix Jimenez-Rondan, Robert J. Cousins, Nicole Horenstein, Tolunay Beker Aydemir, Marcelo Febo, Habibeh Khoshbouei

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Manganese exposure produces Parkinson's-like neurologic symptoms, suggesting a selective dysregulation of dopamine transmission. It is unknown, however, how manganese accumulates in dopaminergic brain regions or how it regulates the activity of dopamine neurons. Our in vivo studies in male C57BLJ mice suggest that manganese accumulates in dopamine neurons of the VTA and substantia nigra via nifedipine-sensitive Ca2+channels. Manganese produces a Ca2+channel-mediated current, which increases neurotransmitter release and rhythmic firing activity of dopamine neurons. These increases are prevented by blockade of Ca2+channels and depend on downstream recruitment of Ca2+-activated potassium channels to the plasma membrane. These findings demonstrate the mechanism of manganese-induced dysfunction of dopamine neurons, and reveal a potential therapeutic target to attenuate manganese-induced impairment of dopamine transmission.

Original languageEnglish
Pages (from-to)5871-5891
Number of pages21
JournalJournal of Neuroscience
Issue number30
StatePublished - 22 Jul 2020


  • Dopamine Neurons
  • L-Type Calcium Channel
  • Manganese
  • Parkinson's Disease
  • Synaptic Transmission


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